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"Martin, S"
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The Macroeconomics of Epidemics
We extend the canonical epidemiology model to study the interaction between economic decisions and epidemics. Our model implies that people cut back on consumption and work to reduce the chances of being infected. These decisions reduce the severity of the epidemic but exacerbate the size of the associated recession. The competitive equilibrium is not socially optimal because infected people do not fully internalize the effect of their economic decisions on the spread of the virus. In our benchmark model, the best simple containment policy increases the severity of the recession but saves roughly half a million lives in the United States.
Journal Article
Population structure in genetic studies: Confounding factors and mixed models
A genome-wide association study (GWAS) seeks to identify genetic variants that contribute to the development and progression of a specific disease. Over the past 10 years, new approaches using mixed models have emerged to mitigate the deleterious effects of population structure and relatedness in association studies. However, developing GWAS techniques to accurately test for association while correcting for population structure is a computational and statistical challenge. Using laboratory mouse strains as an example, our review characterizes the problem of population structure in association studies and describes how it can cause false positive associations. We then motivate mixed models in the context of unmodeled factors.
Journal Article
Augmented reality
\"Augmented Reality combines computer technology with real world experiences. With the use of advanced screen sensors and computer created overlays, real-life environments are transformed into high-tech surroundings. Describes the opportunities and challenges associated with developing this highly technical innovation. Includes a glossary, websites, and bibliography for further reading\"-- Provided by publisher.
Book
DEBATE: Do interventions based on behavioral theory work in the real world?
Background
Behavioral scientists suggest that for behavior change interventions to work effectively, and deliver population-level health outcomes, they must be underpinned by behavioral theory. However, despite implementation of such interventions, population levels of both health outcomes and linked behaviors have remained relatively static. We debate the extent to which interventions based on behavioral theory work in the real world to address population health outcomes.
Discussion
Hagger argues there is substantive evidence supporting the efficacy and effectiveness of interventions based on behavioral theory in promoting population-level health behavior change in the ‘real world’. However, large-scale effectiveness trials within existing networks are relatively scarce, and more are needed leveraging insights from implementation science. Importantly, sustained investment in effective behavioral interventions is needed, and behavioral scientists should engage in greater advocacy to persuade gatekeepers to invest in behavioral interventions.
Weed argues there is no evidence to demonstrate behavioral theory interventions are genuinely effective in real world settings in populations that are offered them: they are merely efficacious for those that receive them. Despite behavioral volatility that is a normal part of maintaining steady-state population behavior levels creating the illusion of effectiveness, interventions fail in shifting the curve of population behaviors because they focus on individuals rather than populations.
Hagger responds that behavioral interventions work in the ‘real world’ in spite of, not because of, flux in health behaviors, and that the contention that behavioral theory focuses solely on individual behavior change is inaccurate.
Weed responds that the focus on extending the controls of efficacy trials into implementation is impractical, uneconomic and futile, and this has squandered opportunities to conduct genuine effectiveness trials in naturalistic settings.
Summary
Hagger contends that interventions based on behavioral theory are effective in changing population-level behavior in ‘real world’ contexts, but more evidence on how best to implement them and how to engage policymakers and practitioners to provide sustained funding is needed. Weed argues for a paradigm shift, away from aggregative attempts to effect individual behavior change towards a focus on disrupting social practices, underpinned by understanding social and economic causation of the distribution and acceptance of behaviors in a population.
Journal Article
Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
A motif was identified in the scaffold of an (
S
)-selective transaminase that enables the asymmetric synthesis of bulky chiral amines. This motif is transferable to other enzymes with as low as 70% sequence identity. The biocatalysts developed show high stereoselectivity and their synthetic potential was confirmed in preparative scale synthesis.
Journal Article
Clinical Utility of Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is characterized by substantial genetic and phenotypic heterogeneity, leading to considerable diversity in clinical course including the most common cause of sudden death in young people and a determinant of heart failure symptoms in patients of any age. Traditionally, two-dimensional echocardiography has been the most reliable method for establishing a clinical diagnosis of HCM. However, cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as a technique particularly well suited to characterize the diverse phenotypic expression of this complex disease. For example, CMR is often superior to echocardiography for HCM diagnosis, by identifying areas of segmental hypertrophy (ie., anterolateral wall or apex) not reliably visualized by echocardiography (or underestimated in terms of extent). High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected), end-stage systolic dysfunction, and massive LV hypertrophy. CMR observations also suggest that the cardiomyopathic process in HCM is more diffuse than previously regarded, extending beyond the LV myocardium to include thickening of the right ventricular wall as well as substantial morphologic diversity with regard to papillary muscles and mitral valve. These findings have implications for management strategies in patients undergoing invasive septal reduction therapy. Among HCM family members, CMR has identified unique phenotypic markers of affected genetic status in the absence of LV hypertrophy including: myocardial crypts, elongated mitral valve leaflets and late gadolinium enhancement.
The unique capability of contrast-enhanced CMR with late gadolinium enhancement to identify myocardial fibrosis has raised the expectation that this may represent a novel marker, which may enhance risk stratification. At this time, late gadolinium enhancement appears to be an important determinant of adverse LV remodeling associated with systolic dysfunction. However, the predictive significance of LGE for sudden death is incompletely resolved and ultimately future large prospective studies may provide greater insights into this issue. These observations underscore an important role for CMR in the contemporary assessment of patients with HCM, providing important information impacting diagnosis and clinical management strategies.
Journal Article