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Introduction Mental health and psychosocial support (MHPSS) staff in humanitarian settings have limited access to clinical supervision and are at high risk of experiencing burnout. We previously piloted an online, peer-supervision program for MHPSS professionals working with displaced Rohingya (Bangladesh) and Syrian (Turkey and Northwest Syria) communities. Pilot evaluations demonstrated that online, peer-supervision is feasible, low-cost, and acceptable to MHPSS practitioners in humanitarian settings. Objectives This project will determine the impact of online supervision on i) the wellbeing and burnout levels of local MHPSS practitioners, and ii) practitioner technical skills to improve beneficiary perceived service satisfaction, acceptability, and appropriateness. Methods MHPSS practitioners in two contexts (Bangladesh and Turkey/Northwest Syria) will participate in 90-minute group-based online supervision, fortnightly for six months. Sessions will be run on zoom and will be co-facilitated by MHPSS practitioners and in-country research assistants. A quasi-experimental multiple-baseline design will enable a quantitative comparison of practitioner and beneficiary outcomes between control periods (12-months) and the intervention. Outcomes to be assessed include the Kessler-6, Harvard Trauma Questionnaire and Copenhagen Burnout Inventory and Client Satisfaction Questionnaire-8. Results A total of 80 MHPSS practitioners will complete 24 monthly online assessments from May 2022. Concurrently, 1920 people receiving MHPSS services will be randomly selected for post-session interviews (24 per practitioner). Conclusions This study will determine the impact of an online, peer-supervision program for MHPSS practitioners in humanitarian settings. Results from the baseline assessments, pilot evaluation, and theory of change model will be presented. Disclosure No significant relationships.

Background. Catastrophic antiphospholipid syndrome (CAPS) is an autoimmune thrombogenic disorder of small and large vessels caused by autoantibodies against phospholipids and phospholipid-binding proteins. This severe form of antiphospholipid syndrome (APS) presents clinically with simultaneous life-threatening multiorgan thrombosis and the presence of two or more persistent antiphospholipid antibodies (APL) confirmed on testing 12 weeks apart. Case Presentation. We describe a case report of a 66-year-old woman with detected antinuclear antibodies (ANA) pretransplant diagnosed with CAPS following orthotopic liver transplant. The patient had acute respiratory failure; Doppler ultrasound and CT angiogram confirmed thrombosis in the hepatic artery, subsequent occlusion of the jump graft, and a splenic infarct. Hypercoagulability workup showed elevated levels of anticardiolipin IgG and beta-2-glycoprotein IgG/IgM and positive lupus anticoagulant, treated with steroids and anticoagulation. The patient was discharged after one month and was transitioned from heparin to life-long warfarin. Conclusion. Our patient provided a standard presentation of CAPS with abnormal pretransplant levels of antinuclear antibodies (ANA). Although there have been studies investigating the relationship between anticardiolipin antibodies and lupus anticoagulants and APS, the relationship between pretransplant positive ANA or antimitochondrial antibodies (AMA) and CAPS has yet to be explored. Further studies will be needed to determine the significance of these antibodies. We recommend preoperative APL testing for patients with positive ANA and AMA at preliver transplant presentation.

We measured respiratory flow rates, and expired O2 in 32 (2–34 years, body mass [Mb] range: 73–291 kg) common bottlenose dolphins (Tursiops truncatus) during voluntary breaths on land or in water (between 2014 and 2017). The data were used to measure the resting O2 consumption rate (V˙O2, range: 0.76–9.45 ml O2 min−1 kg−1) and tidal volume (VT, range: 2.2–10.4 l) during rest. For adult dolphins, the resting VT, but not V˙O2, correlated with body mass (Mb, range: 141–291 kg) with an allometric mass-exponent of 0.41. These data suggest that the mass-specific VT of larger dolphins decreases considerably more than that of terrestrial mammals (mass-exponent: 1.03). The average resting sV˙O2 was similar to previously published metabolic measurements from the same species. Our data indicate that the resting metabolic rate for a 150 kg dolphin would be 3.9 ml O2 min−1 kg−1, and the metabolic rate for active animals, assuming a multiplier of 3–6, would range from 11.7 to 23.4 ml O2 min−1 kg−1.\absbreak Our measurements provide novel data for resting energy use and respiratory physiology in wild cetaceans, which may have significant value for conservation efforts and for understanding the bioenergetic requirements of this species.

The past decade was characterized by an increasing scientific demand for extending towards higher repetition rates (MHz class and beyond) the performance of already operating lower repetition rate accelerator-based instruments such as x-ray free electron lasers (FELs) and ultrafast electron diffraction (UED) and microscopy (UEM) instruments. Such a need stimulated a worldwide spread of a vibrant R&D activity targeting the development of high-brightness electron sources capable of operating at these challenging rates. Among the different technologies pursued, rf guns based on room-temperature structures resonating in the very high frequency (VHF) range (30–300 MHz) and operating in continuous wave successfully demonstrated in the past few years the targeted brightness and reliability. Nevertheless, recently proposed upgrades for x-ray FELs and the always brightness-frontier applications such as UED and UEM are now requiring a further step forward in terms of beam brightness in electron sources. In this paper, we present a few possible upgrade paths that would allow one to extend, in a relatively simple and cost-effective way, the performance of the present VHF technology to the required new goals.

The Advanced Photoinjector Experiment (APEX) at the Lawrence Berkeley National Laboratory is dedicated to the development of a high-brightness high-repetition rate (MHz-class) electron injector for x-ray free-electron laser (FEL) and other applications where high repetition rates and high brightness are simultaneously required. The injector is based on a new concept rf gun utilizing a normal-conducting (NC) cavity resonating in the VHF band at 186 MHz, and operating in continuous wave (cw) mode in conjunction with high quantum efficiency photocathodes capable of delivering the required charge at MHz repetition rates with available laser technology. The APEX activities are staged in three phases. In phase 0, the NC cw gun is built and tested to demonstrate the major milestones to validate the gun design and performance. Also, starting in phase 0 and continuing in phase I, different photocathodes are tested at the gun energy and at full repetition rate for validating candidate materials to operate in a high-repetition rate FEL. In phase II, a room-temperature pulsed linac is added for accelerating the beam at several tens of MeV to reduce space charge effects and allow the measurement of the brightness of the beam from the gun when integrated in an injector scheme. The installation of the phase 0 beam line and the commissioning of the VHF gun are completed, phase I components are under fabrication, and initial design and specification of components and layout for phase II are under way. This paper presents the phase 0 commissioning results with emphasis on the experimental milestones that have successfully demonstrated the APEX gun capability of operating at the required performance.

Solid-phase microextraction (SPME) was evaluated for the detection and quantification of the gas-phase carbonyls: citronellal, glyoxal, methylglyoxal, and β-ionone. Prepared air samples containing the carbonyl compounds were collected at a flow rate of 2.8 L min−1 in an impinger containing a 25% reagent water/75% methanol collection liquid. The aqueous samples were then derivatized with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA), extracted with a PDMS/DVB coated SPME fiber, and analyzed by GC-MS. Detection limits with a sample air volume of 76 L were calculated to be 0.03 ppbv, 0.34 ppbv, 0.12 ppbv, and 0.28 ppbv for citronellal, glyoxal, methylglyoxal, and β-ionone, respectively. [ABSTRACT FROM AUTHOR]

(TtztBu,Me)CuCO [TtztBu,Me = tris(3-t-butyl-5-methyl-1,2,4-triazolyl)borate] was prepared and fully characterized to test whether the TtztBu,Me ligand, which is sterically similar to TptBu,Me is electronically different; TtztBu,Me is a weaker electron donor and (TtztBu,Me)CuCO is water stable and has a propensity to form hydrogen bonds. [ABSTRACT FROM AUTHOR]

Abstract Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons in the central nervous system (CNS). Mutations in the metalloenzyme SOD1 are associated with inherited forms of ALS and cause a toxic gain of function thought to be mediated by dimer destabilization and misfolding. SOD1 binds two Cu and two Zn ions in its homodimeric form. We have applied native ambient mass spectrometry imaging to visualize the spatial distributions of intact metal-bound SOD1G93A complexes in SOD1G93A transgenic mouse spinal cord and brain sections and evaluated them against disease pathology. The molecular specificity of our approach reveals that metal-deficient SOD1G93A species are abundant in CNS structures correlating with ALS pathology whereas fully metalated SOD1G93A species are homogenously distributed. Monomer abundance did not correlate with pathology. We also show that the dimer-destabilizing post-translational modification, glutathionylation, has limited influence on the spatial distribution of SOD1 dimers.

Abstract Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation. Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia–reperfusion injury, organ preservation strategies, and future donor‐based interventions. Important considerations include cost, public opinion regarding the conduct of animal research, translational value, and relevance of the animal model for clinical practice. We present an overview of two porcine models of organ donation: donation following brain death (DBD) and donation following circulatory death (DCD). The cardiovascular anatomy and physiology of pigs closely resembles those of humans, making this species the most appropriate for pre‐clinical research. Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation. It is imperative to minimize animal loss during procedures that are surgically complex. We present our experience with these models and describe in detail the use cases, procedural approach, challenges, alternatives, and limitations of each model.

Linear erosion channel (LEC) devastates arable land and significantly contributes to soil loss in agricultural watersheds. In the presence of a less- or non-erodible layer, channel widening governs the erosion process once the channel bed incises to this layer, accompanied by failure block generation and transport. Current knowledge on channel widening, however, is limited due to the lack of robust and efficient methods to capture the rapid sidewall expansion process. Laboratory experiments were designed to simulate the channel widening process with an initial channel width of 10 cm. Two packed soil beds with a non-erodible layer and two slope gradients (5 % and 11 %) were subjected to the inflow rate of 0.67 L/s. Images were captured by mounted digital cameras and automatically transformed into orthophotos. Channel edges and failure blocks were automatically detected by deep learning algorithm in a newly developed Channel-DeepLab network model based upon DeepLabv3+ platform. The procedure includes learning samples labelling, data augmentation, model construction, training, and validation. Sediment discharge and changes in channel width, geometry of channel edges, and failure blocks were measured. The results indicate that initial period is critical for erosion prediction and remediation due to its small sidewall failure interval, high channel expansion rate and sediment discharge. Channel surface area has great potential on accumulated sediment discharge prediction. The slope section that witnessed the fastest channel widening rate migrated downwards when slope gradient increased from 5 % to 11 %. The total number and area of the failure blocks increased with time, while the collapse frequency of the sidewalls decreased. Upstream reach experienced the highest sidewall collapse frequency and rate of disaggregation and transport, while the downstream reach experienced the highest total number of failure blocks. A time lag was found between sidewall collapse and sediment discharge, which increased as time progressed, attributing to decreased runoff erosivity as the flow velocity decreased. Results of this study will provide methodological support for channel sidewall and streambank retreat monitoring, realizing the automatic detection of channel edges and efficient output of rapid sidewall expansion process with high temporal and spatial precision. Future work can be focused on broadening the applicability of the Channel-DeepLab network model and quantifying the delayed response process between sidewall failure and sediment discharge.

Abstract Background Dengue is the most prevalent arboviral infection causing an estimated 50–60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel ‘Dengue Virus Daily Diary (DENV-DD)’, designed to measure symptom intensity and disease burden within outpatient infant to adult populations. Methods The Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness. Results Forty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3–15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion. Conclusions Findings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Abstract The European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma Questionnaire (EORTC QLQ-MY20) was developed in 1996 to assess health-related quality of life (HRQoL) in patients with multiple myeloma. Since its development new therapies have prolonged survival in patients with myeloma and new combination agents are likely to impact HRQoL outcomes and its measurement. The aim of this review was to explore the use of the QLQ-MY20 and reported methodological issues. An electronic database search was conducted (1996-June 2020) to identify clinical studies/research that used the QLQ-MY20 or assessed its psychometric properties. Data were extracted from full-text publications/conference abstracts and checked by a second rater. The search returned 65 clinical and 9 psychometric validation studies. The QLQ-MY20 was used in interventional (n = 21, 32%) and observational (n = 44, 68%) studies and the publication of QLQ-MY20 data in clinical trials increased over time. Clinical studies commonly included relapsed patients with myeloma patients (n = 15, 68%) and assessed a range of combinations therapies. QLQ-MY20 subscales (disease symptoms [DS], side effects of treatment [SE], future perspectives [FP], body image [BI]) were defined as secondary (n = 12, 55%) or exploratory (n = 7, 32%) trial endpoints, particularly DS (n = 16, 72%) and SE (n = 16, 72%). Validation articles demonstrated that all domains performed well regarding internal consistency reliability (>0.7), test-reset reliability (intraclass correlation coefficient > =0.85), internal and external convergent and discriminant validity. Four articles reported a high percentage of ceiling effects in the BI subscale; all other subscales performed well regarding floor and ceiling effects. The EORTC QLQ-MY20 remains a widely used and psychometrically robust instrument. While no specific problems were identified from the published literature, qualitative interviews are ongoing to ensure new concepts and side effects are included that may arise from patients receiving novel treatments or from longer survival with multiple lines of treatment.

BackgroundPrevious literature indicates that adolescents with developmental disabilities and obesity may have more oral health complications than healthy adolescents. However, dental care utilization among adolescents with developmental disabilities (DDs) and obesity is unclear. We investigated the differences in the utilization of preventive dental services between this high-risk group of adolescents and those with no DDs or obesity.MethodsParent-reported data of adolescents 10–17 years (n = 68,942) from the 2016 to 2019 National Survey of Children's Health was used. In addition to descriptive and bivariate statistics, we ran three multiple logistic regression models guided by Andersen's Behavioral Model of Health Services Use, predicting the use of dental cleanings, fluoride treatments, and dental sealants.ResultsAmong adolescents with DDs and obesity, dental cleanings, fluoride treatments, and dental sealant utilization prevalence were 76%, 48%, and 21%, respectively. In comparison, adolescents with no DDs or obesity had a prevalence of 83%, 50%, and 19%, respectively. Multiple logistic regression analysis showed that adolescents with DDs and obesity did not significantly differ in their receipt of dental cleanings (p = .07), fluoride treatments (p = .55), and dental sealants (p = .23) compared to those with neither DDs nor obesity. Adolescents with DDs but no obesity were 22% and 30% more likely to receive fluoride treatments (p

Abstract Background There is limited information available on the impact of moderate asthma exacerbations, often called “asthma attacks” (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients’ lives. This multi-country qualitative study explored the patient experience of these events. Methods Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients’ experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation. Results Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model. Conclusions Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients’ lives.

Abstract Background Diagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective. Methods To project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults. Results Assuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening. Conclusions Our findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.

Abstract Background Ingestion of fluoride in drinking water has been shown to result in increased cellular markers of inflammation in rodent models. However, the approximately 5–10 × increase in water fluoride concentrations required in rat and mouse models to obtain plasma fluoride concentrations similar to those found in humans has made relevant comparisons of animal to human studies difficult to assess. As an increased white blood cell count (WBC) is a marker of inflammation in humans, we used available NHANES survey data to assess the associations between plasma fluoride levels in the U.S. and blood cell counts children and adolescents. Methods Multiple linear regressions were done to determine the association of blood cell counts and plasma fluoride in publicly available NHANES survey data from the 2013–2014 and 2015–2016 cycles. Plasma fluoride concentration measurements were available only for children aged 6 to 19, inclusive, and therefore this subpopulation was used for all analyses. Covariate predictors along with plasma fluoride were age, ethnicity, gender, and Body Mass Index (BMI). Results Plasma fluoride was significantly positively associated with water fluoride, total WBC count, segmented neutrophils, and monocytes, and negatively associated with red blood cell count when adjusted for age, gender and BMI. Conclusion Our finding that neutrophils and monocytes are associated with higher plasma fluoride in U.S. children and adolescents is consistent with animal data showing fluoride related effects of increased inflammation. These findings suggest the importance of further studies to assess potential mechanisms that are involved in absorption and filtration of ingested fluoride, particularly in tissues and organs such as the small intestine, liver and kidney.

Background: Inflammation during and after surgery can lead to organ damage including acute kidney injury. Colchicine, an established inexpensive anti-inflammatory medication, may help to protect the organs from pro-inflammatory damage. This protocol describes a kidney substudy of the colchicine for the prevention of perioperative atrial fibrillation (COP-AF) study, which is testing the effect of colchicine versus placebo on the risk of atrial fibrillation and myocardial injury among patients undergoing thoracic surgery. Objective: Our kidney substudy of COP-AF will determine whether colchicine reduces the risk of perioperative acute kidney injury compared with a placebo. We will also examine whether colchicine has a larger absolute benefit in patients with pre-existing chronic kidney disease, the most prominent risk factor for acute kidney injury. Design and Setting: Randomized, superiority clinical trial conducted in 40 centers in 11 countries from 2018 to 2023. Patients: Patients (~3200) aged 55 years and older having major thoracic surgery. Intervention: Patients are randomized 1:1 to receive oral colchicine (0.5 mg tablet) or a matching placebo, given twice daily starting 2 to 4 hours before surgery for a total of 10 days. Patients, health care providers, data collectors, and outcome adjudicators will be blinded to the randomized treatment allocation. Methods: Serum creatinine concentrations will be measured before surgery and on postoperative days 1, 2, and 3 (or until hospital discharge). The primary outcome of the substudy is perioperative acute kidney injury, defined as an increase (from the prerandomization value) in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of surgery or ≥50% within 7 days of surgery. The primary analysis (intention-to-treat) will examine the relative risk of acute kidney injury in patients allocated to receive colchicine versus placebo. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by pre-existing chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate (eGFR)

Wells et al. use mathematical modeling to compare quarantine duration, testing frequency, and false-positive rate for 18 rapid antigen (RA) and RT-PCR tests. They show that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration, the timing of their use in the infection time course, and the turnaround time of test results.

Under ideal conditions, the optical path for the two counter-propagating beams in a square ring laser cavity is expected to be entirely reciprocal. This property, together with the absence of any moving parts in the gyro, makes ring lasers a very useful rotation-sensing device. For a typical aircraft application, a sensor stability of the order of 0.01 °/h and a resolution of 1 ppm is required. The demands for inertial rotation sensing in space geodesy are three orders of magnitude higher. Therefore, the perturbations from the presence of the active laser gain medium inside the cavity cannot be ignored. While these perturbations can be sufficiently contained in aviation gyros due to the much lower requirements, they cause a notable bias in large ring laser gyroscopes for the observation of the instantaneous rotation rate of the Earth. In this paper, we report on an improved model for bias stability from the presence of the laser gain medium in the gyro cavity of the large ring laser “G” at the Geodetic Observatory Wettzell. Typical values between 5 and 10 ppB are obtained over several months.

Purpose: To describe a case of foreign body giant cell reaction to silicone oil that presented as a salmon-patch conjunctival lesion. Observations: An elderly female with prior retinal surgery and oil tamponade was referred for a salmon-patch lesion in the conjunctiva. Biopsy revealed multiple vacuolations and foreign body giant cells in the substantia propria, consistent with a foreign body reaction to silicone oil. Conclusion and importance: Silicone oil can elicit an inflammatory reaction in the conjunctiva that could mimic a neoplasm. Excessive leakage of oil into the subconjunctival space should be avoided to prevent this complication.

As much as half or more of deep partial-thickness burn wounds develop hypertrophic scarring and contracture. Once formed, treatments are only minimally effective. Pirfenidone (Pf), indicated for treatment of idiopathic pulmonary fibrosis, is an anti-inflammatory and anti-fibrotic small molecule that potentially can be repurposed as a preventative against scarring in burn wounds. We present a drug-in-matrix patch with a soft skin adhesive (SSA) wound-contacting layer for multi-day drug delivery of Pf into burn wounds at the point of injury. Our patch construction consists of an SSA adhesive layer (Liveo™ MG7-9850, Dupont, Wilmington, DE, USA) for wound fixation, an acrylic co-polymer drug matrix (DURO-TAK 87-2852, Henkel, Düsseldorf, Germany) as the drug (Pf) reservoir, and an outermost protective polyurethane backing. By employing a drug-in-matrix patch design, Pf can be loaded as high as 2 mg/cm2. Compared to the acrylic co-polymer adhesive patch preparations and commercial films, adding an SSA layer markedly reduces skin stripping observed under scanning electron microscopy (SEM). Moreover, the addition of varying SSA thicknesses did not interfere with the in vitro release kinetics or drug permeation in ex vivo porcine skin. The Pf patch can be easily applied onto and removed from deep partial-thickness burn wounds on Duroc pigs. Continuous multi-day dosing of Pf by the patches (>200 μg/cm2/day) reduced proinflammatory biomarkers in porcine burn wounds. Pf patches produced by the manual laboratory-scale process showed excellent stability, maintaining intact physical patch properties and in vitro biological activity for up to one year under long-term (25 °C at 60% RH) and 6 months under accelerated (40 °C at 75% RH) test conditions. To manufacture our wound safe-and-extended-release patch, we present scale-up processes using a machine-driven automated roll-to-roll pilot scale coater.

Abstract Age-related hearing loss was recently established as the largest modifiable risk factor for Alzheimer’s disease (AD), however, the reasons for this link remain unclear. We investigate shared underlying genetic associations using results from recent large genome-wide association studies (GWAS) on adult hearing difficulty and AD. Genetic correlation and Mendelian randomization (MR) analysis do not support a genetic correlation between the disorders, but suggest a direct causal link from AD genetic risk to hearing difficulty, driven by APOE. Systematic MR analyses on the effect of other traits revealed shared effects of glutamine, gamma-glutamylglutamine, and citrate levels on reduced risk of both hearing difficulty and AD. In addition, pathway analysis on GWAS risk variants suggests shared function in neuronal signalling pathways as well as etiology of diabetes and cardiovascular disease. However, after multiple testing corrections, neither analysis led to statistically significant associations. Altogether, our genetic-driven analysis suggests hearing difficulty and AD are linked by a shared vulnerability in molecular pathways rather than by a shared genetic architecture.

PurposeWe used Andersen's Behavioral Model in a cross-sectional study to determine the factors associated with utilization of the emergency department (ED), controlling for whether an adolescent has a developmental disability (DD) and one or more oral complications (toothaches, decayed teeth, bleeding gums, eating or swallowing problems).MethodsData from the 2016–2019 National Survey of Children's Health (NSCH) was used for this secondary data analysis study. We used frequencies and percentages to describe the sample characteristics. Chi-square tests were used for bivariate analyses. Multivariable logistic regression modeling was conducted to predict ED visits by adolescents aged 10–17 controlling for predisposing, enabling, and need variables.ResultsThe sample consisted of 68,942 adolescents who were primarily male, non-Hispanic White, and born in the U.S. Parents reported that 69% of the adolescents had neither a DD nor an oral complication; 10% had no DD but experienced one or more oral complication; 16% had a DD but no oral complication; and 5% had both DDs and one or more oral complication. Adolescents with both a DD and an oral complication reported the highest level of ED visits at 33%, compared to 14% of adolescents with neither DD nor oral complication. Regression analysis showed that adolescents with a DD and oral complication (OR: 2.0, 95% CI: 1.64–2.54, p < 0.0001), and those with DDs but no oral complications (OR: 1.45, 95% CI: 1.25–1.68, p < 0.0001) were at higher odds of having an ED visit compared to those with neither a DD nor an oral complication. Not having a Medical Home increased the likelihood of ED visits by 14% (p = 0.02). Those with private insurance (OR: 0.63, 95% CI: 0.53–0.75, p < 0.0001) and those from a family where the highest level of education was some college and above (OR: 0.85, 95% CI: 0.73–0.98, p = 0.03) were less likely than their counterparts to have had an ED visit.ConclusionAdolescents with DDs and oral complications utilize ED visits more frequently than those with neither DDs nor oral complications. Integrating the dental and medical health systems and incorporating concepts of a Patient-Centered Medical Home could improve overall health care and reduce ED visits for adolescents.

We report a crystal-field analysis of Nd3+-doped KY3F10 nanocrystals. As well as electronic energy levels obtained from absorption and fluorescence, we fit to magnetic-field splittings for fields of up to 4T. The resulting parameters accurately account for the Zeeman interaction, including non-linear effects. The fitted parameters are similar to those for bulk crystals. The parameters are compared with ab-initio calculations and superposition-model analyses.

Objective: To quantify the utility of RT-PCR and rapid antigen tests in preventing post-arrival transmission based on timing of the pre-departure test.Methods: We derived analytical expressions to compute post-arrival transmission when no test is performed, and when either an RT-PCR or any of 18 rapid antigen tests is performed at specified times before arrival. We determined the diagnostic sensitivity of the rapid antigen tests by propagating their RT-PCR percent positive agreement onto known RT-PCR diagnostic sensitivity.Results: Depending on the rapid antigen test used, conducting a rapid antigen test immediately before departure reduces post-arrival transmission between 37.4% (95% CrI: 28.2%–40.7%) and 46.7% (95% CrI:40.0%–49.3%), compared to a 31.1% (95% CrI: 26.3%–33.5%) reduction using an RT-PCR 12 h before arrival. Performance of each rapid antigen test differed by diagnostic sensitivity over the course of disease. However, these differences were smaller than those engendered by testing too early.Conclusion: Testing closer to arrival—ideally on the day of arrival—is more effective at reducing post-arrival transmission than testing earlier. Rapid antigen tests perform the best in this application due to their short turnaround time.

Abstract Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case–control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E−08), rs4900545 (p = 1.8E−08) and 14:103042287_CT_C (p = 3.50E−08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p

Abstract Background Many patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA. Methods Thirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated. Results Most participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ. Conclusions This study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.

Safely reducing the necessary duration of quarantine for COVID-19 could lessen the economic impacts of the pandemic. Here, the authors demonstrate that testing on exit from quarantine is more effective than testing on entry, and can enable quarantine to be reduced from fourteen to seven days.

Summary: Background: Numerous countries have imposed strict travel restrictions during the COVID-19 pandemic, contributing to a large socioeconomic burden. The long quarantines that have been applied to contacts of cases may be excessive for travel policy. Methods: We developed an approach to evaluate imminent countrywide COVID-19 infections after 0–14-day quarantine and testing. We identified the minimum travel quarantine duration such that the infection rate within the destination country did not increase compared to a travel ban, defining this minimum quarantine as “sufficient.” Findings: We present a generalised analytical framework and a specific case study of the epidemic situation on November 21, 2021, for application to 26 European countries. For most origin-destination country pairs, a three-day or shorter quarantine with RT-PCR or antigen testing on exit suffices. Adaptation to the European Union traffic-light risk stratification provided a simplified policy tool. Our analytical approach provides guidance for travel policy during all phases of pandemic diseases. Interpretation: For nearly half of origin-destination country pairs analysed, travel can be permitted in the absence of quarantine and testing. For the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. The estimated travel quarantine durations are substantially shorter than those specified for traced contacts. Funding: EasyJet (JPT and APG), the Elihu endowment (JPT), the Burnett and Stender families’ endowment (APG), the Notsew Orm Sands Foundation (JPT and APG), the National Institutes of Health (MCF), Canadian Institutes of Health Research (SMM) and Natural Sciences and Engineering Research Council of Canada EIDM-MfPH (SMM).

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.

Abstract A 64-year-old man with a past medical history of liver transplantation on chronic immunosuppressive therapy presented with gradual worsening of vision over 2 months in his right eye. His recent history of Aspergillus and Nocardia pneumonia with positive bronchoalveolar lavage, in concert with vitritis and subretinal abscess, were concerning for endogenous endophthalmitis. A sputum culture and transbronchial lung biopsy stains grew Nocardia farcinica although aqueous humor sampling was negative. He was treated with four serial amikacin intravitreal injections over the course of 4 weeks. Pars plana vitrectomy for worsening macular traction and subsequent cataract surgery resulted in significant clinical and anatomic improvement of vision to 20/60 and consolidation of the subretinal abscess.

High-resolution infra-red spectra of KY3F10 nanoparticles doped with Nd3+and Er3+are measured in magnetic fields of up to 4T. A simple model of the magnetic splittings of the ground and excited states is used to show that the presence or absence of observable splittings depends on the anisotropy of the response to the magnetic field. Detailed crystal-field calculations accurately model the spectra, including nonlinear effects.

A valid and reliable quantitative measure of chronic pain is essential for developing and evaluating interventions that aim to treat pain. In dogs, the Canine Brief Pain Inventory (CBPI) was originally adapted from a human measure, the Brief Pain Inventory, to assess owner-perceived pain and the impact of such pain on a dog's daily functioning. To be reliable and valid, data collected using a translated instrument should have evidence it is an accurate representation of the original instrument and is culturally appropriate for use in the intended context. To achieve this, instruments should undergo a rigorous translation process and be debriefed in the intended population of use. The CBPI is widely accepted and has been fully validated for use in US-English, Swedish, Italian, and French (France); further translation and validation of the CBPI is required to increase access to and use in other languages and countries. The objective of this study was to linguistically validate the CBPI for global use (Australia, China, Germany, Hungary, Ireland, Japan, Netherlands and Portugal). In cognitive debriefing with a representative sample of dog owners in the target countries it was confirmed that the translations of the CBPI adequately convey the concepts in the original US-English version and that items are easily understood by dog owners. The results of the linguistic validation process thus produced measures that are conceptually equivalent to the original US-English-language CBPI and are culturally appropriate for use in the target countries.

OBJECTIVES:. To evaluate the link between early acute respiratory failure and functional morbidity in survivors using the plasma biomarkers interleukin-8, interleukin-1 receptor antagonist, thrombomodulin, and plasminogen activator inhibitor-1. We hypothesized that children with acute respiratory failure with higher levels of inflammation would have worse functional outcomes at discharge, as measured by Pediatric Overall Performance Category. DESIGN:. Secondary analysis of the Genetic Variation and Biomarkers in Children with Acute Lung Injury (R01HL095410) study. SETTING:. Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622) and the ancillary study (Biomarkers in Children with Acute Lung Injury). SUBJECTS:. Children 2 weeks to 17 years requiring invasive mechanical ventilation for acute airways and/or parenchymal lung disease. Patients with an admission Pediatric Overall Performance Category greater than 3 (severe disability, coma, or brain death) were excluded. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among survivors, 387 patients had no worsening of Pediatric Overall Performance Category at discharge while 40 had worsening functional status, defined as any increase in Pediatric Overall Performance Category from baseline. There was no significant relationship between worsening of Pediatric Overall Performance Category and interleukin-8 or plasminogen activator inhibitor-1 on any day. There was no significant relationship between interleukin-1 receptor antagonist, or thrombomodulin, and worsening Pediatric Overall Performance Category on day 1. Plasma interleukin-1 receptor antagonist and thrombomodulin were significantly elevated on days 2 and 3 in those with worse functional status at discharge compared with those without. In multivariable analysis, interleukin-1 receptor antagonist and thrombomodulin were associated with a decline in functional status on days 2 and 3 after adjustment for age and highest oxygenation index. However, after adjusting for age and cardiovascular failure, only day 2 thrombomodulin levels were associated with a worsening in Pediatric Overall Performance Category. CONCLUSIONS:. Higher levels of interleukin-1 receptor antagonist or thrombomodulin following intubation were associated with worse Pediatric Overall Performance Category scores at hospital discharge in children who survive acute respiratory failure. These data suggest that persistent inflammation may be related to functional decline.

Treating macaques with an anti-α4β7 antibody under the umbrella of combination antiretroviral therapy (cART) during early SIV infection can lead to viral remission, with viral loads maintained at < 50 SIV RNA copies/ml after removal of all treatment in a subset of animals. Depletion of CD8+ lymphocytes in controllers resulted in transient recrudescence of viremia, suggesting that the combination of cART and anti-α4β7 antibody treatment led to a state where ongoing immune responses kept the virus undetectable in the absence of treatment. A previous mathematical model of HIV infection and cART incorporates immune effector cell responses and exhibits the property of two different viral load set-points. While the lower set-point could correspond to the attainment of long-term viral remission, attaining the higher set-point may be the result of viral rebound. Here we expand that model to include possible mechanisms of action of an anti-α4β7 antibody operating in these treated animals. We show that the model can fit the longitudinal viral load data from both IgG control and anti-α4β7 antibody treated macaques, suggesting explanations for the viral control associated with cART and an anti-α4β7 antibody treatment. This effective perturbation to the virus-host interaction can also explain observations in other nonhuman primate experiments in which cART and immunotherapy have led to post-treatment control or resetting of the viral load set-point. Interestingly, because the viral kinetics in the various treated animals differed-some animals exhibited large fluctuations in viral load after cART cessation-the model suggests that anti-α4β7 treatment could act by different primary mechanisms in different animals and still lead to post-treatment viral control. This outcome is nonetheless in accordance with a model with two stable viral load set-points, in which therapy can perturb the system from one set-point to a lower one through different biological mechanisms.

Background: Black populations in the United States are being disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and other demographic characteristics is not well understood. We examined characteristics of individuals who died from COVID-19 in Michigan by race stratified by their age, sex and comorbidity prevalence to illustrate and understand this disparity in mortality risk. Methods: We evaluate COVID-19 mortality in Michigan by demographic and health characteristics, using individual-level linked death certificate and surveillance data collected by the Michigan Department of Health and Human Services from March 16 to October 26, 2020. We identified differences in demographics and comorbidity prevalence across race among individuals who died from COVID-19 and calculated mortality rates by age, sex, race, and number of comorbidities. Findings: Among the 6,065 COVID-19 related deaths in Michigan, Black individuals are experiencing 3·6 times the mortality rate of White individuals (p

Phytoplankton play a central role in the regulation of global carbon and nutrient cycles, forming the basis of the marine food webs. A group of biogeochemically important phytoplankton, the coccolithophores, produce calcium carbonate scales that have been hypothesized to deter or reduce grazing by microzooplankton. Here, a meta-analysis of mesocosm-based experiments demonstrates that calcification of the cosmopolitan coccolithophore, Emiliania huxleyi, fails to deter microzooplankton grazing. The median grazing to growth ratio for E. huxleyi (0.56 ± 0.40) was not significantly different among non-calcified nano- or picoeukaryotes (0.71 ± 0.31 and 0.55 ± 0.34, respectively). Additionally, the environmental concentration of E. huxleyi did not drive preferential grazing of non-calcified groups. These results strongly suggest that the possession of coccoliths does not provide E. huxleyi effective protection from microzooplankton grazing. Such indiscriminate consumption has implications for the dissolution and fate of CaCO3 in the ocean, and the evolution of coccoliths.

Knowledge of the factors influencing foraging efficiency in top predators can provide insights into the effects of environmental variability on their populations. Seabirds are important marine predators foraging in a highly temporally and spatially variable environment. While numerous studies have focussed on search time and its effects on foraging energetics in seabirds, relatively little is known about the factors influencing capture success and prey profitability in these predators. In the present study, animal-borne cameras were used to investigate the chase durations, capture success, handling durations and profitability of prey consumed by Australasian gannets (Morus serrator) (n=95) from two breeding colonies in south-eastern Australia exposed to different oceanographic conditions. Capture success was generally lower when individuals foraged alone. However, foraging in multi-species groups and in high prey densities increased chase time, while larger prey elicited longer handling times. While prey type influenced profitability, high prey density and foraging in multi-species groups was found to lower prey profitability due to increased time expenditure. While previous studies have found group foraging reduces search time, the increased profitability explains why some animals may favour solitary foraging. Therefore, future studies should combine search time and the currently found factors.

Spatio-temporal measurements of landform evolution provide the basis for process-based theory formulation and validation. Over time, field measurements of landforms have increased significantly worldwide, driven primarily by the availability of new surveying technologies. However, there is no standardized or coordinated effort within the scientific community to collect morphological data in a dependable and reproducible manner, specifically when performing long-term small-scale process investigation studies. Measurements of the same site using identical methods and equipment, but performed at different time periods, may lead to incorrect estimates of landform change as a result of three-dimensional registration errors. This work evaluated measurements of an ephemeral gully channel located on agricultural land using multiple independent survey techniques for locational accuracy and their applicability in generating information for model development and validation. Terrestrial and unmanned aerial vehicle photogrammetry platforms were compared to terrestrial lidar, defined herein as the reference dataset. Given the small scale of the measured landform, the alignment and ensemble equivalence between data sources was addressed through postprocessing. The utilization of ground control points was a prerequisite to three-dimensional registration between datasets and improved the confidence in the morphology information generated. None of the methods were without limitation; however, careful attention to project preplanning and data nature will ultimately guide the temporal efficacy and practicality of management decisions.

The RET proto-oncogene encodes a receptor tyrosine kinase that is activated by glial cell derived neutrotrophic factor (GDNF). Previous studies have found that a single nucleotide polymorphism (SNP), RETp (G691S), in the juxtamembrane domain enhances the signaling pathway and promotes tumor growth by GDNF in pancreatic and thyroid cancer in addition to melanoma. It is uncertain however whether this SNP is a germline variant or somatic mutation. A prior study reported that the RETp variant was a germline SNP in desmoplastic and non-desmoplastic melanomas. In the present study, we examined both melanoma tissue samples and matching peripheral blood DNA to determine if RETp was 1) a germline or somatic variant, 2) more frequent in certain melanoma subtypes, and 3) frequency in brain metastasis. We examined the peripheral blood of 197 melanoma patients whom had at least one matched tumor, and 42 patients with brain metastasis. RETp was present as a germline SNP in 33% of patients. There were no significant differences in RETp frequency among the different melanoma subtypes, and RETp was not correlated with brain metastasis.