Teachers' ability to handle race-sensitive issues directly determines the sense of belonging among minority ethnic students. Although many teachers have the intention to help students, they lack a deep understanding of racial inequality. Eventually, they end up becoming the executors of the hidden curriculum and hurting the students who actually need support.

When I first went abroad to study, in order not to be regarded as an outlier, I deliberately imitated the speaking tones and classroom interaction styles of local classmates. I even dared not question the professors' viewpoints for fear of being labeled as disrespectful to authority. Only now do I realize that this was actually conforming to the conformist demands of the mainstream culture.

This gap can create a vicious cycle: poor reading skills in primary school make it harder to understand texts in middle school, and when facing academic reading in university, the struggle becomes even greater. It’s like falling behind one step and then lagging further behind at every subsequent step.

This kind of selective evaluation hurts people more than the lack of resources, because it will gradually make students deny their own values and feel that their inherent advantages are useless.

comparing himself to God

• not in current state of regret
• being on the cusp of creating a new living form
• he’s having a hard time handling this new found power

• a pause to give moment of reaction
• Waldman kinda saying “you did what”

• getting to the scientific core
• early example of science fiction

I find the simplification of data very interesting, because that is an aspect of coding that I have never really considered before. Even in our everyday lives, information is being simplified in a way that is easy for people to process and digest, so why should coding be any different? In particular, the examples of the complexity of even simple questions like "what country are you from" was interesting because I had never really considered the complexities behind questions like that.

• grand, rhetorical vision of science which Victor feeds on

• making small discoveries at a time

• fictions

Language can be learned gradually, but the loneliness of feeling "unseen" causes students to gradually give up on integrating into the community. Educational equity is not just about providing the same courses; it is more about offering tailored support to students with different needs. Otherwise, the system will only amplify existing gaps.

Students who have long received training in critical writing and in-class debates can quickly keep up with professors' thinking pace. In contrast, students from ordinary families in developing countries — even if they are fluent in the language — often fall slightly behind in essay structure and expression of ideas due to a lack of such early training. Over time, a GPA gap will naturally emerge. This shows that equal classrooms do not equate to equal outcomes.

Some of my classmates in the past, because they were unfamiliar with the faculty evaluation system, ended up enrolling in low-rated courses with unbalanced difficulty levels — which directly affected their GPAs. The so-called "freedom of choice" is essentially a privilege of those with more resources.

Ethnic minority students face such a dilemma: their behavioral habits and linguistic styles do not align with the prevailing dominant cultural capital of the school. Even if they meet the ability requirements, their potential is still likely to be underestimated. Over the long term, this leads students to develop self-doubt and eventually give up opportunities for advanced courses.

African American students are concentrated in lower-level courses, while white students dominate upper-level ones — as if students’ futures have been predetermined starting from the 9th grade. Even more worrying is that this stratification is not based on ability assessments; instead, it stems from stereotypes about ethnic minorities and resource deprivation. This is harder to break than direct discrimination, because it disguises itself as the result of personal choice.

• compact metaphor
• beginning of his passion
• hidden well below the ground but becomes a river (destroying force)
• in the book weather begins to show what type of state he is in

Have no homologs?

She is jealous of Dee. She believes Dee is perfect and compares her to Maggie who isn’t as smart as Dee.

The image of a smiling woman from Antilles, standing between two bushels of bananas, was the first image used in 1912 to advertise Banania, a banana-flavored chocolate drink most widely distributed in France. Three years later, she was replaced with a smiling African man holding a spoon of the drink like a child and accompanied with the slogan, “Y’a bon” — a phrase of pidgin French that translates to, “It’s good.” https://hyperallergic.com/380053/the-racist-caricatures-of-african-soldiers-that-soothed-french-colonial-anxieties/

Not everything we see is true and having the motivation and will to fact check resources and question things you might have previously taken at face value is a good thing, it feeds your curiosity and you ability to do research and interpret evidence on your own.

Having the ability to have confidence in ones self is extremely important. Having to confidence to try new things to expand your learning and mindset allows you to broaden your horizons in a new way.

Having this mindset is extremely important especially when looking at data. Being able to step back and have an unbiased opinion will often lead to better and more constant results even outside of scientific investigations.

Being able to more deeply engage with the material allows the reader to optimize the amount of information they gain from the material.

I think this is one of the best ways of thinking because you are skeptical of everything but you are looking for evidence of why it could be true or it could be false unlike conspiracy theories that are based on just speculation. This is like a conspiracy theory mindset but with an idea of looking for evidence.

This really reminds me of a book called Tiny Experiments: How to Live Freely in a Goal-Obsessed World where it's all about trying to live in a scientific mindset

This point directly related to the ways that black americans have historically not had contorl over where they live due to redlining

Goes back to the point that natural disasters are actually human disasters

Example of vulnerable individuals being harmed and killed at the highest rates during natural disasters

Climate change doesn't exist in a vaccum. It is mapped onto existing disparities and enhances them

This study is important because understanding the aspects that contribute to vulnerabilities to extreme weather events can reduce harm and mortality

purpose of focusing on these themes and disciplines

This paper is interdisiplinary

Themes to understand social aspects of vulnerability

Key term: Definition of vulnerability

Main question

Initial understanding of climate change failed tot ake into account the social factors that contribute to ones or a communitites vulnerability

I wish this was still more popular! Bring back blogging about random things. I think it would eliminate a lot of bad things about social media.

The fear of politics interfering with the fundamental of teaching has brainwashed all educators. Teachers often tip toe around to be safe rather than teach to educate the future

There is not a formula that leads us to the promised land. Great teachers can adapt to different learning g types students may have. Their ability to work with the students at different paces is valuable

for - key insight - there are other spaces where beings live that we cannot visualize - Michael Levin

for - invalid assumptions - Michael Levin - finding counterexamples that invalidate long standing general principle

for - paradigm shift - outdated framework - Michael Levin

for - comparison - causation - engineer vs philosopher - Michael Levin

for - adjacency - mathematics - physical reality - Descarte - Micahael Levin

for - causation - Michael Levin

for - quote - patterns are goal states intelligent systems are pursuing - Michael Levin

for - progress traps - perspective - Michael Levin

for - adjacency - 4E science - platonic space

Draws from two rural communtities in british columbia, canada

Central Argument

What is the difference errant annelids and sedentary annelids?

Why is torsion important for gastropods?

What are some physiologic characteristics that make platyhelminthes unique?

The claim that poor families are to blame is completely false. Education is the great equalizer and all families should be presented with fair opportunities to learn

This quote shows irony as schools promote to teach inequality, but rather reduce it through their actions

This line highlights the high prevalence of malnutrition among elderly residents in institutions, with estimates of between one-fifth to more than half being malnourished, depending on measurement methods. This helps to explain why the study looks at how nutritional status relates to cognition, functional capacity, and polypharmacy. If malnutrition is common, the consequences can be severe.

Cool that graffiti has kind of changed in a way where people will tag pretty much whatever just with their name when it used to be more informative. That informative part of street art I think it has been taken by flyers or posters that will have updates or messages. But more and more these days I am seeing explicitly politic graffiti around witch seems a bit closer to it's original use.

This is strikingly similar to the legal and cultural "meshwork" of the Salem Witch Trials, in which the judicial system, Puritan religion, and community norms all converged to shape human behaviour and thought. The legal procedures and moral frameworks of the trials had their own agency, and when invoked, they led human activity almost mechanically. Just as built-in assumptions impact users' judgments, Salem's laws and beliefs limited what participants might perceive as "truth," essentially transforming the system into a cognitive agent.

This is nothing but the truth! No matter how I frame the artworks through Kirta, in some way, shape or form, my own personal biases and touch get employed onto the pieces. Although I can claim that I will not try to separate any form of truth from the narratives featured in my project, just my personal decision on what to animate and what not to, changes the narrative into a personalized one. I have to be careful with my decision-making and what I choose to bring to life.

This line captures a central paradox: while everyone is promised equal opportunity, outcomes still depend heavily on inherited advantages like wealth or school quality.

This opening clearly frames the American Dream as both individualistic and collective. It emphasizes opportunity and self-determination, but also assumes equal access—which is idealistic. It makes me wonder: how realistic is this belief in equal opportunity given the current education system’s inequalities?

There is a complaint from the FTC alleges that Facebook has not developed innovative mobile features for its network, Facebook instead resorted to an illegal buy-or-bury scheme to maintain its dominance over the market. It unlawfully acquired innovative competitors with popular mobile features that succeeded where Facebook’s own offerings fell flat or fell apart witch is illegal. And so the FTC goes after Facebook

This article tells about how Aza Raskin, the inventor of "infinite scrolling", expressed regret for the social impact his design had caused. After reading it, I was deeply impressed because it made the concept of "technology neutrality" highly questionable. In the fifth chapter, it mentions how social media makes people addicted and constantly refreshes, and this report precisely reveals that the designers behind it also realized the severity of the problem. I think this source makes me reflect: the "convenience" of many social functions is actually quietly taking away our attention. Raskin's remorse reminds us that design is not only a matter of technical choice, but also an ethical choice. Developers need to realize that they are shaping people's behaviors, not just their user experience.

I would say scrolling is the greatest invention in modern social media, especially for short videos. In the past, people usually chose the video they would like to watch based on the cover page and the title. It's somewhat related to consequentialism, as users have a purpose or expectations before they click into a video. However, the scrolling algorithm is giving users a kind of 'surprise'. The user will never know what video will be the next one, so they will continue to scroll down to find something new and satisfy the sense of opening a mystery box. The scrolling algorithm kept users on their social media for a significant time, but the feature of short videos is lowering the quality of information that the user will receive.

Reading [e33], the inventor apologizes for infinite scroll because it removes stopping points and lengthens use. I propose an ethical design rule: build in “natural stops”—page ends, session timers, and a one-tap “take a break” card—enabled by default and easy to keep on. Platforms should have to justify any removal of these stops.

This article is mainly about politicians being accused of having secret deals or engaging improper and shady behavior to obtain more reputation and win their elections. It was interesting that conspiracy theories was not an invention, people were already spreading them 200 years ago. It just shows that human nature does not change.

I wanna end on a positive note and create an affirmation for myself and work for the future. I have the capability to learn a new program and create an animation! As long as I continue with the mindset of growth and learning, I can do anything!

When I read this sentence, I realized that I almost entirely live in the Web 2.0 world. For me, the Internet has always been interactive, open, and a place where everyone can express themselves. But when I look back, this freedom of "everyone can speak" has also brought a lot of anxiety, such as the need to constantly update and gain attention, otherwise it feels like being "ignored by the network". I think this section reminds me to think: Is the "interaction" of social media about expressing oneself or being forced to participate? It makes me better understand why some people start "digital decluttering", which might be a way to regain control.

like shes getting interrupted by voices in her head

* Fell off = desaparecer.

* Get = traer / conseguir

* Trouble = problema.

* Heavily = ampliamente. * covering = cubriendo. * Rise= aumentando

* That = así. * Whole = todo * Counter Measure = contramedida.

lmao

acknowledges God's heirarchy of man (accepts?) but still places responsibility on the man

do it, do it scared

reaching the level of attainable piousness relies more on internal mechanisms-- reading the Bible alone does not make you holy

speaking through the voice of god?

It is important to decipher what everything will be used for in the project, so as not to waste my time on things that are not as necessary. Maybe there are certain components to hone in on for a more interesting animation. The organization of information is just as important as the final project. I do not want to make this process of animating on Krita any harder than it has to be, so creating a storyboard, preestablished paragraphs, or a template to follow for the organization of information.

https://www.youtube.com/watch?v=T-ibUVMh9XE

See this video for more information on how to do this.

1. “In labour it is the particular characteristic of my individuality that is affirmed”

Normally, under capitalism, your work doesn’t reflect who you really are — it’s just a task to earn money.

But in true human labour, your work expresses your unique skills, talents, and personality — your individuality.

So, when you work freely and creatively, you are affirming yourself as a unique person.

1. “Because it is my individual life that is affirmed”

Labour becomes meaningful because it reflects your life and your choices.

Your work is no longer just a job you must do to survive; it expresses who you are.

Think of it like painting a picture, writing a story, or making something with your own ideas — your work is a piece of yourself.

freely (creative expression)

strenghten yourself and other person

The object is “nothing” outside consciousness.

Hegel says that objects, as we experience them, are really just reflections of our own consciousness.

They have no independent reality apart from how we know them. In that sense, they are “null” or “nothing” on their own.

This “nothingness” is actually meaningful.

Even though objects are “null,” this nullity helps consciousness understand itself.

By recognizing that the object is just a reflection of itself, consciousness confirms its own nature. So the object’s nullity has a positive role: it’s a mirror for self-awareness.

Consciousness only exists in knowing.

For Hegel, consciousness is defined by knowing.

Something exists “for consciousness” only if consciousness knows it. That’s why the object’s reality is tied to our awareness of it.

Objects are really “self-alienation.”

When we encounter an object, it seems separate from us. But Hegel says this separateness is illusory.

The object is just consciousness seeing itself as “other,” so in relating to the object, consciousness is interacting with itself in disguise.

Consciousness overcomes this alienation.

Finally, consciousness realizes that the object is only a reflection of itself.

It can “take back” this alienation—seeing that what appeared to be external is actually part of itself.

In this way, consciousness becomes “at home” with the object and with itself.

COME BACK TO THIS PARA

Should only 87116010 be kept for E-bikes in the EU?

The creation and research for my project will follow a similar list of components. 1) Locate and find the data: I have to select artworks that I believe are rich in narrative, to allow for an expressive animation. 2) Research and collect: Find as much information about the narrative as possible, and collect as much context as I can. The more the better, as it brings more content for the story. 3) Analyze the Data and Visuals: What parts are the best for animation? What would bring the narrative to life the most? 4) Communicating the Story in the Data: Using Krita and bringing the project to light.

Date Published: May 2020, by Monica Fraga

COVID era

First generation have higher % of food insecurity than regular

accepting only/mostly women of higher nobility to "assign to their proper place"?

insinuating her as the higher order?

My project ties into the themes of digital humanities as well. Digital humanities is how we apply digital technologies to study culture, history and the arts. Because my project requires a lot of research with these 3 categories, my work with Krita will integrate with the concept of digital humanities with archeology.

I observe that the journal talks about how Lewis and Clark and the people who accompanied them had decided to set out early and passed the front of the island opposite to where they had camped last night, they then had breakfast on the mouth of a large creek on the south side. They had set their course to being north west and a short distance from where they were at the mouth of the creek there were paintings and carving in the limestone rock with white red and blue flint of good quality. In which the native Americans had taken a great deal of. I interpret this as a way for the author to make a detailed entry and record of their experiences and by giving specific land marks and other details like their course the author is able to make it easier for someone to retrace their steps if they were to. I can connect this to the tertiary source in how it talks about how the main objectives of this journey were to gain geographic and scientific information on the land and its plant and animal life. A second goal was also in the diplomatic and commercial interest of the United States who wanted to find a water route to the pacific in order to gain a stronger position in the fur trade. This is seen in the highlighted section in how the author notes how the land is by noting the creek and the landmark of the paintings on the rock. Context: Jefferson had wanted to expand the united states and compete with Canada in the fur trade. He had wanted to do so earlier than the expedition of Lewis and Clark and attempted so before the Louisiana purchase in 1803. However the expedition came to fruition following the purchase in which Lewis and Clark along with their group were tasked with exploring the vast recently purchased land.

Так математические формулы тоже обобщают.

из набора аргументов можно начать предсказывать сложные структуры. удивительно как создав обёртку, можно начать предсказывать большое количество деталей.

Social media like bilibili were using this strategy (bullet screen) to gather more and more users. Or, in other words, it was a special feature that allowed bilibili to stand out from other video-based social media platforms. The bullet screen is forming a culture and attracting users; however, the way of informal connections may cause some problems. For example, people could easily argue about a specific or minor issue because almost no punishment will be imposed, and people from the two sides will never meet each other offline. Sometimes it's ridiculous that two people who don't even know each other will become enemies online.

I support adding "friendly friction" to the UI. The pop-up before retweeting makes me hesitant. I also suggest offering adjustable friction levels (read timers, cooldowns for late-night posts). This would reduce impulsive spreading while still maintaining freedom of choice. Do you agree?

I think it is based on the users' intention. If they want more privacy, they could just provide their name. But for working apps like Linkin or dating apps, it would be more appropriate to provide more information such as age, school degree or working status.

The Greeks mostly saw Africa as opposites to them, they saw the climate was vastly differant, they saw that the social constructs were different and also viewed them as barbaric.

Quality Management Plan

The Quality Management Plan defines how quality will be managed throughout the project. It ensures deliverables meet requirements and stakeholder expectations.

It includes:

• Quality standards & practices – which standards apply (e.g., ISO, company standards).
• Roles and responsibilities – who handles quality tasks and when.
• Processes and procedures – how quality will be checked, controlled, and improved.
• Decision reviews – confirming earlier quality-related choices are still valid.
• Quality meetings and reports – what will be discussed and documented.
• Quality metrics – how quality performance will be measured.
• Measurement points – which deliverables will be evaluated and when.

Quality Metrics

Quality metrics are specific, measurable indicators used to evaluate how well the project is performing against its quality goals. They are defined in advance so performance can be tracked objectively.

Examples:

• Number of change requests → shows how well the project was planned.
• Resource utilization variance → checks if resources are being used efficiently.
• Number of items that fail inspection → measures product or process quality.
• Number of software bugs → tracks defect rate for development projects.

✅ In short: The Quality Management Plan explains how quality will be ensured. Quality Metrics specify what will be measured to confirm that quality.

Reserve Analysis

A technique used to identify and include extra time or money (reserves) in the project budget or schedule to handle risks and uncertainties.

Types of Reserves:

1. Contingency Reserve (for Known Unknowns)

• Covers identified risks that might happen (e.g., delays, rework).
• Usually a percentage of the project budget or estimated using quantitative risk analysis.
• Controlled by: the project manager.
• Example: Adding 10% extra budget for possible material price increases.

2. Management Reserve (for Unknown Unknowns)

• Covers unforeseen risks — things you didn’t or couldn’t plan for.
• Not part of the cost baseline (released only with approval).
• Controlled by: senior management or sponsor.
• Example: Unexpected regulation change requiring redesign.

Cost of Quality (COQ)

Refers to the total cost of ensuring quality in a project. It includes:

• Cost of conformance – investment to prevent defects (e.g., training, inspections, testing).
• Cost of non-conformance – cost after defects occur (e.g., rework, warranty claims, loss of reputation).

✅ In short:

Reserve Analysis adds planned buffers for uncertainty — Contingency = known risks, Management = unknown risks, and COQ balances prevention costs vs. failure costs to ensure quality.

Parametric Estimating Technique:

Parametric Estimating uses statistical or mathematical relationships between variables (like cost per unit, time per task, or resources per square meter) to estimate project cost or duration.

It works best when activities are known, repeatable, and standardized, with reliable historical data to base calculations on.

✅ Strengths:

• More accurate than rough estimates since it’s data-based.
• Less variance because similar operations produce consistent results.

⚠️ Weaknesses:

• Assumes standard activities — doesn’t work well for unique or innovative projects.
• Requires historical data — accuracy depends on how relevant and available that data is.

✅ In short:

Parametric estimating = uses formulas and historical data for standardized work → accurate when data is solid, but limited for new or unique projects.

I agree with this because there is many tourists blogging about Africa when they don't know anything about their culture and are simply sharing their biased point of view.

These stay consistent with videos I see online that are people asking for help and tourists going around filming people not translating their culture.

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Reply to the reviewers

We thank the referees for taking time to review our manuscript. These reviews are positive, highlighting the novelty of our findings. The majority of comments are cosmetic, and we have added data in response to some technical points. We feel that some of the additional experiments proposed would not add significant methodological depth, and cross-commenting suggests that our referees agree. At present we are attempting antibody staining to quantify Tk peptide retention in the midgut, as per suggestion by reviewer #2.

We enclose our point-by-point response to each referee's points, below.

__Reviewer #1 __

• Can the authors state in the figure legends the numbers of flies used for each lifespan and whether replicates have been done?

• We have incorporated the requested information into legends for lifespan experiments.

• Do the interventions shorten lifespan relative to the axenic cohort? Or do they prevent lifespan extension by axenic conditions? Both statements are valid, and the authors need to be consistent in which one they use to avoid confusing the reader.

• We read these statements differently. The only experiment in which a genetic intervention prevented lifespan extension by axenic conditions is neuronal TkR86C knockdown (Figure 6B-C). Otherwise, microbiota shortened lifespan relative to axenic conditions, and genetic knockdowns extend blocked this effect (e.g. see lines 131-133). We have ensured that the framing is consistent throughout, with text edited at lines 198-199, 298-299, 311-312, 345-347, 408-409, 424-425, 450, 497-503.

• TkRNAi consistently reduces lipid levels in axenic flies (Figs 2E, 3D), essentially phenocopying the loss of lipid stores seen in control conventionally reared (CR) flies relative to control axenic. This suggests that the previously reported role of Tk in lipid storage - demonstrated through increased lipid levels in TkRNAi flies (Song et al (2014) Cell Rep 9(1): 40) - is dependent on the microbiota. In the absence of the microbiota TkRNAi reduces lipid levels. The lack of acknowledgement of this in the text is confusing

• We have added text at lines 219-222 to address this point. We agree that this effect is hard to interpret biologically, since expressing RNAi in axenics has no additional effect on Tk expression (Figure S7). Consequently we can only interpret this unexpected effect as a possible off-target effect of RU feeding on TAG, specific to axenic flies. However, this possibility does not void our conclusion, because an off-target dimunition of TAG cannot explain why CR flies accumulate TAG following TkRNAi We hope that our added text clarifies.

• *I have struggled to follow the authors logic in ablating the IPCs and feel a clear statement on what they expected the outcome to be would help the reader. *

• We have added the requested statement at lines 423-424, explaining that we expected the IPC ablation to render flies constitutively long-lived and non-responsive to A pomorum.

• *Can the authors clarify their logic in concluding a role for insulin signalling, and qualify this conclusion with appropriate consideration of alternative hypotheses? *

• We have added our logic at lines 449-454. In brief, we conclude involvement for insulin signalling because FoxO mutant lifespan does not respond to TkRNAi, and diminishes the lifespan-shortening effect of * pomorum*. However, we cannot state that the effects are direct because we do not have data that mechanistically connects Tk/TkR99D signalling directly in insulin-producing cells. The current evidence is most consistent with insulin signalling priming responses to microbiota/Tk/TkR99D, as per the newly-added text.

• Typographical errors

• We have remedied the highlighted errors, at lines 128-140.

• I'd encourage the authors to provide lifespan plots that enable comparison between all conditions

• We have plotted our figures in faceted boxes, because the number of survival curves that would need to be presented on the same axis (e.g. 16 for Figure 5) would not be intellegible. However we have ensured that axes on faceted plots are equivalent and with grid lines for comparison. Moreover, our approach using statistical coefficients (EMMs) enables direct quantitative comparison of the differences among conditions.

Reviewer #2

• Not…essential for publication…is it possible to look at Tk protein levels?

• We have acquired a small amount of anti-TK antibody and we will attempt to immunostain guts associated with * pomorum and L. brevis*. We are also attempting the equivalent experiment in mouse colon reared with/without a defined microbiota. These experiments are ongoing, but we note that the referee feels that the manuscript is a publishable unit whether these stainings succeed or not.

• it would be good to show that the bacterial levels are not impacted [by TkRNAi]

• We have quantified CFUs in CR flies upon ubiquitous TkRNAi (Figure S5), finding that the RNAi does not affect bacterial load. New text at lines 138-139 articulates this point.

• The effect of Tk RNAi on TAG is opposite in CR and Ax or CR and Ap flies, and the knockdown shows an effect in either case (Figure 2E, Figure 3D). Why is this?

• As per response to Reviewer #1, we have added text at lines 219-222 to address this point.

• Is it possible to perform at least one lifespan repeat with the other Tk RNAi line mentioned?

• We have added another experiment showing longevity upon knockdown in conventional flies, using an independent TkRNAi line (Figure S3).

• Is it possible that this driver is simply not resulting in an efficient KD of the receptor? I would be inclined to check this

• This comment relates to Figure 7G. We do see an effect of the knockdown in this experiment, so we believe that the knockdown is effective. However the direction of response is not consistent with our hypothesis so the experiment is not informative about the role of these cells. We therefore feel there is little to be gained by testing efficacy of knockdown, which would also be technically challenging because the cells are a small population in a larger tissue which expresses the same transcripts elsewhere (i.e. necessitating FISH).

• Would it be possible to use antibodies for acetylated histones?

• The comment relates to Figure 4C-E. The proposed studies would be a significant amount of work because, to our knowledge, the specific histone marks which drive activation in TK+ cells remain unknown. On the other hand, we do not see how this information would enrich the present story, rather such experiments would appear to be the beginning of something new. We therefore agree with Reviewer #1 (in cross-commenting) that this additional work is not justified.

Reviewer #3

• *In Line243, the manuscript states that the reporter activity was not increased in the posterior midgut. However, based on the presented results in Fig4E, there is seemingly not apparent regional specificity. A more detailed explanation is necessary. *

• We thank the reviewer sincerely for their keen eye, which has highlighted an error in the previous version of the figure. In revisiting this figure we have noticed, to our dismay, that the figures for GFP quantification were actually re-plots of the figures for (ac)K quantification. This error led to the discrepancy between statistics and graphics, which thankfully the reviewer noticed. We have revised the figure to remedy our error, and the statistics now match the boxplots and results text.

• Fig1C uses Adh for normalization. Given the high variability of the result, the authors should (1) check whether Adh expression levels changed via bacterial association

• We selected Adh on the basis of our RNAseq analysis, which showed it was not different between AX and CV guts, whereas many commonly-used “housekeeping” genes were. We have now added a plot to demonstrate (Figure S2).

• The statement in Line 82 that EEs express 14 peptide hormones should be supported with an appropriate reference

• We have added the requested reference (Hung et al, 2020) at line 86.

• Tk+ EEC activity should be assessed directly, rather than relying solely on transcript levels. Approaches such as CaLexA or GCaMP could be used.

• We agree with reviewers 1-2 (in cross-commenting) that this proposal is non-trivial and not justified by the additional insight that would be gained. As described above, we are attempting to immunostain Tk, which if successful will provide a third line of evidence for regulation of Tk+ cells. However we note that we already have the strongest possible evidence for a role of these cells via genetic analysis (Figure 5).

• While the difficulty of maintaining lifelong axenic conditions is understandable, it may still be feasible to assess the induction of Tk (ie. Tk transcription or EE activity upregulation) by the microbiome on males.

• As the reviewer recognises, maintaining axenic experiments for months on end is not trivial. Given the tendency for males either to simply mirror female responses to lifespan-extending interventions, or to not respond at all, we made the decision in our work to only study females. We have instead emphasised in the manuscript that results are from female flies.

• TkR86C, in addition to TkR99D, may be involved in the A. pomorum-lifespan interaction. Consider revising the title to refer more generally to the "tachykinin receptor" rather than only TkR99D.

• We disagree with this interpretation: the results do not show that TkR86C-RNAi recapitulates the effect of enteric Tk-RNAi. A potentially interesting interaction is apparent, but the data do not support a causal role for TkR86C. A causal role is supported only for TkR99D, knockdown of which recapitulates the longevity of axenic flies and TkRNAi flies. Therefore we feel that our current title is therefore justified by the data, and a more generic version would misrepresent our findings.

• The difference between "aging" and "lifespan" should also be addressed.

• The smurf phenotype is a well-established metric of healthspan. Moreover, lifespan is the leading aggregate measure of ageing. We therefore feel that the use of “ageing” in the title is appropriate.

• If feasible, assessing foxo activation would add mechanistic depth. This could be done by monitoring foxo nuclear localization or measuring the expression levels of downstream target genes.

• Foxo nuclear localisation has already been shown in axenic flies (Shin et al, 2011). We have added text and citation at lines 402-403.

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Referee #3

Evidence, reproducibility and clarity

Summary

Marcu et al. demonstrate a gut-neuron axis that is required for the lifespan-shortening effects mediated by gut bacteria. They show that the presence of commensal bacteria-particularly Acetobacter pomorum-promotes Tk expression in the gut, which then binds to neuronal tachykinin receptors to shorten lifespan. Tk has also recently been reported to extend lifespan via adipokinetic hormone (Akh) signaling (Ahrentløv et al., Nat Metab 7, 2025), but the mechanism here appears distinct. The lifespan shortening by Ap via Tk seems to be partially dependent on foxo and independent of both insulin signaling and Akh-mediated lipid mobilization. Although the detailed mechanistic link to lifespan is not fully resolved, the experiment and its results clearly shows the involvement of the molecules tested. This work adds a valuable dimension to our growing understanding of how gut bacteria influence host longevity. However, there are some points that should be addressed.

1. Tk+ EEC activity should be assessed directly, rather than relying solely on transcript levels. Approaches such as CaLexA or GCaMP could be used.
2. In Line243, the manuscript states that the reporter activity was not increased in the posterior midgut. However, based on the presented results in Fig4E, there is seemingly not apparent regional specificity. A more detailed explanation is necessary.
3. If feasible, assessing foxo activation would add mechanistic depth. This could be done by monitoring foxo nuclear localization or measuring the expression levels of downstream target genes.
4. Fig1C uses Adh for normalization. Given the high variability of the result, the authors should (1) check whether Adh expression levels changed via bacterial association and/or (2) compare the results using different genes as internal standard.
5. While the difficulty of maintaining lifelong axenic conditions is understandable, it may still be feasible to assess the induction of Tk (ie. Tk transcription or EE activity upregulation) by the microbiome on males.
6. We also had some concerns regarding the wording of the title. Fig6B and C suggests that TkR86C, in addition to TkR99D, may be involved in the A. pomorum-lifespan interaction. Consider revising the title to refer more generally to the "tachykinin receptor" rather than only TkR99D. The difference between "aging" and "lifespan" should also be addressed. While the study shows a role for Tk in lifespan, assessment of aging phenotypes (eg. Climbing assay, ISC proliferation) beyond the smurf assay is required to make conclusions about aging.
7. The statement in Line 82 that EEs express 14 peptide hormones should be supported with an appropriate reference, if available.

Referees cross-commenting

I agree with the other reviewers that the study has been done very well and hence additional experiments are not mandatory to be published such as calcium imaging. However, I still believe that testing Tk's elevation by the Ap in males should greatly increase the generality of the finding, no matter what the outcome would be. Too many studies use only females.

Significance

General assessment

The main strength of this study is the careful and extensive lifespan analyses, which convincingly demonstrate the role of gut microbiota in regulating longevity. The authors clarify an important aspect of how microbial factors contribute to lifespan control. The main limitation is that the study primarily confirms the involvement of previously reported signaling pathways, without identifying novel molecular players or previously unrecognized mechanisms of lifespan regulation.

Advance

The lifespan-shortening effect of Acetobacter pomorum (Ap) has been reported previously, as has the lifespan-shortening effect of Tachykinin (Tk). However, this study is the first to link these two factors mechanistically, which represents a significant and original contribution to the field. The advance is primarily mechanistic, providing new insight into how microbial cues converge on host signaling pathways to influence ageing.

Audience

This work will be of particular interest to a specialized audience of basic researchers in ageing biology. It will also attract interest from microbiome researchers who are investigating host-microbe interactions and their physiological consequences. The findings will be useful as a conceptual framework for future mechanistic studies in this area.

Field of expertise

Drosophila ageing, lifespan, microbiome, metabolism

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Referee #2

Evidence, reproducibility and clarity

The main finding of this work is that microbiota impacts lifespan though regulating the expression of a gut hormone (Tk) which in turn acts on its receptor expressed on neurons. This conclusion is robust and based on a number of experimental observation, carefully using techniques in fly genetics and physiology: 1) microbiota regulates Tk expression, 2) lifespan reduction by microbiota is absent when Tk is knocked down in gut (specifically in the EEs), 3) Tk knockdown extends lifespan and this is recapitulated by knockdown of a Tk receptor in neurons. These key conclusions are very convincing. Additional data are presented detailing the relationship between Tk and insulin/IGF signalling and Akh in this context. These are two other important endocrine signalling pathways in flies. The presentation and analysis of the data are excellent.

There are only a few experiments or edits that I would suggest as important to confirm or refine the conclusions of this manuscript. These are:

1. When comparing the effects of microbiota (or single bacterial species) in different genetic backgrounds or experimental conditions, I think it would be good to show that the bacterial levels are not impacted by the other intervention(s). For example, the lifespan results observed in Figure 2A are consistent with Tk acting downstream of the microbes but also with Tk RNAi having an impact on the microbiota itself. I think this simple, additional control could be done for a few key experiments. Similarly, the authors could compare the two bacterial species to see if the differences in their effects come from different ability to colonise the flies.
2. The effect of Tk RNAi on TAG is opposite in CR and Ax or CR and Ap flies, and the knockdown shows an effect in either case (Figure 2E, Figure 3D). Why is this? Better clarification is required.
3. With respect to insulin signalling, all the experiments bar one indicate that insulin is mediating the effects of Tk. The one experiment that does not is using dilpGS to knock down TkR99D. Is it possible that this driver is simply not resulting in an efficient KD of the receptor? I would be inclined to check this, but as a minimum I would be a bit more cautious with the interpretation of these data.
4. Is it possible to perform at least one lifespan repeat with the other Tk RNAi line mentioned? This would further clarify that there are no off-target effects that can account for the phenotypes.

There are a few other experiments that I could suggest as I think they could enrich the current manuscript, but I do not believe they are essential for publication: 5. The manuscript could be extended with a little more biochemical/cell biology analysis. For example, is it possible to look at Tk protein levels, Tk levels in circulation, or even TkR receptor activation or activation of its downstream signalling pathways? Comparing Ax and CR or Ap and CR one would expect to find differences consistent with the model proposed. This would add depth to the genetic analysis already conducted. Similarly, for insulin signalling - would it be possible to use some readout of the pathway activity and compare between Ax and CR or Ap and CR? 6. The authors use a pan-acetyl-K antibody but are specifically interested in acetylated histones. Would it be possible to use antibodies for acetylated histones? This would have the added benefit that one can confirm the changes are not in the levels of histones themselves. 7. I think the presentation of the results could be tightened a bit, with fewer sections and one figure per section.

Referees cross-commenting

Reviewer 1

I generally agree with this reviewer but for

"I'm convinced by the data showing that FOXO is required for TkRNAi to prevent lifespan shortening by Ap, but FOXO doesn't only respond to insulin signalling and can't be taken by itself to indicate a role for insulin signalling which the authors appear to do here."

To the best of my knowledge, Foxo has only been shown to be required for lifespan extension/modulation by a reduction in insulin-like signalling. I.e. it does respond to other pathways but this is the only one where Foxo activity is known to modulate lifespan.

Reviewer 3

I agree with reviewer 1 that point raised under (1) does not appear strictly required for the conclusions of the manuscript.

Both reviewers 1 and 3:

I have a different take on the results of experiments where IPCs are manipulated. To me, Figure 7D and E show that ablating the IPCs removes the difference between Ax and Ap i.e. the IPCs are involved and insulin-like signalling is likely involved. The fact that RNAi against the TKR99D receptor does not have the same effect, does not matter (the sensing could happen in different neurons). Similarly, dilp expression is only a minor readout of what is happening with insulin-like signalling - dilps are controlled at the level of secretion.

However, I would be happy for the authors to present different arguments and make a reasonable conclusion, which may differ from mine. But I think the arguments I present above should be taken into account.

Significance

The main contribution of this manuscript is the identification of a mechanism that links the microbiota to lifespan. This is very exciting and topical for several reasons:

1) The microbiota is very important for overall health but it is still unclear how. Studying the interaction between microbiota and health is an emerging, growing field, and one that has attracted a lot of interest, but one that is often lacking in mechanistic insight. Identifying mechanisms provides opportunities for therapies. The main impact of this study comes from using the fruit fly to identify a mechanism.

2) It is very interesting that the authors focus on an endocrine mechanism, especially with the clear clinical relevance of gut hormones to human health recently demonstrated with new, effective therapies (e.g. Wegovy).

3) Tk is emerging as an important fly hormone and this study adds a new and interesting dimension by placing TK between microbiota and lifespan.

I think the manuscript will be of great interest to researchers in ageing, human and animal physiology and in gut endocrinology and gut function.

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Referee #1

Evidence, reproducibility and clarity

Summary:

In this study the authors use a Drosophila model to demonstrate that Tachykinin (Tk) expression is regulated by the microbiota. In Drosophila conventionally reared (CR) flies are typically shorter lived than those raised without a microbiota (axenic). Here, knockdown of Tk expression is found to prevent lifespan shortening by the microbiota and the reduction of lipid stores typically seen in CR flies when compared to axenic counterparts. It does so without reducing food intake or fecundity which are often seen as necessary trade-offs for lifespan extension. Further, the strength of the interaction between Tk and the microbiota is found to be bacteria specific and is stronger in Acetobacter pomorum (Ap) monoassociated flies compared to Levilactobacillus brevis (Lb) monoassociation. The impact on lipid storage was also only apparent in Ap-flies. Building on these findings the authors show that gut specific knockdown is largely sufficient to explain these phenotypes. Knockdown of the Tk receptor, TkR99D, in neurons recapitulates the lifespan phenotype of intestinal Tk knockdown supporting a model whereby Tk from the gut signals to TkR99D expressing neurons to regulate lifespan. In addition, the authors show that FOXO may have a role in lifespan regulation by the Tk-microbiota interaction. However, they rule out a role for insulin producing cells or Akh-producing cells suggesting the microbiota-Tk interaction regulates lifespan through other, yet unidentified, mechanisms.

Major comments:

Overall, I find the key conclusions of the paper convincing. The authors present an extensive amount of experimental work, and their conclusions are well founded in the data. In particular, the impact of TkRNAi on lifespan and lipid levels, the central finding in this study, has been demonstrated multiple times in different experiments and using different genetic tools. As a result, I don't feel that additional experimental work is necessary to support the current conclusions. However, I find it hard to assess the robustness of the lifespan data from the other manipulations used (TkR99DRNAi, TkRNAi in dFoxo mutants etc.) because information on the population size and whether these experiments have been replicated is lacking. Can the authors state in the figure legends the numbers of flies used for each lifespan and whether replicates have been done? For all other data it is clear how many replicates have been done, and the methods give enough detail for all experiments to be reproduced.

Minor comments:

While I feel the conclusions of this study are well supported by the data I found this to be a complex read and in places hard to follow. I feel some work is necessary in the writing to help the reader follow the authors logic. Below I describe some of the issues that confused me and provide some suggestions that I hope the authors will find helpful.

Survival curves The authors state that the lifespan difference between CR and axenic flies disappears with TkRNAi because TkRNAi CR flies are longer lived, rather than because TkRNAi axenic flies are shorter lived. Is this consistent in every TkRNAi experiment? It's hard for the reader to assess this because the relevant lifespan curves are presented on separate plots. I'd encourage the authors to provide lifespan plots that enable comparison between all conditions. For example, in figures 2 and 6 the reader wants to directly compare between RU- and RU+ but can't easily do so. Additional plots could be made available in the supplementary figures showing the comparisons that are not easy to make on the main figures.

Consistent framing of the data Do the interventions shorten lifespan relative to the axenic cohort? Or do they prevent lifespan extension by axenic conditions? Both statements are valid, and the authors need to be consistent in which one they use to avoid confusing the reader. For example, line 325 says TkR86CRNAi prevents lifespan extension in axenic flies. Given the framing in the previous sections, it might be clearer to say that TkR86CRNAi shortens the lifespan of axenic flies to that of CR flies in contrast to TkRNAi and TkR99DRNAi which don't.

The impact of TkRNAi on lipid levels in axenic flies TkRNAi consistently reduces lipid levels in axenic flies (Figs 2E, 3D), essentially phenocopying the loss of lipid stores seen in control conventionally reared (CR) flies relative to control axenic. This suggests that the previously reported role of Tk in lipid storage - demonstrated through increased lipid levels in TkRNAi flies (Song et al (2014) Cell Rep 9(1): 40) - is dependent on the microbiota. In the absence of the microbiota TkRNAi reduces lipid levels. The lack of acknowledgement of this in the text is confusing for the reader because it is inconsistent with the microbiota driving both higher Tk expression and higher lipid storage. If the microbiota increases Tk expression and this results in reduced lipid storage, why does reduced Tk expression also result in reduced lipid storage in axenic flies? This could further highlight the unique impact that the interaction between TkRNAi and the microbiota has on lipid storage, given it reverses both the impact of the microbiota alone and TkRNAi alone. I feel this aspect of the data should be given more attention in the text both for clarity and because it may be telling us something important about the function of Tk. The current framing around pleiotropic effects is valid, and the impact of Tk on lipid storage is clearly independent of its impact on lifespan and so is not central to this study. However, I feel a short additional paragraph to acknowledge this nuance of the data is needed. It can be made clear in the text that further exploration is beyond the scope of the current study.

Role of insulin signalling and insulin producing cells I'm convinced by the data showing that FOXO is required for TkRNAi to prevent lifespan shortening by Ap, but FOXO doesn't only respond to insulin signalling and can't be taken by itself to indicate a role for insulin signalling which the authors appear to do here.

I would expect ablation of IPCs to have the opposite effect to foxo mutation and to increase FOXO activity throughout the organism due to a reduction in Dilp levels and so reduced insulin signalling. So, I have struggled to follow the authors logic in ablating the IPCs and feel a clear statement on what they expected the outcome to be would help the reader. They find that TkRNAi still prevents lifespan shortening by Ap when IPCs are ablated and that TkR99DRNAi in IPCs also doesn't block lifespan shortening by Ap despite reducing the expression of dilp3 and dilp5. To me these data rule out a role for insulin signalling despite the requirement for FOXO and yet the authors conclude that insulin signalling is involved in the response to Ap and TkRNAi, although not obligately (lines 420 - 422 and 511 - 512). Can the authors clarify their logic in concluding a role for insulin signalling, and qualify this conclusion with appropriate consideration of alternative hypotheses? The potential involvement of other signalling inputs to FOXO activity, e.g. immune signalling and JNK, should be acknowledged and warrants some discussion.

Typographical errors:

Incomplete sentence line 121 to 122 - starting "Cox proportional hazards.... and posthoc tests (Fig 2b).

Line 123 "EMMs" - define abbreviation on first use

References to Fig 2b (first given on line 122), should be capitalised to Fig 2B for consistency.

Lines 231 and 317 - the phrase "steady state (microbiota independent) expression" in reference to flyATLAS 2 data could be misleading. The term "microbiota independent" could suggest that expression levels have been shown not to be regulated by the microbiota and this is not the case. The authors should change this to simply state they are referring to steady state expression in conventionally reared flies.

Referees cross-commenting

Below are brief comments on the revision suggestions that reviewers 2 and 3 have requested.

Reviewer 2

1. I agree that confirmation that TkRNAi doesn't impact microbial levels could be helpful and would be straightforward for the authors to do. However, I don't feel it's essential to support the central claims of the paper.
2. I agree.
3. I don't feel that any of these experiments supports a role for insulin signalling, so I don't feel that this additional control is needed.
4. It would be a good addition to have lifespan data from a separate knockdown line for corroboration. However, this has already been done in several different genetic backgrounds through crosses with different driver lines in multiple tissues, so I feel it's unnecessary given the time and resources that lifespan experiments take. There's also the caveat that different RNAi lines can knockdown to different extents so that would have to be assessed as well and if there's a difference it may mean that ultimately not much can be concluded from this additional experiment.
5. A good suggestion, but not straightforward and depends on the availability of the necessary tools, or possibly the generation of new tools. One for a follow up study.
6. I feel this is not important enough to the central findings of the study to warrant the extra work.
7. I agree.

Reviewer 3 1. Imaging calcium signalling is not straightforward unless a lab already has the tools available and optimised. If Tk+ EEs show changes in calcium signalling I'm not convinced that this tells us anything specific to the Tk-microbiota interaction. The point is the role of Tk itself, not the broader activity of the cells that express it. 2. I agree this needs clarification. 3. I agree that this would add depth, if feasible, but feel it's not essential to support the current conclusions. 4. This is a minor point and given the RT-qPCR data and the RNAseq data corroborate each other I'm convinced that Tk levels are elevated. 5. I feel exploring this in males is opening an additional line of enquiry beyond the scope of the current study. Either the phenotypes are the same - in which case what is added? - or they are different but there's no scope to assess why. A good suggestion for a follow up study. 6. No comment. 7. Agreed.

One final comment. It's true that FOXO has only been shown to regulate lifespan in the context of insulin signalling. However, as far as I'm aware it hasn't been shown not to regulate lifespan downstream of it's other activators, this simply hasn't been explored due to the historical focus on insulin signalling in this field. In the context of host-microbiota interactions considering other pathways the activate FOXO, such as immune and JNK signals, would make sense.

Reviewed by Dr Rebecca Clark, Department of Biosciences, Durham University

Significance

Overall, I find the key conclusions of the paper convincing. The authors present an extensive amount of experimental work, and their conclusions are well founded in the data. We have known that the microbiota influence lifespan for some time but the mechanisms by which they do so have remained elusive. This study identifies one such mechanism and as a result opens several avenues for further research. The Tk-microbiota interaction is shown to be important for both lifespan and lipid homeostasis, although it's clear these are independent phenotypes. The fact that the outcome of the Tk-microbiota interaction depends on the bacterial species is of particular interest because it supports the idea that manipulation of the microbiota, or specific aspects of the host-microbiota interaction, may have therapeutic potential.<br /> These findings will be of interest to a broad readership spanning host-microbiota interactions and their influence on host health. They move forward the study of microbial regulation of host longevity and have relevance to our understanding of microbial regulation of host lipid homeostasis. They will also be of significant interest to those studying the mechanisms of action and physiological roles of Tachykinins.

Field of expertise: Drosophila, gut, ageing, microbiota, innate immunity

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pra ter crédito tem que contrata e paga o serviço de transporte de forma direta, não pode ser um total pago ao fornecedor com merc + frete.

mais um pra transportador pf

e a regra do crédito vinculado ao pagamernto?

limite de faturamento PF

Setor de eventos

não fala da regra do Insumo. o 52 mantém o crédito pra produto vendido aliq zero.

eLife Assessment

This work provides one of the first important attempts to look at Drosophila immune responses against bacterial, viral, and fungal pathogens in a way that combines the roles of four major arms in immunity (Imd signaling, Toll signaling, phagocytosis, and melanization) rather than studying them separately. The findings are compelling and the tools provided can be used as they are, or built upon, in various contexts.

Reviewer #1 (Public review):

Summary:

The innate immune system serves as the first line of defense against invading pathogens. Four major immune-specific modules-the Toll pathway, the Imd pathway, melanization, and phagocytosis-play critical roles in orchestrating the immune response. Traditionally, most studies have focused on the function of individual modules in isolation. However, in recent years, it has become increasingly evident that effective immune defense requires intricate interactions among these pathways.

Despite this growing recognition, the precise roles, timing, and interconnections of these immune modules remain poorly understood. Moreover, addressing these questions represents a major scientific undertaking.

Strengths:

In this manuscript, Ryckebusch et al. systematically evaluate both the individual and combined contributions of these four immune modules to host defense against a range of pathogens. Their findings significantly enhance our understanding of the layered architecture of innate immunity.

Reviewer #2 (Public review):

Summary:

In this work, the authors take a holistic view at the Drosophila immunity by selecting four major components of fly immunity often studied separately (Toll signaling, Imd signaling, phagocytosis and melanization), and studying their combinatory effects on the efficiency of the immune response. They achieve this by using fly lines mutant for one of these components, or modules, as well as for a combination of them, and testing the survival of these flies upon infection with a plethora of pathogens (bacterial, viral and fungal).

Strengths:

It is clear that this manuscript has required a large amount of hands-on work, considering the number of pathogens, mutations and timepoints tested. In my opinion, this work is a very welcome addition to the literature on fly immune responses, which obviously do not occur one type of a response at a time, but in parallel, subsequently and/or are interconnected. I find that the major strength of this work is the overall concept, which is made possible by the mutations designed to target the specific immune function of each module, without effects on other functions. I believe that the combinatory mutants will be of use for the fly community and enable further studies of interplay of these components of immune response in various settings.

To control for the effects arising from the genetic variation other than the intended mutations, the mutants have been backcrossed into a widely used, isogenized Drosophila strain called w1118. Therefore, the differences accounted for by the genotype are controlled.

I also appreciate that the authors have investigated the two possible ways of dealing with an infection: tolerance and resistance, and how the modules play into those.

Weaknesses:

While controlling for the background effects is vital, the w1118 background is problematic (an issue not limited to this manuscript) because of the wide effects of the white mutation on several phenotypes (also other than eye color/eyesight). It is a possibility that the mutation influences the functionality of the immune response components. I acknowledge that it is not reasonable to ask for data in different backgrounds better representing a "wild type" fly, but I think this matter should be brought up and discussed.

The whole study has been conducted on male flies. Immune responses show quite extensive sex-specific variation across a variety of species studied, also in the fly. But the reasons for this variation are not fully understood. Therefore, I suggest that the authors would conduct a subset of experiments on female flies to see if the findings apply to both sexes, especially the infection-specificity of the module combinations.

Comments on the revised manuscript:

I appreciate the author's responses to the points I raised and the additional work they have conducted. The authors have now discussed the possible background effect and added an experiment on female flies showing that the module function is applicable to both sexes.

Author response:

The following is the authors’ response to the original reviews.

Reviewer #1 (Public review): 

Summary: 

The innate immune system serves as the first line of defense against invading pathogens. Four major immune-specific modules - the Toll pathway, the Imd pathway, melanization, and phagocytosis- play critical roles in orchestrating the immune response. Traditionally, most studies have focused on the function of individual modules in isolation. However, in recent years, it has become increasingly evident that effective immune defense requires intricate interactions among these pathways. 

Despite this growing recognition, the precise roles, timing, and interconnections of these immune modules remain poorly understood. Moreover, addressing these questions represents a major scientific undertaking. 

Strengths: 

In this manuscript, Ryckebusch et al. systematically evaluate both the individual and combined contributions of these four immune modules to host defense against a range of pathogens. Their findings significantly enhance our understanding of the layered architecture of innate immunity. 

We thank the reviewer for their kind assessment.

Weaknesses: 

While I have no critical concerns regarding the study, I do have several suggestions to offer that may help further strengthen the manuscript. These include: 

(1) Have the authors validated the efficiency of the mutants used in this study? It would be helpful to include supporting data or references confirming that the mutations effectively disrupted the intended immune pathways. 

We have done so in Figure 1.

(2) Given the extensive use of double, triple, and quadruple mutants, a more detailed description of the mutant construction process is warranted. 

We now provide a supplement (File S1) that details the successive genetic crosses and recombinations that were required to generate these compound fly stocks carrying multiple mutations. We also provide some information regarding rapid screening of stocks for phenotypes. Of note some of these fly stocks have been deposited at VDRC as they will be useful to fly community to assess immune modules in a controlled background, and complete stock information will be tied to these stocks there.

Reviewer #2 (Public review): 

Summary: 

In this work, the authors take a holistic view of Drosophila immunity by selecting four major components of fly immunity often studied separately (Toll signaling, Imd signaling, phagocytosis, and melanization), and studying their combinatory effects on the efficiency of the immune response. They achieve this by using fly lines mutant for one of these components, or modules, as well as for a combination of them, and testing the survival of these flies upon infection with a plethora of pathogens (bacterial, viral, and fungal). 

Strengths: 

It is clear that this manuscript has required a large amount of hands-on work, considering the number of pathogens, mutations, and timepoints tested. In my opinion, this work is a very welcome addition to the literature on fly immune responses, which obviously do not occur in one type of response at a time, but in parallel, subsequently, and/or are interconnected. I find that the major strength of this work is the overall concept, which is made possible by the mutations designed to target the specific immune function of each module (at least seemingly) without major effects on other functions. I believe that the combinatory mutants will be of use for the fly community and enable further studies of the interplay of these components of immune response in various settings. 

To control for the effects arising from the genetic variation other than the intended mutations, the mutants have been backcrossed into a widely used, isogenized Drosophila strain called w1118. Therefore, the differences accounted for by the genotype are controlled. 

I also appreciate that the authors have investigated the two possible ways of dealing with an infection: tolerance and resistance, and how the modules play into those. 

We thank the reviewer for their kind assessment. 

Weaknesses: 

While controlling for the background effects is vital, the w1118 background is problematic (an issue not limited to this manuscript) because of the wide effects of the white mutation on several phenotypes (also other than eye color/eyesight). It is a possibility that the mutation influences the functionality of the immune response components, for example, via effects of the faulty tryptophan handling on the metabolism of the animal. 

I acknowledge that it is not reasonable to ask for data in different backgrounds better representing a "wild type" fly (however, that is defined is another question), but I think this matter should be brought up and discussed. 

We agree with the reviewer and have included caveats on the different genetic effects brought about the combinatory mutant approach including differences in white gene status, insertion of GFP or DsRed markers, and nature of genetic mutations (Line 142-on).

“Of note, the strains used in this study differ in their presence/absence of the white⁺ gene, present in the PPO1^∆, NimC1¹ and eater¹ mutations.  In addition to its well established function in eye pigmentation, the white gene can also impact host neurology and intestinal stem cell proliferation (Ferreiro et al., 2017; Sasaki et al., 2021). We did not observe any obvious correlations between white⁺ gene status and susceptibilities in this study. Moreover,  in a previous study looking at the cumulative effects of AMP mutations on lifespan, white gene status and fluorescent markers did not readily explain differences in longevity (Hanson and Lemaitre, 2023). We therefore believe that the extreme immune susceptibility we have created through deficiencies for pathways regulating hundreds of genes, or major immune modules, overwhelms the potential effects of white⁺ and other transgenic markers. For additional information on which stocks bear which markers, see discussion in Supplementary file 1.”

Of interest, we were highly conscious of this concern in working with combinatory AMP mutants which differed in white, GFP, and DsRed copies. However, even over the many weeks of snowballing effects on microbiota community composition and structure, we found no trends tied strictly to white+ or to other genetic insertions on lifespan (Hanson and Lemaitre, 2023; DMM).

The whole study has been conducted on male flies. Immune responses show quite extensive sex-specific variation across a variety of species studied, also in the fly. But the reasons for this variation are not fully understood. Therefore, I suggest that the authors conduct a subset of experiments on female flies to see if the findings apply to both sexes, especially the infection-specificity of the module combinations.  

We thank the reviewer for this suggestion. We have performed the requested experiments, and include female survival trends in Figure 4supp1. We have added the following text to the main manuscript (Line 554):

“All survival experiments to this point were done with males. We therefore assessed key survival trends for these infections in females to learn whether the dynamics we observed were consistent across sexes (Figure 4supp1). For all three pathogens (Pr rettgeri, Sa aureus, C. albicans) the rank order of susceptibility was broadly similar between males and females, with higher rates of mortality in females overall. Thus, we found no marked sex-bygenotype interaction. Interestingly, the greater susceptibility of females in our hands is true even for ∆ITPM flies, although there are only a few surviving flies on which we can base these conclusions. However, these data may suggest the sexual dimorphism in defense against infection that we see against these pathogens is due to factors independent of the immune modules we disrupted.”

It is worth noting that male-female sex dichotomies in infection are inconsistent across the literature, with strong lab-specific effects (Belmonte et al., 2020 and personal observation). In our lab setting, we consistently see female mortality higher than males when compared, independent of pathogen and mutant background. We have not seen notable interaction terms of sex and genotype for most immune deficient mutants. It is quite interesting to have done these experiments with ITPM, however, which reveals that there is at least a trend suggesting this dichotomy is independent of the four immune modules we deleted. Still, our infection conditions kill most males, and so it would be good to replicate this sex-specific ∆ITPM result in a dedicated study with doses chosen to improve the resolution of male-female differences. For now, we prefer to use conservative language and avoid overinterpreting this trend, but do feel it merits mentioning.  

Recommendations for the authors:

Comment on statistical requests

Both reviewers requested further clarity on the statistical analyses supplemental to Figure 3. We haved address these comments as follows.

First, we now provide an additional supplementary .zip file containing summary statistics for all survival data in Figure 3 (Supplementary File 3). We have additionally added this text to line 226 to make this data treatment more clear:

…” we chose to focus on major differences apparent in summary statistics,Highlighting”…

And we highlight that all survival data are also provided as Kaplan-Meier survival curves in the main or supplementary figures in Line 233:

“Kaplan-Meier survival curves for all experiments are provided in the main text or supplementary information”.

Second, as outlined in the main text, we were unable to sample across all pathogenby-genotype interactions systematically, and this unfortunately obfuscates robust statistical modelling. We addressed the challenge of finding meaningful statistical differences by focusing on trends only if they were i) consistent across experimental replicates, ii) of a consistent logic across comparable genotypes, ensuring random inter-experimental noise was not unduly shaping interpretations, and iii) of a mean lifespan difference ≥1.0 days compared to wild-type, and compared to relevant unchallenged or clean-injury controls. This last choice was especially important because not all experimental replicates included all genotypes due to challenges of animal husbandry and coordination among multiple researchers over five years of data collection. As a result, our initial analyses using a cox mixed-effects model found it to be rather useless, being insensitive to important experiment batch effects visible to the eye because statistically-affected genotypes were not present in all experiments.

We therefore ensured that behaviour relative to controls within* experiments was consistent, rather than the comparison of genotypes to controls across the sum of experiments with a post-hoc treatment attempting to apportion variance to experiment batch (but unable to do so for some genotypes and some batches). Due to differeces in baseline health and the dynamics explained by studies like Duneau et al. (2017; eLife, there is an expected unequal variance of genotype*pathogen interactions across experiment batches. Unfortunately, this unequal variance, coupled with incomplete sampling across experiment batches, means “highly significant” differences can emerge that don’t hold up to scrutiny of comparisons to controls taken only from within an experiment batch. Thus, we chose to forego a cox mixed effect model approach entirely. Instead, our highly conservative approach, focusing on only very large effects with a mean lifespan difference ≥1.0 days, mitigates these issues. We have taken great care to ensure that any results we highlight stand up to inter-experiment batch effects. We would further draw the reviewers’ attention to our response to Reviewer 2 relating to Figure 3, which emphasizes the level of conservativism that we are applying.

At the end of the Discussion, we have added the following sentence to emphasize these limitations:

“…a combinatorial mutation approach to deciphering immune function can be extended even to the broad level of whole immune modules. Of note, we were unable to systematically sample all genotype-bypathogen interactions equally. We have therefore been highly conservative in our reporting of major effects. There are likely many important interactions” not discussed in our study. Future investigations may highlight important biology that is apparent in our data, but which we may not have mentioned here. To this end, we have deposited our isogenic immunity fly stocks in the Vienna Drosophila Resource Centre to facilitate their use. Beyond immunity, our tools can also be of use to study various questions at the cutting edge of aging, memory, neurodegeneration, cancer, and more, where immune genes are repeatedly implicated. We hope that this set of lines will be useful to the community to better characterize the Drosophila host defense.”

We recognise this response may not fully satisfy the reviewers’ requests. While use of summary statistics is simple, our rules for highlighting interactions of importance are defined, readily understood and interpreted, and draw attention to key trends in that are backed by a solid understanding of the data and its limitations. We have taken this approach out of a responsibility to avoid making spurious assertions that stem from underpowered statistical models rather than from the biology itself.

Reviewer #1 (Recommendations for the authors): 

(1) Lines 1092-1093 - Please double-check the labeling of the panels in Figure 2. It appears that panels A and C correspond to single-module mutants, whereas panels B and D refer to compound-module mutants. 

We have modified Figure 2 and Figure 2supp1 labelling. We also realise there was an error in the column titling that contributed to the confusion. We hope the new layout is clear, and thank the reviewers for noting this issue.

(2) Lines 347-377 - Figure 2D is not cited in the text. 

We now cite Fig2D in Line 356.

(3) P values should be indicated in Figure 2 and Figure 3 for all relevant comparisons. Additionally, "ns" (not significant) should be added in Figure 5A-B. 

We make the effort to show key uninfected survival trends in Figure 2, and list the total flies (n_flies) in Fig3 to provide the reader with the underlying confidence in the trends observed. We focus on differences of mean lifespan of at least 1 day, and which are consistent in direction across combinatory mutations.  We have avoided the multiple comparisons of cox proportional hazard survival analyses throughout this study because they are overly sensitive for our purposes, as we have previously when systematically comparing many genotypes to each other (see Hanson and Lemaitre, 2023; DMM).

(4) Minor points: Hml-Gal4, UAS-GFP should be italic; Line 192-- "uL" and "uM"; Line 596: P>.05.

We have made these changes. We’re unsure what the comment regarding P>.05 referred to, but have removed spaces and made it non-italics. 

Reviewer #2 (Recommendations for the authors): 

Statistical analyses and their outcomes are clearly indicated only for the data in Figure 1 and Figure 5 and in the supplement for Figure 1, while they are not reported/not easily accessible for other data. For the main figures, statistics should be indicated in the figure for an easier assessment of the data. In case of multiple comparisons potentially crowding the plots too much, statistics may be in a supplementary file/table. 

See response above.

In case of the hemocytes, besides phagocytosis, I would think that ROS generation via the DUOX/NOX system is also an integral part of the immune response against pathogens, and that has not been included here. That might be an interesting addition for future experiments. As the NimC1, eater double mutant flies are said to have fewer hemocytes, it is possible that this function of the hemocytes is affected as well. This could be commented on in the text. 

The reviewer raises a good point. The role of DUOX and NOX in ROS responses is not assessed in our study. To our knowledge, DUOX and NOX participate primarily in the wound repair response, or in epithelial renewal at damage sites or in the gut. In our study on systemic immunity, we did not assess the role of clotting, the precise function of ROS, and we have missed other host defense or stress response mechanisms as well (e.g. constitutively-expressed AMP-like genes, TEPs, JAK-STAT) that likely play a role in the systemic immune defense. Considering the lethality caused by Nox and Duox mutation, there would be inherent genetic difficulties to recombine these as multiple mutations. Unfortunately, this makes it  difficult to include these processes in our analysis in a systematic manner.  We are already happy to have generated fly lines lacking four immune modules simultaneously, even if they are not fully immune deficient. We have mentioned this point in the discussion (Line 613-on).

Of note, the NimC1, eater double mutants actually have decreased hemocyte counts at the adult stage (Melcarne et al,. 2019). Thus NimC1, eater double mutants are not impaired only in phagocytosis, but the overall cellular response. We make a point to outline this in Line 225-257, and 607.

I think it could be mentioned that the melanization response at larval stage (against parasitoids) functions differently from the melanization described here (requiring hemocyte differentiation and PPO3).

A good point. We have added this mention in Line 97:

“In addition, a third PPO gene (PPO3) is specifically expressed by lamellocytes, specialized hemocytes that differentiate in larvae responding to and enveloping invading parasites (Dudzic et al., 2015)”.

Overall, the clarity of the figures and figure legends could be worked on to make them a bit easier to follow. Below are some of my suggestions: 

(1) In Figure 2, adding headings to parts C & D (similarly to A & B) would make it easier to follow what is happening in the figure at a glance. Also, it is rather difficult to visually follow which strain is which in the plots. I'd suggest adding the key/legend for single mutants below 2A & B, and the key for the double mutants below C & D. If a mutant is present in A & B and in C & D, it could be included in both keys. I also think that it would be intuitive to present the single mutants by dashed lines and double mutants by continuous lines (or vice versa), so that one would easily distinguish between them. Of note, the figure legend says that A & B are single mutants, but for example in B there are also some double mutants (?). 

We have modified Figure 2 and Figure 2supp1 labelling. We also realise there was an error in the column titling that contributed to the confusion. We hope the new layout is clear, and thank the reviewers for noting this issue.

(2) In Figure 3, it looks like ΔMel is almost identical to controls in the clean injury survival, but in Figure 2C, it is clearly doing worse. I might be missing something here, but would like the authors to clarify the matter. Also, the meaning of the numbers in the heat map could be explained in the figure legend and/or added to the figure (color key). 

The reviewer is correct. We thank the reviewer for this astute observation. Inadvertently, we used an old version of the Figure 2 preparation where only a subset of experiments was entered in the Prism data file rather than the total data used to inform Figure 3. This issue affected all genotypes.

We have reviewed the data in Figure 2, Figure 2supp1, and Figure 3, and updated these figures accordingly to ensure they represent the full survival data. We have also incorporated new experiments into the sum data related to male-female differences and to fill gaps in the data from the 1^st submission. We will also note due to the nature of 1^st decimal rounding that the difference between WT and ΔMel appears slightly underrepresented: the true difference (over the 7-day lifespan) is 0.37. We’ve provided a version of this figure rounded to 2 decimal places below, but prefer the simpler 1 decimal place in the main text for readability. The updated Figure 2 shows the full data in Figure 3 accurately.

We will also take this opportunity to highlight how conservative our ≥1.0 days difference approach is. Breaking down survival curve patterns in Figure 2 relative to mean differences in Figure 3, for clean injury, approximately ~75% of ΔMel flies survive to day 7 with mortality mostly taking place between days 3-7. The result is a mean lifespan of 6.37 days. On a survival curve, this difference appears quite strong, but in our mean lifespan table the difference is rather muted (WT vs. ΔMel difference = 0.37 days). Thus, differences of ≥1.0 days reflect very strong trends in survival data that are near-guaranteed to be independent of experimental noise. While we note issues that prevented us from a fully systematic sampling for all experiments, we are confident that the ≥1.0 day differences we highlight, using the rules explained in the main text, are robust. While this approach could be seen as overly conservative, it is our preference in this initial study, containing combinations of 25 treatments and 14 genotypes, to be highly conservative. Future studies may investigate other strong differences we have not highlighted, and the data we provide here can help generate expectations and guide those studies.

Author response image 1.

Figure 3 with 2 decimals places of rounding for mean lifespans. The 7-day clean injury mean lifespan of WT is 6.74 days, and of ΔMel is 6.37 days. Due to rounding, in the 1 decimal Figure 3 this difference appears as if it is only 0.3 days, but it closer to 0.4 days. Regardless, this level of difference, which appears rather clearly in a survival curve, is well below the level of difference we have chosen to highlight in our study.

(1) Figure 4: I find it very tedious to compare CFUs among different mutants from the plots. As the idea is to compare bacterial loads among the mutants at different timepoints, it would be easier to compare them if the data were shown within a timepoint (CFUs of each mutant at 2h, at 6h, and so on). This is also how the results are written in the text (within a time point). Would it also be clearer if the CFU plots were named, for example: " A', B', and C'"? 

We appreciate this note. We feel both representations have merits and pitfalls, but prefer our original design showing the progression of bacterial growth within genotype first. However, we have added dotted lines representing the wild-type bacterial loads at 2hpi, 12hpi, and 24hpi to assist the reader in making acrossgenotype comparisons at key time points. Like this, the reader can see if the error bars (StDev) overlap the mean of the wild-type, and so make more intuitive judgements about whether these differences are meaningful.

(2) Figure 2D is not referred to in the text. 

We now cite Fig2D in Line 356.

hes not filthy :(

I'm somehow missing the transition from general networks to the networks of charging stations. Should we consider the charging station networks on this level at all, or better to handle it as an use case example?

Is the meaning "gateway shows" or "the section "Mobile radio gateway" shows"?

A long dash would be better. Or at least it have to be used consistently within the document.

Long dash looks strange here: shouldn't it be wrapped by spaces?

space between number and unit

Is there a better wording?

Incomplete sentence

Spaces before "m" unit.

Should here be a period at the end of each point? It should be at least consistent.

space between number and unit

Is it not better to use standard SI unit notation like "5 s" instead of "5 sec."? It looks somehow strange, at least for me.

taxnegative = distortionary taxes and unproductive spending, or nondistortionary taxes, lowers growth -0.18

taxambigous = lower -0.11

taxpositive = 0.02 growtyh

taxpositive = positive economic growth. taxnegative = negative growth. this is the theory on what forms of taxation create this

publication bias

findings

findings

math

growth tax effect

past methods

big idea

gun up unemploymet dgaf. gun up investment down

gun up investment down

gun up gdp down a little bit

military dont afect unemploument

nongun up unemployment down

nongun up productive up

guns up private investment down

contemporarous equation math

holy shit thats math

data

opportunity cost

guns gdp

guns employ math

guns employ but take job

guns employ

guns butter math

guns butter

defense-growth chart

supply side

demand side

Unexpected explanation for PLC. Expected: Power Line Communication, probably with more description.

Document d'information : La Santé Mentale des Mineurs en France

video Présentation du rapport à l'Assemblée nationale

Résumé

Ce document synthétise les conclusions du rapport d'information de l'Assemblée Nationale sur la santé mentale des mineurs.

Le constat principal est un écart grandissant et critique entre une demande de soins en forte augmentation et une offre de soins publique saturée, sous-financée et géographiquement inégale.

Cette crise systémique entraîne des prises en charge tardives, un recours accru aux psychotropes et une saturation des services d'urgence.

La hausse de la demande est un phénomène multifactoriel, résultant d'une meilleure détection des troubles et d'une moindre stigmatisation, mais aussi de l'impact croissant de déterminants sociaux, environnementaux et numériques.

Les violences intrafamiliales, la précarité, la pression scolaire (notamment via Parcoursup), l'exposition aux écrans et un contexte général anxiogène (géopolitique, environnemental) sont identifiés comme des facteurs majeurs.

Les populations les plus vulnérables, notamment les enfants suivis par l'Aide Sociale à l'Enfance (ASE) et les mineurs non accompagnés (MNA), sont particulièrement touchées et leur prise en charge est souvent défaillante.

Face à cette situation, le rapport préconise une double stratégie ambitieuse.

D'une part, il appelle à une consolidation de l'offre de soins existante, en réaffirmant les principes fondateurs de la psychiatrie de secteur.

Cela implique de renforcer le maillage territorial, de rendre effective une gradation des soins (médecins généralistes, Maisons des Adolescents en première ligne ; Centres Médico-Psychologiques comme pivot ; centres de crise pour les urgences) et d'améliorer la coordination entre les secteurs sanitaire, social et éducatif.

D'autre part, le rapport insiste sur la nécessité de déployer des politiques de prévention robustes, en agissant sur trois environnements clés :

1. L'environnement familial : via un soutien renforcé à la parentalité, notamment durant la période périnatale (les 1000 premiers jours).

2. L'environnement scolaire : en restaurant la capacité de détection précoce des services de santé scolaire et en apaisant un climat jugé trop compétitif et anxiogène.

3. L'environnement numérique : par une régulation de l'usage des écrans et des campagnes de prévention sur les dangers de l'addiction.

La mise en œuvre de ces recommandations nécessite un investissement financier pérenne, une revalorisation des professions de la pédopsychiatrie pour renforcer leur attractivité, et une meilleure formation de l'ensemble des professionnels au contact des enfants.

Perspectives des Rapporteures

Les deux co-rapporteures, bien que partageant de nombreuses préconisations, soulignent des priorités et des analyses distinctes dans leurs avant-propos.

Mme Nathalie Colin-Oesterlé met l'accent sur :

• La prévention comme axe clé, en particulier durant la période de la conception aux deux ans de l'enfant.

• Le rôle décisif des parents, insistant sur les conséquences de leur absence psychique ou physique et le manque de cadre.

• Les dangers de l'addiction aux écrans, soutenant la majorité numérique et une "pause numérique" dans les établissements scolaires.

• La nécessité d'une meilleure gradation des soins et d'une coopération renforcée entre les secteurs public et privé pour désengorger les Centres Médico-Psychologiques (CMP).

Mme Anne Stambach-Terrenoir insiste sur :

• Le manque structurel de moyens de la pédopsychiatrie publique, critiquant une "réponse néolibérale" qui privilégie la réorganisation à l'investissement.

• Les déterminants sociaux des troubles mentaux, liant la dégradation de la santé mentale à l'augmentation des inégalités sociales, à la précarité et aux évolutions du monde du travail (horaires atypiques).

• Les effets anxiogènes du système scolaire, citant Parcoursup et les réformes Blanquer comme des facteurs aggravants.

• L'urgence de redonner des moyens financiers et humains aux services publics existants (santé, Éducation nationale, ASE) plutôt que de financer des "projets innovants" non pérennes.

I. Un Écart Croissant entre la Demande et l'Offre de Soins

Le rapport dresse le constat d'une crise profonde, caractérisée par une demande de soins psychiques exponentielle face à une offre contrainte, fragmentée et souvent inaccessible.

A. Un Enjeu de Santé Publique Majeur

1. Augmentation et Nature de la Demande de Soins

• Prévalence : Selon la DGOS, 1,6 million d'enfants et d'adolescents en France souffriraient d'un trouble psychique.

• Données Épidémiologiques :

◦ L'enquête Enabee (2022) révèle que 13 % des enfants de 6 à 11 ans et 8,3 % des 3-6 ans présentent un trouble probable de santé mentale.   

◦ L'enquête Enclass (2022) sur les collégiens et lycéens montre que 14 % des collégiens et 15 % des lycéens présentent un risque important de dépression. 24 % des lycéens déclarent des pensées suicidaires au cours des 12 derniers mois.

• Différences de Genre : Les enquêtes confirment une prévalence plus forte des troubles internalisés (anxio-dépressifs) chez les filles, et des troubles externalisés (comportement, hyperactivité) chez les garçons.

• Interprétation des Données : Plusieurs experts auditionnés appellent à la prudence, soulignant que la notion de "trouble probable" ne constitue pas un diagnostic clinique et qu'il existe un risque de médicalisation excessive de phénomènes développementaux normaux ou de difficultés sociales.

• Une Parole Libérée : L'augmentation des demandes s'explique aussi par une meilleure connaissance des troubles, une déstigmatisation progressive et une plus grande capacité des jeunes et de leurs parents à exprimer une souffrance psychique.

2. Un Phénomène Multifactoriel

La dégradation de la santé mentale des mineurs est le produit de multiples facteurs :

• Violences : 30 % des patients en pédopsychiatrie sont victimes de maltraitance parentale. L'exposition aux violences (physiques, sexuelles, psychologiques, intrafamiliales) est un déterminant majeur.

• Déterminants Sociaux : La précarité, les conditions de logement et le niveau de revenu sont corrélés à un risque plus élevé de développer des troubles mentaux.

• Environnement Numérique : L'exposition excessive aux écrans est unanimement identifiée comme un facteur aggravant les troubles anxieux dépressifs. Elle perturbe le sommeil, isole et expose à des contenus préjudiciables (cyberharcèlement, contenus violents, pornographiques).

• Environnement Social Anxiogène :

◦ Milieu scolaire : Le harcèlement (5% des élèves du CE2 au CM2, 6% des collégiens), la pression liée à la performance, l'inadaptation de certains programmes et un système d'orientation jugé anxiogène (Parcoursup) contribuent au stress et au "refus scolaire anxieux".  

◦ Contexte global : L'éco-anxiété et les peurs liées au contexte géopolitique (guerres, attentats) participent également à l'angoisse des jeunes.

3. Prise en Charge Défaillante des Populations les plus Vulnérables

• Aide Sociale à l'Enfance (ASE) : Les enfants suivis par l'ASE sont surreprésentés dans les services de psychiatrie (occupant jusqu'à 40-50 % des lits d'hospitalisation à temps plein). Leurs parcours chaotiques et les carences affectives engendrent des troubles sévères, mais leur suivi médical est souvent défaillant et discontinu.

L'hôpital se substitue parfois à un lieu d'hébergement.

• Mineurs Non Accompagnés (MNA) : Ces jeunes souffrent massivement de stress post-traumatique lié à des parcours migratoires extrêmement violents (guerres, torture, naufrages).

Leurs conditions d'accueil et les procédures d'évaluation de leur minorité aggravent leur vulnérabilité et complexifient leur accès aux soins.

B. Une Offre de Soins Insuffisante et Illisible

Le système de la "sectorisation", conçu pour garantir un accès équitable aux soins, est aujourd'hui saturé.

1. Une Offre Contrainte face à une Demande Croissante

• Moyens Inadaptés : 58 % des lits d'hospitalisation en pédopsychiatrie ont été supprimés entre 1986 et 2013. De nombreux jeunes sont hospitalisés en services pour adultes, avec les risques que cela comporte.

• Pénurie de Soignants : La situation est critique, notamment pour les pédopsychiatres, dont le nombre a diminué de 34 % entre 2010 et 2022.

La profession est vieillissante (moyenne d'âge de 60 ans) et peu attractive pour les jeunes médecins.

La pénurie concerne également les infirmiers, les médecins scolaires et les psychologues dans le secteur public.

• Disparités Territoriales : L'accès aux soins est très inégal. La densité de pédopsychiatres varie fortement d'une région à l'autre (ex: 9 pour 100 000 jeunes en PACA, 3 en Hauts-de-France).

Les zones rurales et les départements d'outre-mer sont particulièrement sous-dotés.

2. Une Multiplicité d'Acteurs Rend l'Offre Illisible

Bien que des structures comme les Maisons des Adolescents (MDA) et les Équipes Mobiles (EMPEA) jouent un rôle crucial, la multiplication des dispositifs et des centres experts (qui posent des diagnostics sans assurer de suivi) rend le parcours de soins complexe et illisible pour les familles.

3. Des Conséquences Déléteres

• Prise en Charge Tardive : Les délais d'attente pour un premier rendez-vous en Centre Médico-Psychologique (CMP), pivot du système, peuvent atteindre 12 à 18 mois, conduisant à une aggravation des troubles.

• Recours Accru aux Psychotropes : Face à la saturation des dispositifs de suivi thérapeutique, la prescription de psychotropes aux mineurs a augmenté de 18 % entre 2019 et 2023.

Cette médicalisation est souvent perçue comme une solution par défaut.

• Saturation des Urgences : Faute de prise en charge en amont, les services d'urgence deviennent le lieu du premier diagnostic lors de crises aiguës, ce qui contribue à leur engorgement.

II. Stratégies de Consolidation de l'Offre et de Prévention

Le rapport formule 53 recommandations visant à la fois à renforcer le système de soins existant et à mettre en œuvre une politique de prévention ambitieuse.

A. Améliorer la Prise en Charge

1. Rendre l'Offre de Soins Graduée et Effective

• Réaffirmer le Rôle du Secteur : La priorité est de consolider le maillage existant plutôt que de créer de nouveaux dispositifs. Le CMP doit rester le pivot du parcours, avec un accueil inconditionnel.

• Mettre en Place une Gradation Claire :

◦ Premier niveau : Médecins généralistes, pédiatres, psychologues de ville et Maisons des Adolescents (MDA), qui doivent être adossées à des centres de soins.  

◦ Deuxième niveau : Les CMP, dont les moyens et le maillage doivent être renforcés (objectif : un accès en moins de 30 minutes pour chaque enfant).   

◦ Gestion des crises : Création de centres de crise adossés aux urgences pédiatriques pour les épisodes aigus, limitant ainsi le recours aux urgences générales.

2. Renforcer la Formation et l'Attractivité des Professions

• Formation : Il est crucial de mieux former tous les professionnels : médecins généralistes (détection précoce), infirmiers (stage obligatoire en psychiatrie, développement de la pratique avancée), professionnels de la petite enfance (théorie de l'attachement).

• Attractivité : Pour lutter contre la pénurie, il est préconisé de revaloriser les salaires et les tarifs des consultations, d'améliorer les conditions de travail et de créer une chaire de psychiatrie de l'enfant et de l'adolescent dans chaque CHU pour revaloriser la discipline.

3. Améliorer la Coordination et le Financement

• Coordination Intersectorielle : Une meilleure articulation est nécessaire avec l'ASE (création de structures mixtes soin-hébergement), l'Éducation nationale (redynamisation des RASED, intégration de la santé scolaire dans les projets de santé mentale) et le secteur médico-social (adossement des CMPP au secteur sanitaire).

• Financement : Le rapport appelle à pérenniser et flécher les budgets de la pédopsychiatrie, à privilégier les dotations pluriannuelles aux appels à projets, et à réformer le codage des actes pour valoriser le temps de coordination et d'échange avec les familles, qui est au cœur du soin pédopsychiatrique.

B. Privilégier les Politiques Préventives

1. Agir sur l'Environnement Familial

• Périnatalité et 1000 Premiers Jours : C'est une période cruciale. Il faut développer les équipes dédiées à la périnatalité dans chaque CMP, étoffer les unités d'hospitalisation conjointes parents-bébé et généraliser les "maisons des 1000 premiers jours" pour accompagner tous les parents.

• Soutien à la Parentalité : Les parents sont des acteurs essentiels de la prise en charge.

Il faut renforcer les dispositifs qui les accompagnent et les forment, notamment via des associations et des groupes de parole.

2. Agir sur l'Environnement Scolaire

• Renforcer la Santé Scolaire : Il est urgent d'engager un plan de recrutement massif de médecins scolaires, d'infirmiers et de psychologues de l'Éducation nationale pour atteindre des ratios acceptables.

• Rendre la Détection Précoce Effective : Les bilans de santé à 6 ans et 12 ans doivent être systématiquement réalisés et inclure un volet de dépistage des troubles de santé mentale.

• Apaiser le Climat Scolaire : L'école doit devenir un lieu moins anxiogène, en favorisant les compétences psychosociales (cours d'empathie) et en réformant un système d'orientation jugé trop précoce et compétitif.

3. Agir sur l'Environnement Numérique

• Responsabiliser les Parents : Il est essentiel de sensibiliser les parents à leur propre usage des écrans et à l'"absence psychique" qui en découle, ainsi qu'à la nécessité de passer du temps qualitatif sans écrans avec leurs enfants.

• Déployer des Campagnes de Prévention : Des campagnes massives sur les dangers de l'addiction aux écrans sont nécessaires.

• Réguler à l'École : La "pause numérique" (interdiction des téléphones portables) doit être généralisée dans tous les établissements scolaires.

La majorité numérique doit également être rendue effective pour protéger les plus jeunes.

Taney points to old state laws that treated Black people unfairly and says this proves they were never meant to be citizens. He’s using discrimination as evidence. I disagree because laws that were unjust shouldn’t be used to defend injustice. They show racism, not truth.

Taney claims that since enslaved Africans weren’t considered “the people” back then, they can’t be citizens now. He’s using historical exclusion as proof. I strongly disagree because “all men are created equal” should apply to everyone. Just because people were wrong in the past doesn’t mean we should keep those ideas alive.

Taney looks back to colonial times to decide who counts as a citizen. He uses old laws and traditions to prove his point, which is exactly how originalists think. I disagree because those old systems supported slavery. Using them as a guide for freedom is unfair and outdated.

Here, Taney says judges have to follow what the Constitution meant when it was first written. He doesn’t believe it should change with time or new ideas. I disagree because that way of thinking keeps the country stuck in the past. The Constitution should grow with society and reflect fairness for everyone.

Taney is asking if Black people can ever be part of the “political community” that the founders created. He basically says that since the people who wrote the Constitution didn’t see them as citizens, they still aren’t. I disagree because Taney uses racist beliefs from the 1700s to decide what’s right now. The founders’ views shouldn’t stop people from being treated equally today.

model context protocol (mcp)

Contextualisme in het recht is de gedachte dat je het recht, een wet of een juridische zaak alleen goed kunt begrijpen door rekening te houden met de omstandigheden waarin de wet is gemaakt (de historische context) en de specifieke situatie waarin het recht wordt toegepast (de concrete context). Het gaat erom de betekenis van een regel te zien binnen de bredere context van het geval, omdat regels niet altijd een eenduidige, letterlijke betekenis hebben, maar eerder afhangen van de omstandigheden.

aanvullend

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What does this mean?

Yes, they can - gradually, iteratively

If the institutions are effective - is there enough motivation to create informal mechanisms for addressing "gaps"? If actors are mindful of the sanctions for transgressions - aren't informal institutions also not those transgressors?

It's not only about the result - it's about what gets knocked over and broken in the process of reaching the result

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study later

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Great one

3. É possível indeferir pedido de desistência recursal, veiculado anteriormente ao julgamento, desde que a negativa de desistência seja avaliada pelo colegiado em questão de ordem, levando-se em consideração:

• (i) se tratar de tema nunca enfrentado no STJ ("leading case"),

• (ii) haver indícios de estratagema a evitar jurisprudência em pedidos de desistência homologados anteriormente envolvendo o mesmo desistente,

• (iii) o sorteio de relatoria preceder a apresentação do pedido de desistência e

• (iv) haver forte interesse público no enfrentamento do objeto recursal a recomendar orientação jurisprudencial nacional.

(REsp n. 2.172.296/RJ, relatora Ministra Nancy Andrighi, Terceira Turma, julgado em 4/2/2025, DJEN de 7/2/2025.)

A execução provisória de astreintes é possível. No entanto, o levantamento do valor está condicionado ao trânsito em julgado da sentença favorável ao exequente.

• Informativo nº 844
• 25 de março de 2025.
• RECURSOS REPETITIVOS
• Processo: REsp 2.021.665-MS, Rel. Ministro Moura Ribeiro, Corte Especial, por maioria, julgado em 13/3/2025. (Tema 1198).

Ramo do Direito DIREITO CIVIL, DIREITO PROCESSUAL CIVIL

TemaPaz, Justiça e Instituições Eficazes <br /> Demandas abusivas. Documentos capazes de comprovar a seriedade da demanda. Exigência. Finalidade. Coibição de fraude processual. Tema 1198.

Destaque - Constatados indícios de litigância abusiva, o juiz pode exigir, de modo fundamentado e com observância à razoabilidade do caso concreto, a emenda da petição inicial a fim de demonstrar o interesse de agir e a autenticidade da postulação, respeitadas as regras de distribuição do ônus da prova.

Informações do Inteiro Teor - Cinge-se a controvérsia em verificar a possibilidade de o juiz, em um estágio inicial do processo, exigir que a parte apresente documentos capazes de evidenciar a verossimilhança do direito alegado, pavimentando, dessa forma, o caminho para a entrega de uma tutela jurisdicional efetiva e coibindo, a um só tempo, a prática de fraudes processuais. Ou seja, saber até que ponto ou em qual medida o juiz, antevendo a natureza temerária da lide, pode exigir da parte autora que apresente documentos capazes de confirmar a seriedade da pretensão deduzida em juízo.

• Nas sociedades de massa, em que a grande maioria da população integra processos de produção, distribuição e consumo de larga escala, é esperado o surgimento de demandas e lides também massificadas. Essa litigância de massa, conquanto apresente novos desafios ao Poder Judiciário, constitui manifestação legítima do direito de ação.

• Observa-se, no entanto, em várias regiões do país, verdadeira avalanche de processos infundados, marcados pelo exercício de advocacia abusiva, predatória, que não encontra respaldo no legítimo direito de ação. Tais feitos não apenas embaraçam o exercício de uma jurisdição efetiva, mas verdadeiramente criam sérios problemas de política pública, conforme identificado por órgãos de inteligência de vários tribunais do país.

• A possibilidade de o juiz exigir a apresentação de documentos para comprovar o interesse de agir ou a verossimilhança do direito alegado tem sido admitida por esta Corte e também pelo Supremo Tribunal Federal (STF) em diversas situações.

• Por isso, poderá o juiz, a fim de coibir o uso fraudulento do processo, exigir que o autor apresente extratos bancários, cópias de contratos, comprovante de residência, procuração atualizada e com poderes específicos, dentre outros documentos, a depender de cada caso concreto.

• A procuração outorgada para determinada causa em regra não subsiste para outras ações distintas e desvinculadas, porque uma vez executado o negócio cessa o mandato para o qual outorgado (art. 682, IV, do Código Civil - CC). Assim, caso o advogado apresente instrumento muito antigo, dando margem a descrença de que não existe mais relação atual com o cliente, é lícito ao juiz determinar que a situação seja esclarecida, com juntada de um eventual novo instrumento.

• A cautela indicada tem respaldo em princípios constitucionais de acesso à justiça, de proteção ao consumidor e de duração razoável do processo, harmonizando-se, ainda, com os postulados legais que privilegiam o julgamento de mérito e impõem o dever de cooperação entre os sujeitos do processo que, afinal, precisa ter desenvolvimento válido e regular.

• O risco de exigências judiciais excessivas, como de resto o de qualquer decisão judicial equivocada, constitui realidade inexpugnável, ínsita ao sistema de Justiça, mas que deve ser controlado pontualmente em cada processo, não podendo ser invocado como obstáculo à adoção de boas práticas na condução judicial do feito.

1. Nos termos do entendimento do Superior Tribunal de Justiça, a "ausência de legitimidade ativa, por se tratar de uma das condições da ação, é matéria de ordem pública cognoscível a qualquer tempo e grau, sendo insuscetível de preclusão nas instâncias ordinárias" (REsp 1.731.214/AL, relator Ministro Herman Benjamin, Segunda Turma, julgado em 8/5/2018, DJe de 19/11/2018). (AgInt no AgInt no AREsp n. 2.399.315/MA, relator Ministro Paulo Sérgio Domingues, Primeira Turma, julgado em 30/9/2024, DJe de 7/10/2024.)

2. VI. Na forma da jurisprudência dominante desta Corte, as questões de ordem pública, apreciáveis, de ofício, em qualquer tempo e grau de jurisdição, nas instâncias ordinárias (e.g., pressupostos processuais, condições da ação, decadência, prescrição, etc.), não se sujeitam à preclusão, podendo ser suscitadas, ainda que em sede de Embargos de Declaração. Precedentes [...] (EAREsp n. 146.473/ES, relatora Ministra Assusete Magalhães, Primeira Seção, julgado em 11/10/2023, DJe de 19/10/2023.)

Lei 9.507/97 (Lei do Habeas-data)

• Art. 8° A petição inicial, que deverá preencher os requisitos dos arts. 282 a 285 do Código de Processo Civil, será apresentada em duas vias, e os documentos que instruírem a primeira serão reproduzidos por cópia na segunda.

Parágrafo único. A petição inicial deverá ser instruída com prova:

I - da recusa ao acesso às informações ou do decurso de mais de dez dias sem decisão; (Recusa administrativa)

II - da recusa em fazer-se a retificação ou do decurso de mais de quinze dias, sem decisão; ou

III - da recusa em fazer-se a anotação a que se refere o § 2° do art. 4° ou do decurso de mais de quinze dias sem decisão.

• RE 631240 (Repercussão Geral - Tema 350)
• Órgão julgador: Tribunal Pleno
• Relator(a): Min. ROBERTO BARROSO
• Julgamento: 03/09/2014
• Publicação: 10/11/2014

Ementa Ementa: RECURSO EXTRAORDINÁRIO. REPERCUSSÃO GERAL. PRÉVIO REQUERIMENTO ADMINISTRATIVO E INTERESSE EM AGIR. 1. A instituição de condições para o regular exercício do direito de ação é compatível com o art. 5º, XXXV, da Constituição. Para se caracterizar a presença de interesse em agir, é preciso haver necessidade de ir a juízo. 2. A concessão de benefícios previdenciários depende de requerimento do interessado, não se caracterizando ameaça ou lesão a direito antes de sua apreciação e indeferimento pelo INSS, ou se excedido o prazo legal para sua análise. É bem de ver, no entanto, que a exigência de prévio requerimento não se confunde com o exaurimento das vias administrativas. 3. A exigência de prévio requerimento administrativo não deve prevalecer quando o entendimento da Administração for notória e reiteradamente contrário à postulação do segurado. 4. Na hipótese de pretensão de revisão, restabelecimento ou manutenção de benefício anteriormente concedido, considerando que o INSS tem o dever legal de conceder a prestação mais vantajosa possível, o pedido poderá ser formulado diretamente em juízo – salvo se depender da análise de matéria de fato ainda não levada ao conhecimento da Administração –, uma vez que, nesses casos, a conduta do INSS já configura o não acolhimento ao menos tácito da pretensão. 5. Tendo em vista a prolongada oscilação jurisprudencial na matéria, inclusive no Supremo Tribunal Federal, deve-se estabelecer uma fórmula de transição para lidar com as ações em curso, nos termos a seguir expostos. 6. Quanto às ações ajuizadas até a conclusão do presente julgamento (03.09.2014), sem que tenha havido prévio requerimento administrativo nas hipóteses em que exigível, será observado o seguinte: (i) caso a ação tenha sido ajuizada no âmbito de Juizado Itinerante, a ausência de anterior pedido administrativo não deverá implicar a extinção do feito; (ii) caso o INSS já tenha apresentado contestação de mérito, está caracterizado o interesse em agir pela resistência à pretensão; (iii) as demais ações que não se enquadrem nos itens (i) e (ii) ficarão sobrestadas, observando-se a sistemática a seguir. 7. Nas ações sobrestadas, o autor será intimado a dar entrada no pedido administrativo em 30 dias, sob pena de extinção do processo. Comprovada a postulação administrativa, o INSS será intimado a se manifestar acerca do pedido em até 90 dias, prazo dentro do qual a Autarquia deverá colher todas as provas eventualmente necessárias e proferir decisão. Se o pedido for acolhido administrativamente ou não puder ter o seu mérito analisado devido a razões imputáveis ao próprio requerente, extingue-se a ação. Do contrário, estará caracterizado o interesse em agir e o feito deverá prosseguir. 8. Em todos os casos acima – itens (i), (ii) e (iii) –, tanto a análise administrativa quanto a judicial deverão levar em conta a data do início da ação como data de entrada do requerimento, para todos os efeitos legais. 9. Recurso extraordinário a que se dá parcial provimento, reformando-se o acórdão recorrido para determinar a baixa dos autos ao juiz de primeiro grau, o qual deverá intimar a autora – que alega ser trabalhadora rural informal – a dar entrada no pedido administrativo em 30 dias, sob pena de extinção. Comprovada a postulação administrativa, o INSS será intimado para que, em 90 dias, colha as provas necessárias e profira decisão administrativa, considerando como data de entrada do requerimento a data do início da ação, para todos os efeitos legais. O resultado será comunicado ao juiz, que apreciará a subsistência ou não do interesse em agir.

Art. 217, Constituição Federal:

§ 1º O Poder Judiciário só admitirá ações relativas à disciplina e às competições desportivas após esgotarem-se as instâncias da justiça desportiva, regulada em lei.

• Informativo nº 749
• 19 de setembro de 2022.
• TERCEIRA TURMA
• Processo: HC 711.194-SP, Rel. Min. Marco Aurélio Bellizze, Rel. Acd. Min. Nancy Andrighi, Terceira Turma, por maioria, julgado em 21/06/2022, DJe 27/06/2022.

Ramo do Direito DIREITO PROCESSUAL CIVIL

TemaPaz, Justiça e Instituições Eficazes <br /> Medidas executivas atípicas. Medidas coercitivas. Apreensão de passaporte. Limitação temporal. Inexistência de duração pré-estabelecida. Verificação caso a caso.

Destaque - Não há um <u>tempo pré-estabelecido</u> fixamente para a duração da medida coercitiva atípica, que deve perdurar por tempo suficiente para dobrar a renitência do devedor.

Informações do Inteiro Teor - As medidas executivas atípicas, sobretudo as coercitivas, não são penalidades judiciais impostas ao devedor, pois, se assim fossem, implicariam obrigatoriamente em quitação da dívida após o cumprimento da referida pena, o que não ocorre.

• Por esse motivo, é correto dizer que essas medidas também não representam uma superação do dogma da patrimonialidade da execução, uma vez que são os bens - e apenas os bens - do devedor que respondem pelas suas dívidas. Não se deve confundir, todavia, patrimonialidade da execução com a possibilidade de imposição de restrições pessoais como método para dobrar a recalcitrância do devedor.

• De fato, essas medidas devem ser deferidas e mantidas enquanto conseguirem operar, sobre o devedor, restrições pessoais capazes de incomodar e suficientes para tirá-lo da zona de conforto, especialmente no que se refere aos seus deleites, aos seus banquetes, aos seus prazeres e aos seus luxos, todos bancados pelos credores.

• A limitação temporal das medidas coercitivas atípicas, a propósito, é questão inédita nesta Corte, pois os precedentes até aqui examinados se circunscreveram aos pressupostos para deferimento de medidas dessa natureza, mas não às hipóteses de manutenção e de verificação de efetividade após o transcurso de determinado período.

• Feitas estas considerações. é correto afirmar que não há uma formula mágica e nem deve haver um tempo pré-estabelecido fixamente para a duração de uma medida coercitiva, que deve perdurar, pois, pelo tempo suficiente para dobrar a renitência do devedor, de modo a efetivamente convencê-lo de que é mais vantajoso adimplir a obrigação do que, por exemplo, não poder realizar viagens internacionais.

• No que tange ao bloqueio de passaporte, observa-se o peculiar e injustificado interesse que os devedores que afirmam estar em situação de miserabilidade, de insolvência ou de qualquer modo impossibilitados de adimplir as suas dívidas, possuem especificamente na posse desse documento.

• Isso porque ou bem o devedor realmente se encontra em situação de penúria financeira e não reúne condições de satisfazer a dívida (e, nessa hipótese, a suspensão do passaporte será duplamente inócua, como técnica coercitiva e porque o documento apenas ficará sob a posse do devedor no Brasil, diante da impossibilidade de custear viagens internacionais) ou o devedor está realmente ocultando patrimônio e terá revogada a suspensão tão logo quite as suas dívidas.

Note de Synthèse : Rapport sur la Santé Mentale des Mineurs

Le rapport: https://hyp.is/go?url=https%3A%2F%2Fwww.assemblee-nationale.fr%2Fdyn%2F17%2Frapports%2Fdde%2Fl17b1700_rapport-information.pdf&group=world

Résumé

Ce document de synthèse présente les conclusions et recommandations clés du rapport parlementaire sur la santé mentale des mineurs.

Le constat principal est une dégradation alarmante de la santé psychique des enfants et adolescents en France, avec 1,6 million de mineurs souffrant d'un trouble psychique, et une augmentation particulièrement marquée de +70% chez les 10-14 ans entre 2017 et 2023.

Le système de soins est totalement débordé, avec seulement un jeune sur deux ayant accès à un suivi et des délais d'attente atteignant 18 mois pour un premier rendez-vous en Centre Médico-Psychologique (CMP).

Le rapport identifie deux crises interdépendantes : d'une part, une offre de soins illisible, sous-financée et en manque criant de personnel, et d'autre part, une prévention quasi inexistante, notamment dans le cadre scolaire.

Une surreprésentation dramatique des enfants de l'Aide Sociale à l'Enfance (ASE) au sein des services de pédopsychiatrie (jusqu'à 40% des lits pour 2% de la population mineure) met en lumière la faillite du suivi de ces publics particulièrement vulnérables.

Les 54 recommandations formulées visent à une refonte structurelle du système. Les priorités incluent :

1. La réorganisation du parcours de soins via une "gradation" claire, renforçant le premier recours (médecins généralistes, pédiatres) pour désengorger les CMP.

2. Le renforcement des CMP comme pivots du système, avec des budgets pérennes, un maillage territorial assurant un accès en 30 minutes, et une approche pluridisciplinaire.

3. L'investissement massif dans la prévention, de la périnatalité (unités parents-bébés) à la santé scolaire (atteindre les ratios européens de médecins et psychologues).

4. Une meilleure prise en charge des enfants de l'ASE avec un repérage systématique, un suivi de santé effectif et la création de structures mixtes soin-hébergement.

5. La lutte contre la pénurie de professionnels par la revalorisation des salaires, la réforme de la tarification des actes et des mesures pour améliorer l'attractivité de la pédopsychiatrie.

Enfin, le rapport souligne l'impact majeur de facteurs environnementaux comme la pression scolaire (Parcoursup), l'addiction aux écrans et les inégalités sociales, appelant à des réponses politiques plus larges.

1. Le Constat Alarmant d'une Crise de Santé Publique

Le rapport parlementaire, fruit de six mois de travail incluant 37 auditions et quatre déplacements, dresse un tableau sans équivoque de la détérioration de la santé mentale des mineurs en France.

A. Chiffres Clés de la Dégradation

• Prévalence des troubles : Selon le rapport de la Cour des comptes de 2023, 1,6 million d'enfants et d'adolescents souffrent d'un trouble psychique.

• Augmentation significative : Entre 2017 et 2023, une forte augmentation des troubles a été observée, notamment :

◦ +70 % chez les 10-14 ans.    ◦ +46 % chez les 15-20 ans.

• Actes auto-infligés : La DREES note une augmentation des hospitalisations pour tentatives de suicide et gestes auto-infligés chez les 10-14 ans.

• Précocité des troubles : La moitié des troubles psychiatriques se déclarent avant l'âge de 15 ans, soulignant l'urgence d'une intervention précoce.

B. La Vulnérabilité Extrême des Enfants Protégés

Un des constats les plus marquants du rapport est la surreprésentation des enfants relevant de l'Aide Sociale à l'Enfance (ASE) dans les services de pédopsychiatrie.

• Occupation des lits : Jusqu'à 40-50 % des lits d'hospitalisation à temps plein sont occupés par des enfants placés, alors qu'ils ne représentent que 2 % des mineurs en France.

• Facteurs de risque : La maltraitance subie par ces enfants multiplie par deux les risques de suicide et par quatre les risques de psychotrauma.

• Cercle vicieux : Le suivi médical défaillant de ces mineurs entraîne une prise en charge trop tardive, souvent via une hospitalisation prolongée qui se substitue à un lieu de vie, aggravant leur état.

En parallèle, les foyers sont démunis face à des jeunes avec des troubles lourds non pris en charge.

2. Un Système de Soins Débordé et Illisible

Face à la hausse de la demande, l'offre de soins est criante de manque de moyens et d'organisation, laissant de nombreuses familles sans solution.

A. La Saturation des Structures

• Accès aux soins limité : Sur les 1,6 million de jeunes présentant des troubles, seuls 750 000 à 850 000 sont suivis, soit environ un sur deux.

• Délais d'attente insoutenables : L'attente pour un premier rendez-vous en Centre Médico-Psychologique (CMP) peut atteindre 12 à 18 mois, parfois plus.

Cette attente laisse le temps à la situation de s'aggraver, conduisant à une prise en charge aux urgences, elles-mêmes engorgées.

B. Recommandation : Instaurer une Gradation des Soins

Pour rendre l'offre plus lisible et efficiente, le rapport préconise une meilleure organisation du parcours de soins.

• Premier niveau : Les médecins généralistes et pédiatres devraient assurer la première consultation, la détection et l'orientation.

Cela nécessite un renforcement de leur formation en psychiatrie infanto-juvénile.

Ce niveau pourrait aussi inclure des psychologues et les Maisons des Adolescents.

• Deuxième niveau (pivot) : Les Centres Médico-Psychologiques (CMP) se concentreraient sur les cas nécessitant une expertise pluridisciplinaire, tout en conservant un accueil inconditionnel sans adressage obligatoire pour ne pas éloigner les plus fragiles.

• Troisième niveau : Des centres de gestion de crise de courte durée, adossés aux urgences pédiatriques ou hôpitaux psychiatriques, pour les situations les plus aiguës.

C. Recommandation : Renforcer le Secteur de la Pédopsychiatrie

Le rapport insiste sur la nécessité de renforcer l'existant plutôt que de disperser les moyens dans des dispositifs innovants non pérennes.

• Stabilité financière : Pérenniser et flécher les budgets de la pédopsychiatrie au sein des hôpitaux et privilégier les dotations pluriannuelles aux appels à projets.

• Priorité au soin : Réorienter les moyens financiers et humains vers le soin direct plutôt que vers des plateformes de diagnostic qui, malgré leurs avancées, peuvent favoriser une approche médicamenteuse au détriment de la relation thérapeutique.

• Maillage territorial : Revoir le maillage des CMP pour que chaque enfant puisse y accéder en moins de 30 minutes de son domicile, en adaptant le découpage des secteurs aux évolutions démographiques (un secteur couvre aujourd'hui jusqu'à 500 000 habitants contre 200 000 prévus initialement).

3. L'Urgence d'une Prévention Efficace

Le rapport souligne que la prévention est le parent pauvre de la politique de santé mentale, alors qu'elle est déterminante.

A. La Période des 1000 Premiers Jours

La période allant de la conception aux deux ans de l'enfant est fondamentale.

• Soutien à la parentalité : Les "Maisons des bébés" sont des dispositifs essentiels pour prévenir les troubles précoces du lien parent-enfant.

• Psychiatrie périnatale : Les unités d'hospitalisation conjointe mère-bébé, comme celle de Toulouse, permettent de détecter les signes de souffrance dès les premiers jours et de réparer le lien d'attachement. Il est recommandé de développer ces unités et de former les professionnels à la théorie de l'attachement.

B. Le Rôle Fondamental de la Santé Scolaire

L'Éducation Nationale est un lieu stratégique pour la détection précoce, mais ses moyens sont gravement fragilisés.

Professionnel

Ratio Actuel

Ratio Recommandé (UE)

Recommandation du Rapport

Psychologue scolaire

1 pour 1 600 élèves

1 pour 800 élèves

1 pour 800 élèves

Médecin scolaire

1 pour 13 000 élèves

-

1 pour 5 000 élèves

Infirmier scolaire

1 pour 9 établissements

-

1 par établissement

• Conséquence directe : Le bilan de santé obligatoire à 6 ans est réalisé à 12 ans dans 80 % des cas, entraînant une accumulation de difficultés non détectées à l'entrée au collège.

Le rapport préconise une trajectoire de recrutement ambitieuse pour atteindre les ratios cibles.

4. La Crise des Ressources Humaines et la Question de l'Attractivité

La pénurie de professionnels qualifiés est au cœur de la crise du système.

• Pénurie de pédopsychiatres : La densité nationale est de 6,7 pédopsychiatres pour 100 000 jeunes, et la profession est vieillissante (moyenne d'âge de 60 ans).

La discipline est peu attractive pour les internes (127 inscrits pour 157 postes ouverts en 2023) car jugée trop proche des sciences humaines et aux conditions de travail difficiles.

• Manque de valorisation : Les professions (psychologues, paramédicaux) sont peu valorisées et faiblement rémunérées.

Une consultation en pédopsychiatrie est un acte long et complexe (minimum 1h) mais rémunéré seulement 67 € en moyenne, poussant les professionnels vers le secteur non conventionné ou la patientèle adulte.

• Recommandations :

• ◦ Revaloriser la rémunération des psychologues et personnels paramédicaux en CMP.  

• ◦ Augmenter significativement le tarif des consultations en pédopsychiatrie.  

• ◦ Réformer le codage des actes pour valoriser le temps de concertation avec les familles et partenaires. 

• ◦ Instaurer un quotient départemental pour les stages en internat afin de mieux répartir les futurs médecins sur le territoire.

5. Facteurs Environnementaux et Sociétaux Aggravants

Le rapport identifie plusieurs facteurs externes qui pèsent lourdement sur la santé mentale des jeunes.

• Médicalisation excessive : La consommation de psychotropes (type Ritaline) est en forte augmentation (490 000 enfants de 3 à 17 ans concernés).

Ces médicaments sont souvent prescrits par des médecins généralistes peu formés, posant la question du bon usage.

Le rapport recommande de privilégier les soins thérapeutiques à la prescription.

• Impact des écrans : L'addiction aux écrans et l'exposition à des contenus violents, pornographiques ou au cyberharcèlement sont unanimement citées comme aggravant les troubles anxio-dépressifs.

Le rapport soutient la majorité numérique, la mise en place de "pauses numériques" dans les établissements scolaires et appelle à des campagnes de prévention massives.

• Pression scolaire : Le système d'orientation, et notamment Parcoursup, est décrit comme créant un "climat extrêmement anxiogène".

Les rapporteurs proposent, avec des nuances, de réformer en profondeur (Nathalie Colin-Osterlé) ou de supprimer (autre rapporteure) ce dispositif et toute forme de sélection à l'université.

• Déterminants sociaux : Les enfants de familles défavorisées ont un risque trois fois plus important de développer un trouble mental et ont plus de difficultés d'accès aux soins.

Le rapport appelle à investir dans les services publics et les politiques de lutte contre les inégalités sociales pour agir sur les causes profondes.

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