Reliable and accurate diagnostics from highly multiplexed sequencing assays

Scalable, inexpensive, and secure testing for SARS-CoV-2 infection is crucial for control of the novel coronavirus pandemic. Recently developed highly multiplexed sequencing assays (HMSAs) that rely on high-throughput sequencing can, in principle, meet these demands, and present promising alternatives to currently used RT-qPCR-based tests. However, reliable analysis, interpretation, and clinical use of HMSAs requires overcoming several computational, statistical and engineering challenges. Using recently acquired experimental data, we present and validate a computational workflow based on kallisto and bustools, that utilizes robust statistical methods and fast, memory efficient algorithms, to quickly, accurately and reliably process high-throughput sequencing data. We show that our workflow is effective at processing data from all recently proposed SARS-CoV-2 sequencing based diagnostic tests, and is generally applicable to any diagnostic HMSA

The Concept of Hope in Social Work Practice and Education

The concept of hope has been and continues to be part of the research literature in many human service fields, such as medicine, psychology and nursing. The research on hope in these fields has shown that its presence can have multiple benefits for persons in differing forms of distress. However, any discussion on hope has been conspicuously absent from most social work literature for almost forty years. This qualitative study has been designed to begin a begin a discussion on the role of hope in social work practice and education. Seven social workers were interviewed on their understanding of hope, whether and how they integrate hope into their practice, and whether they believe hope should be studied more. The results indicate that social workers do believe hope to be an important concept in their work and that they are attempting to integrate it into their practice. However, they suspect that the social work profession does not share or support their values in this area

The miscalibration of the honeybee odometer

We examine a series of articles on honeybee odometry and navigation published between 1996 and 2010, and find inconsistencies in results, duplicated figures, indications of data manipulation, and incorrect calculations. This suggests that redoing the experiments in question is warranted.Comment: 16 page

Study of Alpha-Sigma Phase Transformation in Mechanically Alloyed Fe-Cr-Sn Alloys

The solubility of tin is significantly extended by mechanical alloying in near equiatomic Fe-Cr alloys. The influences of Sn concentration and of grain size on the kinetics of formation of the sigma-phase have been studied using different techniques. The sigma-phase formation is much faster for as-milled alloys than it is for conventional alloys. The sigma-phase formation rate decreases with the increase of Sn concentration in alloys with nanometer-sized grains as it does in coarse-grained alloys. The mechanisms which are responsible for the slowing-down of the alpha-sigma transformation are different in both kinds of alloys

Measuring Standard of Care Physical Parameters in an Academic Psychiatric Practice During the COVID Pandemic – a Trainee Driven Quality Improvement Study

Background Outpatient Psychiatric services need to monitor certain evidence-based quality indicators that promote patient safety and guide standards of care. Our Child and Adolescent Psychiatry (CAP) fellow outpatient clinic provides psychotherapy and pharmacological management to a population in a major metropolitan city, who belong to various minority predominantly African American and reduced socio-economic at-risk groups. The COVID pandemic has brought about a lot of changes in psychiatric practice which includes Telepsychiatry. This study aims to determine if greater use of telepsychiatry has resulted in changes in compliance with the evaluation of basic vital sign parameters of our patients during the peripandemic era

In-silico screening of lipid-based drug delivery systems

Purpose: This work proposes an in-silico screening method for identifying promising formulation candidates in complex lipid-based drug delivery systems (LBDDS). Method: The approach is based on a minimum amount of experimental data for API solubilites in single excipients. Intermolecular interactions between APIs and excipients as well as between different excipients were accounted for by the Perturbed-Chain Statistical Associating Fluid Theory. The approach was applied to the in-silico screening of lipid-based formulations for ten model APIs (fenofibrate, ibuprofen, praziquantel, carbamazepine, cinnarizine, felodipine, naproxen, indomethacin, griseofulvin and glibenclamide) in mixtures of up to three out of nine excipients (tricaprylin, Capmul MCM, caprylic acid, Capryol™ 90, Lauroglycol™ FCC, Kolliphor TPGS, polyethylene glycol, carbitol and ethanol). Results: For eight out of the ten investigated model APIs, the solubilities in the final formulations could be enhanced by up to 100 times compared to the solubility in pure tricaprylin. Fenofibrate, ibuprofen, praziquantel, carbamazepine are recommended as type I formulations, whereas cinnarizine and felodipine showed a distinctive solubility gain in type II formulations. Increased solubility was found for naproxen and indomethacin in type IIIb and type IV formulations. The solubility of griseofulvin and glibenclamide could be slightly enhanced in type IIIb formulations. The experimental validation agreed very well with the screening results. Conclusion: The API solubility individually depends on the choice of excipients. The proposed in-silico-screening approach allows formulators to quickly determine most-appropriate types of lipid-based formulations for a given API with low experimental effort

Parkin loss of function contributes to RTP801 elevation and neurodegeneration in Parkinson"s disease

Mutations in the PARK2 gene are associated with an autosomal recessive form of juvenile parkinsonism (AR-JP). These mutations affect parkin solubility and impair its E3 ligase activity, leading to a toxic accumulation of proteins within susceptible neurons that results in a slow but progressive neuronal degeneration and cell death. Here, we report that RTP801/REDD1, a pro-apoptotic negative regulator of survival kinases mTOR and Akt, is one of such parkin substrates. We observed that parkin knockdown elevated RTP801 in sympathetic neurons and neuronal PC12 cells, whereas ectopic parkin enhanced RTP801 poly-ubiquitination and proteasomal degradation. In parkin knockout mouse brains and in human fibroblasts from AR-JP patients with parkin mutations, RTP801 levels were elevated. Moreover, in human postmortem PD brains with mutated parkin, nigral neurons were highly positive for RTP801. Further consistent with the idea that RTP801 is a substrate for parkin, the two endogenous proteins interacted in reciprocal co-immunoprecipitates of cell lysates. A potential physiological role for parkin-mediated RTP801 degradation is indicated by observations that parkin protects neuronal cells from death caused by RTP801 overexpression by mediating its degradation, whereas parkin knockdown exacerbates such death. Similarly, parkin knockdown enhanced RTP801 induction in neuronal cells exposed to the Parkinson's disease mimetic 6-hydroxydopamine and increased sensitivity to this toxin. This response to parkin loss of function appeared to be mediated by RTP801 as it was abolished by RTP801 knockdown. Taken together these results indicate that RTP801 is a novel parkin substrate that may contribute to neurodegeneration caused by loss of parkin expression or activity