An investigation into statins, PCSK9 inhibitors, and other current cholesterol treatments

Hypercholesterolemia is one of the most prevalent, yet underdiagnosed diseases faced by the medical community today. Its prevalence can largely be attributed to diet, lack of exercise, and lifestyle choices such as smoking or drinking, but there is also a genetic component. Familial Hypercholesterolemia is the genetic disorder in which a person is unable to properly eliminate levels of low-density lipoprotein, mostly due to an ineffective receptor in the liver. Hypercholesterolemia has been positively correlated with the prevalence of cardiovascular disease, and patients with the severe homozygous familial hypercholesterolemia typically have abbreviated lifespans. In these situations, and also those less acutely dire, it’s necessary to rely on medication to help maintain one’s cholesterol levels to within low risk ranges. High does statin therapy has been shown to be the most effective therapy for maintaining LDL cholesterol. It has become the standard regardless of the cause of hypercholesterolemia because of its few side effects, its high tolerability, its ease of administration, its safety, and most of all because of its immense efficacy. This has not, however, prevented the exploration into other types of cholesterol therapies that may work in concurrence with statins. Drug classes such as PCSK9 inhibitors, ApoB inhibitors, MTP inhibitors, and thyromimetics have all been explored with varying success. Each of these potential therapies has a separate mechanism of action, allowing for modulation in conjunction with statins. PCSK9 inhibitors and ApoB inhibitors appear to provide the most upside by virtue of LDL lowering capabilities, followed by a drug known as ezetimibe that reduces dietary cholesterol uptake in the gut. MTP inhibitors have been shown to be effective therapies for homozygous familial hypercholesterolemia specifically due to their function of lowering LDL particle creation rather than LDL receptor number or function as statins and PCSK9 inhibitors do. Thyromimetics have yet to yield an effective therapy for cholesterol treatment, but the hope remains alive that this could come to fruition in the future

SUMMARY REPORT of a Faculty Colloquium Held on the Encyclical Letter Laudato Si’ of The Holy Father Francis on Care for Our Common Home

The Papal Encyclical, issued in summer of 2015, elicited the attention of ten faculty members in St. John’s College of Liberal Arts and Sciences. All but two of the participants were faculty members based primarily in Staten Island. What follows is a collection of highlights from the formal presentations

The JanDY Survey System

JanDY is a survey system built by students and faculty from Hope College’s Computer Science Department. It is the program that runs behind the scenes during the Student Assessment of Learning & Teaching surveys that all students take each semester, which are used by the institution and instructors to evaluate the effectiveness of all courses at Hope. The current system was built using the outdated Google Web Toolkit. Our goal was to build a new version of JanDY using a more modern web framework, AngularJS. Beyond updating the technologies used in the system, we also added new functionality, including an interface for the creation and editing of surveys. In order to ensure that our new system was reliable we constructed a comprehensive test suite in the development process, testing our web application and load handling with tools such as Mockito, Jasmine, Karma, and JMeter

Robust Optimization, Structure/Control co-design, Distributed Optimization, Monolithic Optimization, Robust Control, Parametric Uncertainty

This paper presents an end-to-end framework for robust structure/control optimization of an industrial benchmark. When dealing with space structures, a reduction of the spacecraft mass is paramount to minimize the mission cost and maximize the propellant availability. However, a lighter design comes with a bigger structural flexibility and the resulting impact on control performance. Two optimization architectures (distributed and monolithic) are proposed in order to face this issue. In particular the Linear Fractional Transformation (LFT) framework is exploited to formally set the two optimization problems by including parametric uncertainties. Large sets of uncertainties have to be indeed taken into account in spacecraft control design due to the impossibility to completely validate structural models in micro-gravity conditions with on-ground experiments and to the evolution of spacecraft dynamics during the mission (structure degradation and fuel consumption). In particular the Two-Input Two-Output Port (TITOP) multi-body approach is used to build the flexible dynamics in a minimal LFT form. The two proposed optimization algorithms are detailed and their performance are compared on an ESA future exploration mission, the ENVISION benchmark. With both approaches, an important reduction of the mass is obtained by coping with the mission's control performance/stability requirements and a large set of uncertainties

Studies on Dibenzylamines as Inhibitors of Venezuelan Equine Encephalitis Virus

Alphaviruses are arthropod-transmitted members of the Togaviridae family that can cause severe disease in humans, including debilitating arthralgia and severe neurological complications. Currently, there are no approved vaccines or antiviral therapies directed against the alphaviruses, and care is limited to treating disease symptoms. A phenotypic cell-based high-throughput screen was performed to identify small molecules that inhibit the replication of Venezuelan Equine Encephalitis Virus (VEEV). The compound, 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(3-fluoro-4-methoxybenzyl)ethan-1-amine (1), was identified as a highly active, potent inhibitor of VEEV with an effective concentration for 90% inhibition of virus (EC90) of 0.89 μM and 7.49 log reduction in virus titers at 10 μM concentration. These data suggest that further investigation of compound 1 as an antiviral therapeutic against VEEV, and perhaps other alphaviruses, is warranted. Experiments suggested that the antiviral activity of compound 1 is directed at an early step in the VEEV replication cycle by blocking viral RNA and protein synthesis

Affiliative behavior in Williams syndrome: Social perception and real-life social behavior

A frequently noted but largely anecdotal behavioral observation in Williams syndrome (WS) is an increased tendency to approach strangers, yet the basis for this behavior remains unknown. We examined the relationship between affect identification ability and affiliative behavior in participants with WS relative to a neurotypical comparison group. We quantified social behavior from self-judgments of approachability for faces, and from parent/other evaluations of real life. Relative to typical individuals, participants with WS were perceived as more sociable by others, exhibited perceptual deficits in affect identification, and judged faces of strangers as more approachable. In WS, high self-rated willingness to approach strangers was correlated with poor affect identification ability, suggesting that these two findings may be causally related. We suggest that the real-life hypersociability in WS may arise at least in part from abnormal perceptual processing of other people's faces, rather than from an overall bias at the level of behavior. While this did not achieve statistical significance, it provides preliminary evidence to suggest that impaired social-perceptual ability may play a role in increased approachability in WS

The New Keynesian business cycle achievements and challenges

The New-Keynesian (NK) business cycle model has presented itself as a potential “workhorse” model for business cycle analysis. This paper seeks to assess afresh the performance of the baseline NK model and its various extensions. The main theme of the paper is that although the dynamic NK literature has secured a robust defence to criticism arising, inter alia, on account of lack of microfoundations, it still has a long way to go in terms of providing a fully satisfactory model of the business cycle. In this regard, it is conjectured that explicitly accounting for the role of heterogeneity in business- cycle dynamics could lead towards a viable solution.info:eu-repo/semantics/publishedVersio

An open toolkit for tracking open science partnership implementation and impact.

Serious concerns about the way research is organized collectively are increasingly being raised. They include the escalating costs of research and lower research productivity, low public trust in researchers to report the truth, lack of diversity, poor community engagement, ethical concerns over research practices, and irreproducibility. Open science (OS) collaborations comprise of a set of practices including open access publication, open data sharing and the absence of restrictive intellectual property rights with which institutions, firms, governments and communities are experimenting in order to overcome these concerns. We gathered two groups of international representatives from a large variety of stakeholders to construct a toolkit to guide and facilitate data collection about OS and non-OS collaborations. Ultimately, the toolkit will be used to assess and study the impact of OS collaborations on research and innovation. The toolkit contains the following four elements: 1) an annual report form of quantitative data to be completed by OS partnership administrators; 2) a series of semi-structured interview guides of stakeholders; 3) a survey form of participants in OS collaborations; and 4) a set of other quantitative measures best collected by other organizations, such as research foundations and governmental or intergovernmental agencies. We opened our toolkit to community comment and input. We present the resulting toolkit for use by government and philanthropic grantors, institutions, researchers and community organizations with the aim of measuring the implementation and impact of OS partnership across these organizations. We invite these and other stakeholders to not only measure, but to share the resulting data so that social scientists and policy makers can analyse the data across projects

Costly Information, Planning Complementarities and the Phillips Curve

Standard sticky information pricing models successfully capture the sluggish movement of aggregate prices in response to monetary policy shocks but fail at matching the magnitude and frequency of price changes at the micro level. This paper shows that in a setting where firms choose when to acquire costly information about different types of shocks, strategic complementarities in pricing generate planning complementarities. This results in firms optimally updating their information about monetary policy shocks less frequently than about idiosyncratic shocks. When calibrated to match frequent and large price changes observed in micro pricing data, the model is still capable of producing substantial non-neutralities. In addition, I use the model consistent Phillips curve and data from the Survey of Professional Forecasters to estimate the frequency at which firms update their information about monetary policy shocks. I find that the frequency of updating was higher in the 1970s compared to subsequent decades and hence conclude that monetary policy in the U.S. was relatively less effective prior to the 1980s