Testing and Developing DIY Masks

ME450 Capstone Design and Manufacturing Experience: Fall 2020The purpose of this design project is to develop a DIY mask to combat the shortage of N95 respirators and medical masks in low resource settings. In the preliminary stages of the project, meetings with stakeholders, mostly in the form of experts in the area of study, were conducted. Research was also done on literature in the area, which led to the development of engineering specifications. The mask should have a low cost of fewer than 2 cedis or 0.34 USD. The mask should be made in less than 30 minutes with fewer than 12 steps of instructions. The mask should filter over 50% of particles over 50 nm in size. The mask should fit well to the face and minimize airflow around the edge with a fit factor greater than or equal to 2. The mask should also be comfortable to wear with average scores greater than 4 on a 6 point Likert scale. Finally, the mask should sustain a long lifespan, supporting over 20 uses with a decontamination cycle in between each use. Using a combination of design heuristics and a morphological matrix, several designs were brainstormed to meet the project requirements. These designs were then filtered using a decision matrix, resulting in the three best designs. Engineering analyses were then developed to further evaluate the mask designs and answer some key design drivers. The first and simplest test was the Mask Fabrication Test, which simply recorded the time it took to create the masks. The test indicated that the three designs had a comparable fabrication time. The next substantial test that was conducted was the Mask Fit Test, which measured airflow around the masks. From this test, various factors of the best performing masks were determined. To help ensure the mask was comfortable, several steps were taken. First, a Comfort Priority Survey was conducted, which helped provide context for the results of the Mask Comfort Test. Then, prototypes of the three mask designs were tried on and rated for various aspects of comfort by people close to team members. From these tests, the nylon design was chosen as the final design, with a few modifications. The final design uses three layers of material -cotton, silk, and nylon- to filter out particles. The nylon layer also acts as the ear straps for comfortability. Wires are sewn inside the top and bottom of the mask to improve fit, and pleats are sewn on the side for flexibility. One final comfort test was conducted with the design, which verified the requirement. The low-cost requirement was verified through calculations, and the “uses available materials requirement” was verified from research. The “is easy to create” requirement was verified with a use test. To verify the lifetime and filtration efficiency requirements, a Mask Filtration Efficiency Test was performed. However, due to a lack of testing time, no conclusive results were obtained from the test, and the lifetime and filtration efficiency requirements were left unverified. An inability to test also left the fit requirement unverified. By the end of the project, a design and instructions on creating the design were created. This design has been verified to fulfill 4 out of 7 requirements. The filtration efficiency, lifetime, and fit requirements all require further testing for verification.Caroline Soyars, U-M Mechanical Engineeringhttp://deepblue.lib.umich.edu/bitstream/2027.42/164436/1/Testing_and_Developing_DIY_Masks.pd

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

ObjectiveRecent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial.MethodsThe Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable.ResultsOf 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20).ConclusionAmong older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Development of a Standardized Benchmark Assessment Tool to Facilitate EBP for Students with ASD

The purpose of this paper is to describe the development of an accessible, standardized benchmark assessment (i.e., the Evidence Based Practice Classroom Checklist (EBP CC)) to support administrators, school leaders, and educators in collaborative implementation of evidence-based practices for students with autism spectrum disorder (ASD). This series of studies occurred in three phases across two states. The first phase was design and content validity testing. The second phase was testing of the implementation process in schools including reliability assessments. Finally, the third phase addressed implementation on a larger scale and evaluation. Results indicated the EBP CC was a valid tool that represented the foundational practices necessary for students with ASD. Administrators found such a tool important and necessary. Additionally, results indicated reliability in measuring evidence based practices used in classrooms. Implications for research and practice are discussed

A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements

This study determined if twice-daily consumption of a nutrient-dense bar intended to fill gaps in Western diets, without other dietary/lifestyle requirements, favorably shifted metabolic/anthropometric indicators of dysregulation in a healthy direction. Three 8-wk clinical trials in 43 healthy lean and overweight/obese (OW/OB) adults, who served as their own controls, were pooled for analysis. In less inflamed OW/OB [highsensitivity C-reactive protein (hsCRP) \u3c1.5], statistically significant decreases occurred in weight (-1.1 ± 0.5 kg), waist circumference (-3.1 ± 1.4 cm), diastolic blood pressure (-4.1 ± 1.6 mmHg), heart rate [HR;-4.0 ± 1.7 beats per minute (bpm)], triglycerides (272638.2mg/dl), insulin resistance (homeostatic model of insulin resistance) (-0.72 ± 0.3), and insulin (-2.8 ± 1.3 mU/L); an increase in HDL-2b (+303 ± 116 nM) and realignment of LDL lipid subfractions toward a less atherogenic profile [decreased small LDL IIIb (-44 ± 23.5 nM), LDL IIIa (299643.7nM),andincreased largeLDLI (+66±28.0nM)]. In the more inflamed OW/OB (hsCRP \u3e1.5), inflammation was reduced at 2 wk (20.66 mg/L), and HR at 8 wk (-3.4 ± 1.3 bpm). The large HDL subfraction (10.5–14.5 nm) increased at 8 wk (+346 ± 126 nM). Metabolic improvements were also observed in lean participants. Thus, favorable changes in measures of cardiovascular health, insulin resistance, inflammation, and obesity were initiated within 8 wk in the OW/OB by replacing deficiencies in Western diets without requiring other dietary or lifestyle modifications; chronic inflammation blunted most improvements.—McCann, J. C., Shigenaga, M. K., Mietus-Snyder, M. L., Lal, A., Suh, J. H., Krauss, R. M., Gildengorin, G. L., Goldrich, A. M., Block, D. S., Shenvi, S. V.,McHugh, T. H.,Olson,D. A., Ames, B.N. A multicomponent nutrient bar promotes weight loss and improves dyslipidemia and insulin resistance in the overweight/obese: chronic inflammation blunts these improvements

Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials

BackgroundLimited information is available on the performance characteristics of 2 questionnaires commonly used in clinical research, the Psychosexual Daily Questionnaire (PDQ) and the Derogatis Interview for Sexual Function (DISF)-II Assessment, especially in older men with low testosterone (T) and impaired sexual function.AimTo determine reliability of PDQ and DISF-II by assessing the correlation within and between domains in the questionnaires and to define clinically meaningful changes in sexual activity (PDQ question 4 [Q4]) and desire (DISF-II sexual desire domain [SDD]) domains.MethodsData from 470 men participating in the T Trials were used to calculate Spearman correlation coefficients of individual items and total score among questionnaires to determine convergent and construct validity. Clinically meaningful changes for sexual desire and activity were determined by randomly dividing the sample into training and validation sets. Anchor- and distribution-based clinically meaningful change criteria were defined in the training set, and selected changes were evaluated in the validation set.OutcomesValidity of the PDQ and DISF-II and clinically meaningful changes in sexual desire and activity were determined in older men in T Trials.ResultsModerate to strong correlations were shown within and between domains from different questionnaires. Using Patient Global Impression of Change as an anchor, clinically meaningful change in PDQ sexual activity was ≥0.6, and in DISF-SDD was ≥5.0. Applying these change cut-points to the validation set, a greater proportion of T-treated men achieved clinically meaningful improvement in their sexual desire and activity compared to placebo-treated men.Clinical implicationsThe PDQ-Q4 and DISF-II-SDD can be used to reliably assess clinically meaningful changes in sexual activity and sexual desire in hypogonadal men treated with T.Strengths & limitationsStrengths of this study include a large sample size, long trial duration, and inclusion of men with low libido and unequivocally low T levels. Limitations include using data from a single study that enrolled only older hypogonadal men, and only 1 anchor for both sexual desire and activity.ConclusionModerate to strong correlations were demonstrated within and between different sexual domains of the PDQ and DISF-II confirming construct and convergent validity. Clinically meaningful improvement in elderly hypogonadal men was change of ≥0.6 score in the PDQ-Q4 and ≥5.0 in the DISF-SDD. Improvements in sexual activity and desire in the T Trials were modest but clinically meaningful. Wang C, Stephens-Shields AJ, DeRogatis LR, et al. Validity and Clinically Meaningful Changes in the Psychosexual Daily Questionnaire and Derogatis Interview for Sexual Function Assessment: Results From the Testosterone Trials. J Sex Med 2018;15:997-1009