13 Matching Annotations
  1. Oct 2024
    1. Disease: Von Willebrand Disease (VWD) Type 2A

      Patient: 31 yo, Female

      Variant1: VWF NC_000012.12: c.875-5T>Gdel, p.(Ser292_Glu333delinsLys) Causes complete exon 8 skipping

      Variant2: VWF NM_000552.5: c.813C>G, p.(Tyr271*)

      Phenotypes: History of bleeding (epistaxis, uncontrollable by conventional hemostatic treatment), Easy bruising, gum bleeding, excessive menstrual bleeding, mild decrease in plasma VWF:Ag, severe impairment in VWF function, VWF:Ab/VWF:Ag ratio decreased, VWF:CB/VWF:Ag ratio decreased, FVIII:C lvs slighly below normal range

      Family: Son had bleeding diathesis and spontaneous epistaxis (less severe than proband), normal parents

      In silico data available: SpliceAI delta score of 0.51 for loss of splice acceptor caused by variant 1

      Alamut showed small to moderate effects of the variant on normal splicing of VWF

      NetGene2 showed weak strength of 3' splice sites in exon 8

      SpliceAid2 showed TIA-1 and TIAL 1, which bind to U-rich motifs and facilitate 5' splice site recognition where destroyed in the mutated sequence

  2. Sep 2024
  3. Nov 2023
    1. if you look at somewhere like the UK 75% of all our flights are made by just 15% of the population and we know who that 15% are you know they're not the average person or the poor person so we're not talking about 00:12:49 someone who flies occasionally away on holiday we're talking about people who fly really regularly they have their second homes they have their big mansions they have their large cars and this particular group all of those 00:13:02 things will have to change
      • for: elites - lifestyle change, great simplification, worldview transition -materially-excessive and wonder-poor to materially- sufficient and wonder-rich, awakening wonder, Deep Humanity, BEing journeys

      • comment

      • possible way to have more than one home
      • a group can co-create and mutually invest in a regenerative timeshare
        • an example is to co-invest in a regenerative local community economy based around a regerative agroforestry system which has community owned and supported agriculture with year round Regenerative work and sustainable accommodations
        • Deep Humanity BEing journeys can play a role to re-awaken wonder
  4. Mar 2023
    1. We can no longer ignore the fact that the pursuit of the goodlife can impact the chances of others to live a good life.

      // - This becomes a moral and ethical question, indeed could it become a legal question? - If excessive wealth, leading to excessive personal carbon emissions and denial of the wellbeing of others, limiting the freedom of others, does this not constitute harm? - If the law is about preventing harm, then extreme wealth with adverse social impacts on many others could be construed and theoretically considered as a potential form of societal harm and hence come under legal considerations. - in other words, some forms of excessive wealth could be construed as harmful wealth - excessive wealth, as it exists today, could have unintended consequences of bringing about societal harm - excessive wealth is potentially a large progress trap

  5. Feb 2023
  6. Jan 2022
    1. ``We've learned and struggled for a few years here figuring out how to make a decent phone,'' he said. ``PC guys are not going to just figure this out. They're not going to just walk in.''

      Sounds very different from the verbatim:

      Yeah. And so I just would caution people that think they’re going to walk in here and just and do these. We’ve struggled for a few years here, figuring out how to make a decent phone. The PC guys are not going to just, you know, knock this out. I guarantee it. So, look, welcome, let’s go for it. We can’t stop all that. It’s going to happen, but it’s going to be, I don’t think it’ll be so easy for everybody, as everybody thinks to enter it. It’s a tough space.

    1. Colligan: Yeah. And so I just would caution people that think they’re going to walk in here and just and do these. We’ve struggled for a few years here, figuring out how to make a decent phone. The PC guys are not going to just, you know, knock this out. I guarantee it. So, look, welcome, let’s go for it. We can’t stop all that. It’s going to happen, but it’s going to be, I don’t think it’ll be so easy for everybody, as everybody thinks to enter it. It’s a tough space.

      Indeed, quite different from the paraphrase in that report

      We've learned and struggled for a few years here figuring out how to make a decent phone,'' he said.PC guys are not going to just figure this out. They're not going to just walk in.''

  7. Sep 2021
    1. there has been a spectacular rise in luxury consumption, with the consumption patterns of the global elite acting as a marker for those further down the income scale. Robert Frank (2000) describes the process as 'luxury fever', as consumption expectations are ratcheted up all the way down the income scale. The global elite are pushing up people's expectations and assumptions. In the US, for example, the average size of house has doubled, in square feet terms, in the past thirty years. In part it is a function of the positional nature of consumption. We consume in order to position ourselves relative to other people. Not only do the global elite raise the upper limit, everyone is thus forced to spend more just to keep up, but they also become the perceived benchmark, Juliet Schor's work, for example, shows that people are no longer keeping up with the people next door, but the people they see on television and magazines (Schor, 1998). In order to keep up with these raised consumption standards people are working harder and longer as well as taking out more debt. The increase in luxury consumption has raised consumption expectations further down the income scale, which in order to be funded has involved increased workloads and increased indebtedness. It is not so much keeping up with the Jones but 'keeping up with the Gates'.

      The elites point the way for those in even the lowest income brackets to follow. This crosses cultures as well. Capitalism trumps colonialism as former colonized peoples reserve the right to taste the fruits of capitalism. Hence, hard work, ingenuity and leveraging opportunity to accumulate all the signs and symbols of wealth, joining the colonialist biased elites is seen as having arrived at success, even though it means contributing to the destruction of the planetary commons. The aspirations to wealth must be uniformly deprioritized in order to align our culture in the right direction that will rescue our species from the impact of following this misdirection for the past century.

  8. Oct 2020
    1. Take responsibility for your outgoing network traffic If you install software that interacts with other sites over the network, you should be aware how it works and what kind of traffic it generates. If it has the potential to make thousands of requests to other sites, make sure it uses an HTTP cache to prevent inflicting abuse on other sites.
    1. It is not appropriate to use these document types for live content. These are made available only for download, to support local use in development, evaluation, and validation tools. Using these versions directly from the W3C server could cause automatic blockage, preventing them from loading. If it is necessary to use schemata in content, follow guidelines to avoid excessive DTD traffic. For instance, use caching proxies to avoid fetching the schema each time it is used, or ensure software uses a local cache, such as with XML catalogs.
  9. Jun 2020
  10. Apr 2020