Bringing People Back into Public Health Data: Community Feedback on a Set of Visualization Tools - Summary Report

This course-based study is a product of the University of Denver’s Spring 2022 The Social Determination of Health (ANTH 2424) class. The study aimed to understand how well a set of public health visualization tools tells the data stories about people in Colorado, and about important public health problems. For this, a team of almost sixty undergraduate students taking the class, coordinated by three graduate teaching assistants, and directed by the course instructor interviewed a total of fifty-six people from Colorado, qualitatively analyzed those interviews, and wrote reports that draw conclusions and recommendations

The effects of direct current stimulation on exercise performance, pacing and perception in temperate and hot environments

Background. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique and has previously been shown to enhance submaximal exercise by reducing rating of perceived exertion (RPE). The present study examined the effects of tDCS on high-intensity self-paced exercise in temperate conditions and fixed followed by maximal exercise in the heat; it was hypothesised performance and RPE would be altered. Methods. Two separate studies were undertaken in which exercise was preceded by 20-minutes of sham tDCS (SHAM), or anodal tDCS (TDCS). Study 1: six males completed a 20-km cycling time trial, on two occasions. Power output (PO), RPE, O2 pulse, and heart rate (HR) were measured throughout. Study 2: eight males completed fixed intensity cycling exercise at 55% of a pre-determined maximal power output (PMax) for 25-minutes before undertaking a time to exhaustion test (TTE; 75% PMax) in hot conditions (33°C), on two occasions. Test duration, heart rate, thermal and perceptual responses were measured. Study specific and combined statistical analyses was undertaken and effect sizes established.. Results. Study 1: mean PO was not improved with the tDCS (197 ± 20 W) compared to SHAM (197 ± 12 W) and there were no differences in pacing profile HR, O2 pulse or RPE (p > .05). Study 2: TTE duration (SHAM 314 ± 334 s cf 237 ± 362 s tDCS), thermal, heart rate and perceptual responses were unchanged by tDCS compared to SHAM (p > .05). When combined, performance in the SHAM trial tended to better than the tDCS. Conclusion. tDCS did not influence cycling performance (study 1) exercise tolerance (study 2) or perception (studies 1&2). tDCS does not appear to facilitate high intensity exercise performance or exercise performance in the heat

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Biomarkers of systemic treatment response in people with psoriasis: a scoping review

Background Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. Objectives To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community. Methods A systematic search of CENTRAL, Embase, LILACS, and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving the psoriasis population (any age, n≥50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data was extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multi-stakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways. Results Of 71 included studies (n=64 effectiveness outcomes and n=8 safety outcomes), most reported genomic or proteomic biomarkers associated with response to biologics (n=48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key prognostic factors, lack of adjustment for multiple testing and selective outcome reporting. We identified candidate biomarkers of efficacy to TNF inhibitors (variation in CARD14, CDKAL1, IL1B, IL12B, IL17RA loci and LPS-induced phosphorylation of NF-kB in Type 2 dendritic cells) and ustekinumab (HLA-C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, Th17 cell differentiation, positive regulation of NF-kB and Th17 cell activation. Conclusions This comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. Candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use

Biomarkers of disease progression in people with psoriasis: a scoping review

peer reviewed[en] BACKGROUND: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice. OBJECTIVES: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community. METHODS: A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways. RESULTS: Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation. CONCLUSIONS: This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area

X-ray-induced photo-chemistry and X-ray absorption spectroscopy of biological samples

As synchrotron light sources and optics deliver greater photon flux on samples, X-ray-induced photo-chemistry is increasingly encountered in X-ray absorption spectroscopy (XAS) experiments. The resulting problems are particularly pronounced for biological XAS experiments. This is because biological samples are very often quite dilute and therefore require signal averaging to achieve adequate signal-to-noise ratios, with correspondingly greater exposures to the X-ray beam. This paper reviews the origins of photo-reduction and photo-oxidation, the impact that they can have on active site structure, and the methods that can be used to provide relief from X-ray-induced photo-chemical artifacts. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved

Highly parallel genome variant engineering with CRISPR–Cas9

Understanding the functional effects of DNA sequence variants is of critical importance for studies of basic biology, evolution, and medical genetics; however, measuring these effects in a high-throughput manner is a major challenge. One promising avenue is precise editing with the CRISPR-Cas9 system, which allows for generation of DNA double-strand breaks (DSBs) at genomic sites matching the targeting sequence of a guide RNA (gRNA). Recent studies have used CRISPR libraries to generate many frameshift mutations genome wide through faulty repair of CRISPR-directed breaks by nonhomologous end joining (NHEJ) 1 . Here, we developed a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. We used our method to examine the functional consequences of premature-termination codons (PTCs) at different locations within all annotated essential genes in yeast. We found that most PTCs were highly deleterious unless they occurred close to the 3' end of the gene and did not affect an annotated protein domain. Unexpectedly, we discovered that some putatively essential genes are dispensable, whereas others have large dispensable regions. This approach can be used to profile the effects of large classes of variants in a high-throughput manner