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Volatile radioisotopes represent a substantial health risk when released into the environment. To better understand the environmental fate of radioisotopes, the authors constructed a cylindrical steel-walled chamber to simulate the atmospheric processing of volatile radioactive gases. Optical modeling was performed for the properties of simulated sunlight in the chamber to better characterize atmospheric reaction studies. Optical simulations were performed using two wall materials (steel and thin-film silica) and validated against experimental measurements. This optical analysis methodology can be used to improve the fidelity of atmospheric models by accounting for optical inhomogeneities enabling a firmer grasp of radioisotopes’ environmental fate. Graphical abstract

Vaccination with JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to prevent monkeypox commenced shortly after confirmation of the first monkeypox case in the current outbreak in the United States on May 17, 2022 (1). To date, more than 27,000 cases have been reported across all 50 states, the District of Columbia (DC), and Puerto Rico.* JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3). The U.S. Department of Health and Human Services (HHS) allocated 1.1 million vials of JYNNEOS vaccine from the Strategic National Stockpile, with doses allocated to jurisdictions based on case counts and estimated size of population at risk (4). However, initial vaccine supplies were severely constrained relative to vaccine demand during the expanding outbreak. Some jurisdictions with highest incidence responded by prioritizing first dose administration during May-July (5,6). The FDA emergency use authorization (EUA) of 0.1 mL dosing for intradermal administration of JYNNEOS for persons aged ≥18 years on August 9, 2022, substantially expanded available vaccine supply

The purpose of this study was to compare the effectiveness of the only Food and Drug Administration-authorized prescription digital therapeutic (PDT) Somryst versus face-to-face cognitive behavioral therapy for insomnia (CBT-I), or FDA-approved prescription medications for insomnia.A systematic literature review was undertaken to identify relevant studies. A Bayesian network meta-analysis (NMA) was conducted to examine (1) mean change in insomnia severity index (ISI); (2) proportional change in ISI remitters; (3) mean change in wake after sleep onset (WASO); and (4) mean change in sleep onset latency (SOL).Twenty studies provided data on the PDT, CBT-I, CBT-I in combination with self-help (SH), or two prescription medications (eszopiclone and zolpidem). The PDT was associated with significant mean change in ISI (-5.77, 95% Credible Interval [CrI] - 8.53, -3.07) and ISI remitters (OR 12.33; 95% CrI 2.28, 155.91) compared to placebo, and had the highest probability of being the most effective treatment overall for ISI mean change (56%), and ISI remitters (64%). All evaluated interventions significantly outperformed placebo for WASO but no significant differences were observed for SOL (five interventions). Sensitivity analyses excluding medications and meta-regression (assessing type, duration, delivery method for CBT-I) did not affect NMA results.This network meta-analysis demonstrated that a PDT delivering CBT-I had the highest probability of being most effective compared to face-to-face CBT-I, prescription sleep medications, or placebo, as measured by reductions in mean ISI score from baseline and ISI-determined remittance.Chronic insomnia is the long-term inability to fall asleep easily or to stay asleep. This condition is much more serious than most people realize, raising the risk of many health problems including depression, heart disease, and injuries.Although sleep medications are commonly used to treat insomnia, these drugs may not be effective and can lead to harms such as accidents or clouded thinking. Clinical guidelines recommend a treatment called cognitive behavioral therapy for insomnia (CBT-I) that is safe and effective. Unfortunately, there is a shortage of clinicians trained to provide CBT-I.Prescription digital therapeutics (PDTs) are FDA-approved software programs available on mobile devices such as smartphones. A PDT for insomnia (Somryst) delivers CBT-I and can overcome barriers to access for this important type of therapy. To compare the effectiveness of this PDT with FDA-approved sleep medications and face-to-face CBT-I a special kind of study was conducted called a network meta-analysis. This is a statistical method of combining data from numerous studies in a way that allows the results to be fairly compared.This network meta-analysis of 20 studies found that the PDT was more effective at reducing insomnia symptoms than any of the sleep medications studied and was even more effective than face-to-face CBT-I as measured by scores on a clinically valid scale of insomnia symptoms. These results are encouraging because they suggest that digital delivery of CBT-I could help the millions of people who currently do not have access to this effective treatment.

With the developments of Industry 4.0, data analytics solutions and their applications have become more prevalent in the manufacturing industry. Currently, the typical software architecture supporting these solutions is modular, using separate software for data collection, storage, analytics, and visualization. The integration and maintenance of such a solution requires the expertise of an information technology team, making implementation more challenging for small manufacturing enterprises. To allow small manufacturing enterprises to feasibly obtain the benefits of Industry 4.0 data analytics, a full-stack data analytics framework is presented, and its performance evaluated as applied in the common industrial analytics scenario of predictive maintenance. The predictive maintenance approach was achieved by using a full-stack data analytics framework comprised of the PTC Inc. Thingworx software suite. When deployed on a lab-scale factory, there was a significant increase in factory uptime in comparison with both preventive and reactive maintenance approaches. The predictive maintenance approach simultaneously eliminated unexpected breakdowns and extended the uptime periods of the lab-scale factory. This research concluded that similar or better results may be obtained in actual factory settings, since the only source of error on predictions in the testing scenario would not be present in real world scenarios. An analysis of the effect of downtime period durations and discussion on the cost of reactive maintenance and associated breakdowns is also presented.

During the COVID-19 pandemic, media accounts emerged describing faith-based organizations (FBOs) working alongside health departments to support the COVID-19 response. In May 2021, the Department of Health and Human Services, Centers for Disease Control and Prevention, and the Association of State and Territorial Health Officials (ASTHO) sent an electronic survey to the 59 ASTHO member jurisdictions and four major US cities to assess state and territorial engagement with FBOs. Findings suggest that public health officials in many jurisdictions were able to work effectively with FBOs during the COVID-19 pandemic to provide essential education and mitigation tools to diverse communities. (Am J Public Health. 2022;112(3):397–400. https://doi.org/10.2105/AJPH.2021.306620 )

Tracking mass through harsh environments requires surrogate particles that withstand the event and endure until sampling. Silica-covered quantum dots have been shown to withstand a range of environmental pHs from months to years; in this work they are shown to endure in anticipated local environments. Two methods of particle synthesis were employed to produce luminescent silica with particle diameters 0.1–4 μm. These tracer particles scale for mass production, tolerate harsh environments, and endure in debris. They could be deployed in places such as chemical explosions, industrial processes, geologic test beds, oil and gas fields, nuclear reactors, and geothermal plants to track mass under harsh conditions. Graphical abstract

Background: Given a hepatitis C virus (HCV) elimination goal by 2030, World Health Organization (WHO) guidelines recommend scaling up HCV screening and treatment with highly-effective direct-acting antivirals (DAAs). This study investigated the cost-effectiveness of various screening and treatment strategies for chronic HCV patients in South Korea in patients aged over 40 as compared to currently screening only high-risk patients. Methods: A published Markov disease progression model was used with a screening/treatment decision-tree to model different screening and treatment strategies for Korean HCV patients (aged over 40) from a national payer perspective over a lifetime time horizon. The screening strategies included ���screen-all��� (upfront only: ���once���; or upfront and age 65: ���twice���) or a ���high-risk only��� screening strategy followed by treatment. Treatment strategies included either ledipasvir/sofosbuvir (LDV/SOF), SOF + ribavirin (SOF + RBV; in GT2 only), or glecaprevir/pibrentasvir (GLE/PIB). Model inputs were sourced from published literature and costing databases and validated by Korean hepatologists. Results: Regardless of treatment strategy, a ���screen all twice��� scenario led to the lowest rates of advanced liver disease events compared to ���screen all once��� and ���high-risk only��� screening scenarios. In this screening scenario, treatment with LDV/SOF for GT1/2 dominates (i.e., is more effective and less4costly) LDV/SOF in GT1 and SOF + RBV in GT2, while GLE/PIB is not cost-effective relative to LDV/SOF (���105,124,920/QALY) at a willingness-to-pay threshold of 1xGDP per capita. Conclusion: Screening all South Korean patients twice followed by LDV/SOF treatment is cost-effective as compared current high-risk screening. Adopting this strategy can help achieve WHO HCV elimination goals.

From cryptic ciphers and wall-climbing robots to dinosaur digs and visits to the planetarium, this year's finalists for the Science Books and Films (SB&F) Prizes for Excellence in Science Books are packed with fun facts, easy-to-do experiments, and plenty of creepy-crawly creatures. Sponsored by Subaru and the American Association for the Advancement of Science (AAAS, the publisher of Science ), the SB&F competition celebrates high-quality science books for young readers. Read on for reviews of the finalists, written by the staff of the Science family of journals, with help from a few friends.

Objective This study aimed to understand the impact of different efficacy endpoints on reimbursement decisions made by health technology assessment (HTA) bodies. Materials and methods European Medicines Agency (EMA) oncology product marketing authorizations were screened to identify products that completed review by 3 HTA bodies during 2016-2019: United Kingdom's National Institute for Health and Care Excellence, Germany's Gemeinsamer Bundesausschuss, and France's Haute Autorite de Sante. Each decision's endpoint information, including overall survival (OS) and progression-free survival (PFS), was extracted. Each endpoint's influence on added benefits rating (the degree of added benefit as judged by the HTA agency) and full reimbursement (ie, reimbursed population to label) decisions was tested using bivariate analyses. Results An increasing trend was observed toward HTA submissions with immature OS data (36.8% and 71.4% in 2016 and 2019, respectively), which was a predictor of limited added benefit (P .05) decisions, whereas PFS without OS had no significant impact compared with either OS or PFS data for either outcome (P=.99). Conclusions The trend toward fewer products filing mature OS data over time suggests sponsors may be increasingly confident achieving reimbursement with surrogate endpoint data, although mature OS data provided the strongest correlation to positive reimbursement decisions. Notably, in some locally advanced settings, OS data maturity will take a long time to obtain. To expedite patient access to new medicines, payers should consider acceptance of surrogate endpoints predictive of clinical benefit.

Introduction Limitations on the availability of guideline-recommended cognitive behavioral therapy for insomnia (CBT-I) constrain its use and create an unmet need for innovative ways to expand access. Digital therapeutics offer a potential solution. This study compared a digital intervention, traditional face-to-face CBT-I, and prescription medications for insomnia. Methods Of 184 articles identified in a systematic literature review, 13 studies reported ISI mean change from baseline data: 1 using the digital therapeutic (DT) SHUTi (now known as the prescription digital therapeutic Somryst), 1 on the medication eszopiclone, and 11 on traditional CBT. A Bayesian network meta-analysis (NMA) was performed on the mean change from baseline and the proportion of remitters using the insomnia severity index (ISI) endpoint with follow-up timepoints between 6-12 weeks. Mean change in ISI score from baseline was analyzed as a continuous endpoint while comparisons of the proportion of remitters was performed using odds ratios. The analysis used a random-effects model for the base case analysis. A surface under the cumulative ranking curve (SUCRA) analysis was performed to rank the treatments on each endpoint. Results Only the DT and CBT-I were significantly different than placebo. The DT had the greatest mean change from baseline in ISI from placebo (-5.77 points, 95% Credible Interval (CrI) [-8.53, -3.07]), followed by CBT-I (-4.3 points, 95% CrI [-6.32, -2.39]). In the SUCRA analysis, the DT had the highest probability (56%) of being the most effective treatment based on ISI mean change from baseline. 8 studies reported the proportion of ISI remitters. Only the DT showed a statistically significant difference in remission vs. placebo, and the DT had the highest odds ratio for remission vs. placebo (OR 12.33; 95%CrI [2.28, 155.91]). The DT had the highest probability (64%), of being the most effective treatment for inducing remission using ISI definitions. Conclusion The DT in this study was projected to be the most effective therapy on both mean change in ISI and ISI remission within 6-12 weeks of treatment start vs. either traditional CBT-I or medications. Support (If Any) This analysis was funded by Pear Therapeutics, Inc.

What can a lowly lichen reveal about a grisly murder case? Which common clothing item requires 5000 gallons of water to create? Where is the best place for a pilot to crash a malfunctioning airplane? Chockful of interesting trivia and thoughtful scholarship, the books on this year's fall reading list—reviewed by alumni of the AAAS Science and Technology Policy Fellowship program—tackle topics ranging from the future of food to the nature of reality. Consider a careful analysis of why we ought to trust science or join a harrowing expedition to the most extreme environments on Earth. Dive into a fascinating quest to identify new elements or crack open an eye-opening history of color science.

Sodium-ion batteries are potential alternatives to lithium-ion batteries due to the natural abundance, and relatively low cost, of sodium. When used as a Na-ion battery cathode material, P2-type Na0.67Mn0.65Fe0.35O2 (NMFO) displays high reversible capacity (185 mAhg−1) and undergoes structural transitions between P63/mmc, P63 (OP4) and orthorhombic Cmcm during charge-discharge cycling between 1.5 and 4.3 V. Using Rietveld crystal structure refinement, we report that these structural transitions are completely suppressed in Na0.67Mn0.625Fe0.25Ni0.125O2 (NMFNO) during cycling. Interestingly, during discharge to 1.5 V, a mixture of two separate P63/mmc phases appears. Reversible capacity and specific energy of NMFNO are superior up to 100 cycles in the 1.5–4.0 V range, and to at least 200 cycles for 2.0–4.0 V. NMFNO displays first-cycle specific energy of 335 Whg−1, compared with 275 Whg−1 for NMFO. Scanning Electron Microscopy of the cathode surfaces after 200 cycles reveals performance-eroding cracks, and a solid electrolyte interface (SEI). Electrochemical Impedance Spectroscopy (EIS) shows that the total impedance of NMFNO between 1000 kHz and 0.1 Hz is significantly lower than NMFO after 200 cycles. We conclude that Ni substitution stabilizes the crystal structure by suppressing structural transitions in NMFO during cycling.

Several real-time Energy Visualization (EV) systems have emerged in the market in recent years with specific applications for large industrial and commercial facilities and residential buildings. However, light commercial businesses have been neglected with only a few attempts for EV solutions. In this study a framework for an economical, flexible, and plug and play EV system for the light commercial businesses is presented. It was hypothesized that the proposed framework will provide flexible yet cost effective energy efficiency solutions. Our specific contributions are (1) critical evaluation of existing EV systems, (2) development of framework with respect to operational, technical and budgetary challenges that are specific to light commercial businesses, (3) a computerized program to guide business owners through a step-by-step process involved in the development and installation of the EV system. To test the hypothesis, a field study was conducted by performing energy audits at 15 light commercial businesses. On average, the cost of the EV system was found to be 5% of the annual energy cost. Overall, the findings from our field study conclude that the proposed EV system is economical and flexible enough to address “varied and unique” energy efficiency requirements of light commercial businesses.

Given the goal of hepatitis C virus elimination by 2030, World Health Organization guidelines recommend treatment of chronic hepatitis C (CHC) with pan-genotypic direct-acting antivirals, such as sofosbuvir/velpatasvir (SOF/VEL), SOF/VEL/voxilaprevir (VOX) or glecaprevir/pibrentasvir (GLE/PIB). The study evaluated the cost-effectiveness of pan-genotypic regimens in initial (SOF/VEL or GLE/PIB) and re-treatment (SOF/VEL/VOX or GLE/PIB+SOF+ribavirin (RBV)) of CHC.A Markov state-transition model projected lifetime CHC health and economic outcomes from the US payer perspective. Model inputs were sourced from clinical trials or published literature and validated by hepatologists. Model outcomes included numbers of advanced liver disease events, life-years and quality-adjusted life-years (QALYs) gained, and total lifetime costs. One-way sensitivity analyses were performed on model results.SOF/VEL followed by SOF/VEL/VOX resulted in comparable cure rates to the GLE/PIB treatment pathway (99.94% vs. 99.93%, respectively). SOF-based regimens provided similar QALYs at a lower lifetime cost versus a GLE/PIB treatment pathway ($30,749 vs. $36,255), resulting in cost savings of $5,506 per patient. Results were robust in sensitivity analyses.SOF/VEL followed by SOF/VEL/VOX leads to comparable cure rates in the overall CHC population relative to the GLE/PIB treatment pathway. Based on wholesale acquisition prices, the SOF/VEL treatment pathway led to lower lifetime costs.

Background: The prevalence of blood-borne pathogens, including HIV and hepatitis B and C, remains high in sub-Saharan Africa. Nurses and midwives are therefore at high risk for occupational transmission. Aims: To examine the prevalence of sharps injuries and other work-related risks among nurses and midwives. Methods: Nurses and midwives (n=712) in sub-Saharan Africa completed an anonymous questionnaire. Generalised estimating questions were used to analyse the data. Findings: Nurses and midwives who made home visits, engaged in direct care, were called in to work ‘off-hours’, and performed needle-related tasks ≥15 times/day were more likely to have sharps injuries (all PConclusions: Future efforts should focus on optimising work schedules, reducing unnecessary needle-related tasks, introducing safety engineered needles and improving post-exposure prophylaxis.

Modern more electric aircraft (MEA) are increasingly reliant on robust power generation systems to drive basic aircraft systems, such as propulsion and control surface actuation, among others. These MEA loads require a low impedance and high bandwidth generator source. In turn, generation capacity and capability increases, and with it, the available current in the event of an arc fault. Such a fault may result in a catastrophic release of energy and the potential loss or extensive damage to the aircraft. In this paper, parallel arc faults for a type of aircraft generator are simulated, and a new mitigation method is introduced. This novel method makes use of available generator feedback control structures to greatly reduce the duration of the arc fault, thereby minimizing fault energy. The method is compared via computer simulations to two other feasible methods, one that turns off the generator's exciter and one that opens the exciter circuit. Further, since fault detection is not instantaneous, the paper also investigates the consequences of delay in fault detection by numerically evaluating the amount of energy released as a function of delay. The findings are that the novel method can significantly and robustly ameliorate the deleterious effects of delay, and therefore it is potentially a practical solution for implementation in MEA.

Context: KTE-X19 is a chimeric antigen receptor T-cell therapy that demonstrated efficacy with a median overall survival (OS) of 18.2 months in relapsed/refractory (R/R) adult acute lymphoblastic leukemia (aALL) patients in the pivotal ZUMA-3 trial (NCT02614066). Trials for recently approved treatments in the same setting reported median OS of fewer than 8 months. Objective: This study estimated the cost-effectiveness of KTE-X19 versus major comparators: blinatumomab (blin), inotuzumab ozogamicin (ino), and salvage chemotherapy (chemo) to treat R/R aALL patients from a US payer perspective. Design: A three-state partitioned-survival model (pre-progression survival [PPS], disease progression, and death) with a weekly cycle length estimated health outcomes and costs over a lifetime horizon. Efficacy and safety data, allogeneic stem cell transplant (allo-SCT) rates, and health state utilities were sourced directly from pivotal trials (e.g., ZUMA-3 phase 2 mITT, TOWER, INO-VATE). A mixture-cure model was used to extrapolate PPS and OS, assuming patients without disease progression after two years experienced long-term remission. Costs (including acquisition, administration, monitoring, allo-SCT, subsequent treatments, adverse events, and terminal care) were obtained from published sources. Costs and health outcomes were discounted at 3% annually. Interventions: KTE-X19 and comparators: blin, ino, and chemo. Main Outcomes Measures: The model estimated expected life years (LYs), quality-adjusted life years (QALYs), total costs for all treatments, and pairwise incremental cost-effectiveness ratios (ICERs). Results: The model showed that the incremental LY and QALY gains for KTE-X19 versus comparators were: 2.86 and 2.54 (versus blin); 4.01 and 3.37 (versus ino); and 5.65 and 4.74 (versus chemo). The incremental costs for X19 versus comparators were $51,845 (versus blin), $225,046 (versus ino), $429,720 (versus chemo), respectively. Incremental costs and QALYs gains resulted in an ICER of $20,413/QALY versus blin, $66,839/QALY versus ino, and $90,672/QALY versus chemo. At a willingness-to-pay threshold of $150,000/QALY, probabilistic sensitivity analysis demonstrated that KTE-X19 has a 92.3%, 90.2%, and 79.6% probability of being cost-effective versus blin, ino, and chemo, respectively. Conclusions: KTE-X19 is a cost-effective treatment compared to standard of care options for R/R aALL in the US. Therefore, KTE-X19 is an economically and clinically effective option to add to the current treatment landscape.

Multiple screening strategies are guideline-endorsed for average-risk colorectal cancer (CRC). The impact of real-world adherence rates on the cost-effectiveness of non-invasive stool-based CRC screening strategies remains undefined. This cost-effectiveness analysis from the perspective of Medicare as a primary payer used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC–AIM) to estimate cost and clinical outcomes for triennial multi-target stool DNA (mt-sDNA), annual fecal immunochemical test (FIT) and annual fecal occult blood test (FOBT) screening strategies in a simulated cohort of US adults aged 65 years, who were assumed to either be previously unscreened or initiating screening upon entry to Medicare. Reported real-world adherence rates for initial stool-based screening and colonoscopy follow up (after a positive stool test result) were defined as 71.1% and 73.0% for mt-sDNA, 42.6% and 47.0% for FIT, and 33.4% and 47.0% for FOBT, respectively. The incremental cost-effectiveness ratio using quality-adjusted life years (QALY) was defined as the primary outcome of interest; other cost and clinical outcomes were also reported in secondary analyses. Multiple sensitivity and scenario analyses were conducted. When reported real-world adherence rates were included only for initial stool-based screening, mt-sDNA was cost-effective versus FIT ($62,814/QALY) and FOBT ($39,171/QALY); mt-sDNA also yielded improved clinical outcomes. When reported real-world adherence rates were included for both initial stool-based screening and follow-up colonoscopy (when indicated), mt-sDNA was increasingly cost-effective compared to FIT and FOBT ($31,725/QALY and $28,465/QALY, respectively), with further improved clinical outcomes. Results are based on real-world cross-sectional adherence rates and may vary in the context of other types of settings. Only guideline-recommended stool-based strategies were considered in this analysis. Comparisons of the effectiveness and benefits of specific CRC screening strategies should include both test-specific performance characteristics and real-world adherence to screening tests and, when indicated, follow-up colonoscopy.

IntroductionChronic insomnia affects the physical and mental health, quality of life, and productivity of 6 to 10% of the adult population (15-25 million U.S. adults). Available treatments include guideline-recommended first-line cognitive behavioral therapy for insomnia (CBT-I) and medications. However, limitations such as patient access to CBT-I and limited efficacy, the presence of significant side effects, as well as safety concerns about medications limit favorable outcomes. Somryst is an FDA-authorized prescription digital therapeutic for the treatment of chronic insomnia in adults. The purpose of this analysis is to compare the effectiveness of the digital therapeutic vs CBT-I and medications for primary insomnia.MethodsChronic insomnia trials focused on digital therapeutic, CBT-I, or medication were identified in a systematic literature review. Studies using a comparator arm that cannot be considered clinically equivalent to other treatments in the network were excluded (eg, meaningfully different definition of placebo arm). A Bayesian network meta-analysis was performed in R on the mean change from baseline and the proportion of remitters using the insomnia severity index (ISI) endpoint with follow-up timepoints between 6 and 12 weeks. Mean change in ISI score from baseline was analyzed as a continuous endpoint while comparisons of the proportion of remitters were performed using odds ratios. The analysis used a random-effects model for the base case analysis. A surface under the cumulative ranking curve (SUCRA) analysis was performed to rank the treatments on each endpoint.ResultsIn total, 13 studies reported ISI mean change from baseline data. Only the digital therapeutic and CBT-I were significantly different than placebo. The digital therapeutic had the greatest mean change from baseline in ISI from placebo (−5.77 points, 95% Credible Interval (CrI) [−8.53, −3.07]), followed by CBT-I (−4.3 points, 95% CrI [−6.32, −2.39]). In the SUCRA analysis, the digital therapeutic had the highest probability (56%) of being the most effective treatment based on ISI mean change from baseline. Only 8 studies reported the proportion of ISI remitters. Only the digital therapeutic showed a statistically significant difference in remission vs placebo and had the highest odds ratio for remission vs placebo (12.33 95% CrI [2.28, 155.91]). The odds ratio for remission vs placebo in CBT-I was not statistically significant (4.08 95% CrI [0.45, 45.58]). The digital therapeutic had the highest probability (64%) of being the most efficacious for inducing remission per ISI.ConclusionsSomryst was projected to be the most effective therapy on both mean change in ISI and ISI remission within 6 to 12 weeks of treatment start vs either CBT-I or medications. Further investigation should be performed to demonstrate the long-term effectiveness of all chronic insomnia treatments.FundingPear Therapeutics

Metal intercalation into layered topological insulator materials such as the binary chalcogenide Bi2X3 (X=Te or Se) has yielded novel two-dimensional electron-gas physics, phase transitions to superconductivity, as well as interesting magnetic ground states. Of recent interest is the intercalation-driven interplay between lattice distortions, density wave ordering, and the emergence of new phenomena in the vicinity of instabilities induced by intercalation. Here, we examine the effects of Cu-intercalation on the ternary chalcogenide Bi2Te2Se. We report the discovery, in Cu0.3Bi2Te2Se, of a periodic lattice distortion at room temperature, together with a charge density wave transition around Td = 220K. We also report, for the first time, a complete study of the CuxBi2Te2Se system, and the effect of Cu-intercalation on crystal structure, phonon structure, and electronic properties for 0.0 $\le$ x $\le$ 0.5. Our electron diffraction studies reveal strong Bragg spots at reciprocal lattice positions forbidden by ABC stacking, possibly resulting from stacking faults, or a superlattice. The c-axis lattice parameter varies monotonically with x for 0 $\lt$ x $\lt$ 0.2, but drops precipitously for higher x. Similarly, Raman phonon modes $A^2_{1g}$ and $E_g$ soften monotonically for 0 $\lt$ x $\lt$ 0.2 but harden sharply for x $\gt$ 0.2. This indicates that Cu likely intercalates up to x $\sim$0.2, followed by partial site-substitutions at higher values. The resulting strain makes the 0.2 $\lt$ x $\lt$ 0.3 region susceptible to instabilities and distortions. Our results point toward the presence of an incommensurate CDW above Td = 220 K. This work strengthens prevalent thought that intercalation contributes significantly to instabilities in the lattice and charge degrees of freedom in layered chalcogenides., Comment: 11 pages, 9 figures

Energy visualization systems provide information about use in real-time to assist users with energy efficiency. In this study, three energy visualization dashboards for small businesses were developed and tested. Performance measurement, NASA Task Load Index (TLX) workload assessment, and posttest survey were used to conduct the usability testing. Compared with the dashboards that were designed using line charts and tables, a dashboard designed using visuals (e.g., gauges, pie charts, and flashing lights) produced quicker response time, lower mental and temporal demand and effort ratings, and higher ratings of engagement, interest, and trustworthiness.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. GISTs are found most commonly in the stomach; followed by the small bowel, colon and rectum, esophagus, and extragastrointestinal tract. On initial staging evaluation of GISTs, the radiologist m

Just a few weeks before the first confirmed case of novel coronavirus (COVID-19) was reported in the United States, the US Centers for Disease Control and Prevention (CDC) issued a bold promise to the nation: the agency will use its scientific expertise to bring a new level of preparedness in the United States and global health security against current and growing threats, finally eliminate certain diseases, and bring an end to the devastation of epidemics (1) The current outbreak of COVID-19 reminds us how urgent this promise is and just how critical it is to continue to sustain and strengthen our nation's public health infrastructure The unprecedented pace of the public health response to COVID-19 has only been possible because of prior investments in public health preparedness To accelerate our pace and meet the challenges of current and future health threats, we must advance our world-class data and analytics capabilities;maintain and expand our state-of-the-art public health laboratory capacity;continue building a workforce of trusted, expert, public health professionals;sustain our capacity to rapidly respond to outbreaks at their source;and assure a strong global and domestic preparedness capacity (Am J Public Health Published online ahead of print February 13, 2020: e1-e2 doi:10 2105/AJPH 2020 305618)

Objective: Clinical evidence has linked low HDL (high-density lipoprotein) cholesterol levels with high cardiovascular disease risk; however, its significance as a therapeutic target remains unestablished. We hypothesize that HDLs functional heterogeneity is comprised of metabolically distinct proteins, each on distinct HDL sizes and that are affected by diet. Approach and Results: Twelve participants were placed on 2 healthful diets high in monounsaturated fat or carbohydrate. After 4 weeks on each diet, participants completed a metabolic tracer study. HDL was isolated by Apo (apolipoprotein) A1 immunopurification and separated into 5 sizes. Tracer enrichment and metabolic rates for 8 HDL proteins—ApoA1, ApoA2, ApoC3, ApoE, ApoJ, ApoL1, ApoM, and LCAT (lecithin-cholesterol acyltransferase)—were determined by parallel reaction monitoring and compartmental modeling, respectively. Each protein had a unique, size-specific distribution that was not altered by diet. However, carbohydrate, when replacing fat, increased the fractional catabolic rate of ApoA1 and ApoA2 on alpha3 HDL; ApoE on alpha3 and alpha1 HDL; and ApoM on alpha2 HDL. Additionally, carbohydrate increased the production of ApoC3 on alpha3 HDL and ApoJ and ApoL1 on the largest alpha0 HDL. LCAT was the only protein studied that diet did not affect. Finally, global proteomics showed that diet did not alter the distribution of the HDL proteome across HDL sizes. Conclusions: This study demonstrates that HDL in humans is composed of a complex system of proteins, each with its own unique size distribution, metabolism, and diet regulation. The carbohydrate-induced hypercatabolic state of HDL proteins may represent mechanisms by which carbohydrate alters the cardioprotective properties of HDL.

Introduction: When dietary carbohydrate replaces fat, HDL cholesterol (HDL-C) and the primary HDL protein apolipoprotein A1 (apoA1) decrease. The proportion in plasma of large HDL2 decreases while small HDL3 increases. These findings suggest that diet affects metabolically important attributes of HDL that produce the size changes. We studied in humans the effect of dietary carbohydrate and unsaturated fat on the HDL proteome and metabolism of 9 HDL proteins across 5 HDL sizes. Methods and Results: Twelve participants were placed on a healthy, controlled diet high in unsaturated fat (HF) or high in carbohydrate (HC) in a randomized crossover design. At the end of each 4-week diet period, subjects were infused with a stable isotope tracer (D3-Leu) in order to label all newly synthesized HDL proteins. Blood samples were collected and tracer was followed for 70 hrs post-infusion. ApoA1-HDL was isolated by immunoaffinity purification, separated into 5 HDL particle sizes, and prepared for analysis by mass spectrometry. We used label free quantification to characterize the HDL proteome. The proteome composition and distribution across the 5 HDL sizes were remarkably conserved in all subjects on both diets. Diet altered the abundance of several proteins on the major HDL sizes alpha2 and alpha3. The HC diet increased proteins involved in lipid metabolism (apoC3, apoA2) and decreased antioxidant (PON1, PON3) and protease inhibitor (SERPINA3, SERPING1) proteins. We also monitored the metabolism of 9 proteins that likely affect HDL metabolism - apoA1, apoA2, apoA4, apoC3, apoE, apoJ, apoL1, apoM and LCAT. We used parallel reaction monitoring and XPI software to measure the amount of D3-Leu tracer over time in these 9 proteins across the 5 HDL sizes. We found that the HC diet increased apoA2 and apoJ and decreased apoA1 pool sizes on large HDL. The HC diet also increased apoM turnover in large HDL, and apoA1, apoA2, and apoE turnover across the HDL size range. Conclusions: Dietary carbohydrate when it replaces unsaturated fat alters the HDL proteome and metabolism of several HDL proteins on specific HDL sizes. Carbohydrate increases the abundance of proteins involved in lipid metabolism, decreases antioxidant and protease inhibitor proteins, and accelerates turnover of apoA1, apoA2, apoE, and apoM. This study suggests that diet modulates HDL function by affecting HDL composition and the metabolism of major HDL proteins.

Hierarchically structured materials, inspired by sophisticated structures found in nature, are finding increasing applications in a variety of fields. Here, we describe the fabrication of wrinkled gold nanoparticle films, which leverage the structural tunability of gold nanoparticles to program the wavelength and amplitude of gold wrinkles. We have carefully examined the structural evolution and tuning of these wrinkled surfaces through varying nanoparticle parameters (diameter, number of layers, density) and substrate parameters (number of axes constrained during wrinkling) through scanning electron microscopy and cross-sectional transmission electron microscopy. It is found that nanoparticle layers of sufficient density are required to obtain periodical wrinkled structures. It was also found that tuning the nanoparticle diameter and number of layers can be used to program the wrinkle wavelength and amplitude by changing the film thickness and mechanical properties. This dual degree of tunability, not previously seen with continuous films, allows us to develop one of the smallest wrinkles developed to date with tunability in the sub-100 nm regime. The effect of the induced structural tunability on the enhancement of the intensity of the 4-mercaptopyridine Raman spectra is also studied through the application of these devices as substrates for surface-enhanced Raman spectroscopy (SERS), where wrinkling proves to be an effective method for enhancing the SERS signal in cases where there is an inherently low density of gold nanoparticles.

BACKGROUND Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools and school absenteeism during the 2012-2013 influenza season. METHODS The relationship between the percent of students vaccinated in Arkansas public schools during ADH-facilitated clinics and the average daily percent of students absent from school during the 2012-2013 influenza season was quantified using linear regression modeling. The effect of increasing vaccination coverage among students on absentee days in the Arkansas public school system was estimated. RESULTS For every 1% higher vaccination coverage, 0.027% fewer absenteeism days were predicted. Larger school size was associated with higher absenteeism and predicted decreases in absenteeism were larger in magnitude for larger schools compared with smaller schools. Extrapolation of the model showed that a 10% higher vaccination level was associated with a reduction of 16-163 student absentee days per school over a 12-week influenza season. CONCLUSIONS Influenza vaccination is an effective tool to reduce school absenteeism. School-based clinics are a feasible way to target influenza vaccinations to school-aged children.