24 Matching Annotations
  1. Jun 2020
    1. Then there’s the increasingly fluid and expanding nature of the jobs we do, which increases our need to learn more and adapt quickly. All of these factors combined can result in overload, confusion and serious obstacles to progress. The very information that should be helping us, is creating a barrier to learning. There’s simply too much to read and not enough time to read it.

      Information overload

    1. NA-based vaccines like the one being developed by the Jenner Institute may have problems like randomly integrating with the host cell chromosome and resulting in a recombination of genes. He says pioneers in adenovirus technology in the US, who have explored the technology very well, expressed their limitations, which was also the reason it was not tried successfully even in gene therapy

      Difficulty for SNA based vaccines

    2. dengue vaccine Dengvaxia spearheaded by French drug maker Sanofi. The vaccine was introduced after two decades of research and hundreds of millions of dollars in investments. But it was not received well as it led to unexpected events like inducing a higher risk of contracting the disease in a group of children in Philippines. Similarly, Merck of US had to wound up a large-scale clinical trial on a HIV vaccine after data showed it may backfire and make people more vulnerable to the disease.

      Failures of different vaccines.

    3. The quickest that a vaccine has been developed is the Ebola vaccine branded Ervebo that was granted an approval by the USFDA only last year, four years after the dreaded disease reared its head in parts of west Africa.

      Lots of difficulties

    4. . According to published reports, the vaccine being developed uses a replication-deficient adenovirus (a harmless virus) to deliver a SARS-CoV-2 protein to induce a protective immune response. Coded as ChAdOx1, the same vaccine has been used against several other pathogens, including one for the Mers virus.

      Still nothing in sight!

    5. Kang cited how the BCG vaccine underwent as many as 200 sub-cultures before it was considered attenuated (weakened) enough for human use. Another leading virologist tells ET Prime that Moderna is in an uncharted territory and no vaccine using that technology has reached the licensing stage.

      Requires significant attenuation before you actually see results.

    6. Known as messenger RNA, Moderna’s vaccine essentially aims to induce an immune response by sending instruction signals for a spike protein located on the surface of the virus. These immune cells are then expected to develop antibodies against the virus whenever a person contracts the coronavirus. Although promising, this pathway has not been successful or used to develop vaccines before.

      Novel form of vaccine but not entirely worth it.

    7. Moderna had earlier announced that it would start its pivotal phase III studies in July, to be followed by a biologic-licence application (BLA) with the USFDA. While apprehensions have been raised over that timeline, senior researchers like Fauci who had backed Moderna’s vaccine have not made any observations on the quality of data shared.

      Very bad quality of data

    8. For example, on May 18, Moderna shared data showing that eight persons who were administered its vaccine coded mRNA-1273 elicited neutralising antibodies against the novel coronavirus. Moderna’s is an exceptional case in the history of vaccine development. In a rather unusual twist, the vaccine skipped animal studies, a pre-requisite, before it was tested on humans.
    9. He passionately explains how his team developed a reverse-genetics system against a poultry virus called avian paramyxovirus. In simple terms, this is a method of recovering a virus, manipulating its genome, and using it as a vector to induce an immune response.
    10. A few days ago, the US launched a public-private partnership under Operation Warp Speed that hand-picked five companies that can develop and make vaccines, diagnostics, and therapeutics on an accelerated basis.
    11. Tests on patients showed that remdesivir helped shrink the recovery time for critical patients from 15 days to 11 days but could not prevent mortality or bring down death rates. In short, remdesivir isn’t a definitive cure for Covid-19.
    12. Hundreds of chemistry-based and biological drugs – new and existing – are being tested everyday across continents to rein in the coronavirus, but so far only one has shown partial activity.
    1. Cochrane meta-analysis, however, came to similar conclusions as the VA study, showing no difference in overall survival.

      de Castria TB, da Silva EM, Gois AF, and Riera R: Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst Rev 2013

    2. Most recently, a National Cancer Database (NCDB) study compared the effect of PORT in patients with N2 disease. The use of PORT resulted in a significant improvement in 5-year OS (27.8 vs. 34.1%, p < 0.001).

      Corso CD, Rutter CE, Wilson LD, et al: Re-evaluation of the role of postoperative radiotherapy and the impact of radiation dose for non-small-cell lung cancer using the National Cancer Database. J Thorac Oncol 2015; 10: pp. 148-155

    3. A combined analysis of two of these trials, the STARS and ROSEL trials, was recently reported. Combined eligibility included those with a tumor less than 4 cm, with the surgical arm requiring a lobectomy and mediastinal lymph node sampling. Central tumors were allowed on the STARS protocol, while only peripheral tumors were enrolled on the ROSEL protocol. SBRT regimens included 54 Gy in 3 fractions, 50 Gy in 4 fractions or 60 Gy in 5 fractions. A total of 58 patients were randomized; after a median follow-up of 40 months, SBRT was noted to have superior OS (3-year OS, 95% vs. 79%, p = 0.04) but similar rates of local, regional, and distant recurrence-free survival

      Chang JY, Senan S, Paul MA, et al: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015; 16: pp. 630-637

    4. Patterns of pathological mediastinal lymph node involvement based on the involved lobe have been described. In one such study, right upper lobe tumors most commonly spread to the ipsilateral lower paratracheal nodes, while right middle and right lower lobe tumors had similar distributions of paratracheal and subcarinal nodal involvement

      Asamura H, Nakayama H, Kondo H, et al: Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis. J Thorac Cardiovasc Surg 1999; 117: pp. 1102-1111

    5. Thyroid transcription factor-1 (TTF-1) and napsin are characteristic of primary adenocarcinoma of the lung in which cytokeratin (CK) 7 is usually positive and CK 20 is negative. Squamous cell carcinomas will usually stain positive for p40, CK 5/6, and/or p63. Typical neuroendocrine markers include chromogranin A, synaptophysin, neuron-specific enolase and cluster of differentiation (CD) 56. In some tumors, especially when biopsy material is limited, it may not be possible to characterize histological type and the term NSCLC not otherwise specified (NOS) may be applied.

      Important markers- TTF-1, Napsin, CK-7 usually negative for CK20.

    6. useful metric in quantifying this exposure is known as pack years smoked , which is the amount of packs per day multiplied by the length of time in years smoking. Up to 90% of the risk attributable to tobacco exposure can be avoided with early tobacco cessation.

      Peto R, Darby S, Deo H, et al: Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies. BMJ 2000; 321: pp. 323-329

  2. May 2020
    1. Once a jumbled shop, it now resembles an organized ministore, complete with red and blue JioMart branding. Customers can place orders for items such as salt and lentils via a JioMart WhatsApp account. The orders come to the shop and the items are then delivered and paid for in cash. Reliance is also providing a manager and free deliveries.

      The last mile delivery will be a huge issue.

    2. Reliance last year paid about 350,000 rupees ($4,600) to overhaul the space, according to a person familiar with the matter. The shop owner will pay Reliance back in installments over six years.

      This explains its well

    3. Information reviewed by The Wall Street Journal regarding one small shop participating in a trial shows how Reliance’s vision—and willingness to spend now to reap future gains—is taking shape.

      This is odd though. Perhaps related to the Facebook storefronts announced.

  3. Oct 2019
    1. “Using open annotation to bring reviews to preprints takes full advantage of its promise, namely the ability to layer diverse perspectives over original documents for the benefit of all,” said Dan Whaley, Founder of Hypothesis. “The scholarly process can only benefit when researchers can immediately know what they previously had no easy way to discover.”

      You can add comments to the annotations.

    2. eLife and the EMBO Press journals, together with Peerage of Science and Review Commons, two journal-independent peer review initiatives, will be the first to participate. Several other groups plan to join the pilot later, including the American Society of Plant Biologists (ASPB) and the Public Library of Science (PLOS).

      It makes sense but there is no way you can export the annotations out of the service.