I actually hit this recently with a Google Docs generated PDF (print -> download) that wasn't rendering correctly in Chrome or Firefox, but did load as expected in Edge.
Reasons are mainly: No incentive to develop antibiotics from a legal perspective (FDA), as insurance companies prefer to reimburse the cheap and generic, still working mostly "well enough" for now.
Insurers pay for in-patient antibiotics as part of a lump sum to hospitals known as a Diagnosis Related Group (DRG). Using a cheap antibiotic increases hospital profit margins, while using an expensive new drug could mean that a hospital might lose money by treating a given patient. As a result, hospitals are incentivized to use cheaper antibiotics whenever possible. This puts significant pricing pressure on new antibiotics, which are one of the only type of medicines paid for like this.
Isn’t the grit literature just Angela Duckworth rediscovering conscientiousness?
> Much Ado about Grit: A Meta-Analytic Synthesis of the Grit Literature
> Grit has been presented as a higher-order personality trait that is highly predictive of both success and performance and distinct from other traits such as conscientiousness. This paper provides a meta-analytic review of the grit literature with a particular focus on the structure of grit and the relation between grit and performance, retention, conscientiousness, cognitive ability, and demographic variables. Our results based on 584 effect sizes from 88 independent samples representing 66,807 individuals indicate that the higher-order structure of grit is not confirmed, that grit is only moderately correlated with performance and retention, and that grit is very strongly correlated with conscientiousness. We also find that the perseverance of effort facet has significantly stronger criterion validities than the consistency of interest facet and that perseverance of effort explains variance in academic performance even after controlling for conscientiousness. In aggregate our results suggest that interventions designed to enhance grit may only have weak effects on performance and success, that the construct validity of grit is in question, and that the primary utility of the grit construct may lie in the perseverance facet.
Keywords: grit; performance; meta-analysis; perseverance of effort; consistency of interest
> Predicting school success: Comparing Conscientiousness, Grit, and Emotion Regulation Ability
> The present paper examines validity of three proposed self-regulation predictors of school outcomes – Conscientiousness, Grit and Emotion Regulation Ability (ERA). In a sample of private high school students (N = 213) we measured these constructs along with indices of school success obtained from records (rule violating behavior, academic recognitions, honors, and GPA) and self-reported satisfaction with school. Regression analyses showed that after controlling for other Big Five traits, all school outcomes were significantly predicted by Conscientiousness and ERA, but not Grit. The discussion focuses on the impor- tance of broad personality traits (Conscientiousness; measure of typical performance) and self-regulation abilities (ERA; measure of maximal performance) in predicting school success.
People can work really hard at doing a crap job. Doing the job right makes more sense to determine positive outcomes. Having some academic shreds to back up the common sense is good too.
I worked a few years in pharma R&D (Roche, largest R&D budget in this industry).
In a pharma setting, the 3D structure of a protein is mostly used to perform drug design (https://en.wikipedia.org/wiki/Drug_design#Computer-aided_dru...), i.e. trying to understand how a chemical will physically interact with a protein and thereby modify it's physiological function, in order to treat a disease.
The biggest problem comes from the fact that proteins are (1) non-static and very flexible and (2) don't exist in vacuum, they interact with a myriad of other entities in a living system. In other words, it's not because you know the structure of a protein and how to theoretically perturb it with a small molecule, that you have a drug. The large majority of structures predicted to be active against a protein target are not, when tested in a biological assay. The process helps, but ultimately it's a very empirical endeavor (test a ton of different chemicals in actual experiments, try to abstract some logic and move on from that). As a result, simply knowing the structure of a protein will not get you far down the line into finding a new drug.
On the resource topic: Even in a very large pharma setting, you will find only a dozen of scientists or so dedicated to the topic (out of tens of thousands employees), supporting many projects and with very little time to perform their own research. As a result, any team fully dedicated to the problem (like AlphaFold) can easily over-compete pharma. Most of the cost in drug discovery comes from dealing with patients and clinical trial. It's only at this stage that you'll know how your drug really works, and how it fits in the existing market and society (think of neuroscience for instance).
I don't want to undermine the protein structure field and AlphaFold results (it's fascinating), but pharma business model de facto relies very little on knowing a protein structure or not. It's also mostly useful to design small molecules, a class a bit out of fashion (biologics are the top-sellers in 2018, and new modalities are coming-up, like RNAs and gene editing for instance).
This is true, and big pharma will continue to invest very heavily here, since these medications contain living organisms and are much harder/more expensive to make into "generic" versions.
Biologics do not contain living organisms. For example monoclonal antibodies are considered biologics and are not alive, they can also easily be made “generic”.
Nano-bubbles and particles have been used since a long time to diagnose diseases and enhance the quality of ultrasound analysis (contrast agents). You can also link an antibody on their surface to target them against a particular protein or reveal a zone of interest (e.g. a tumor revealed by a specific biomarker). Nano-bubbles are even use to destroy adjacent tissue on purpose (sonoporation).
Usually such particles are constructed via a mix of lipids and have a very short life time in the blood stream. I wonder how they're going to keep them alive in the blood stream for what seems to be a very long time and their design regarding toxicity.
