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This pretest/posttest study investigated the effectiveness of an interdisciplinary program in which occupational therapists and speech-language pathologists used a combination of video modeling, scenario-based learning, guided discussion, and reflection on the development of interpersonal skills and work readiness among students with disabilities. This study examined 20 high school and postgraduate transitional students enrolled full-time in Life Skills Support classrooms in two rural high schools. Participants completed 21 dynamic and interactive group sessions which included video modeling, scenario-based learning, guided discussion, and reflection. Sessions were completed once a week, for one hour, and focused on enhancing interpersonal skills, cognitive skills, work habits, and performance skills. Sessions were delivered via an interdisciplinary model with participants' primary occupational therapist and speech-language pathologist. Results of the paired-samples t-test found a statistically significant increase in the Becker Work Adjustment Profile-2 scores in three categories: Cognitive Skills, Work Performance, and Broad Work Adjustment. All students showed growth on Goal Attainment Scaling (GAS) T-scores; 18 of the 20 students achieved GAS T-scores greater than threshold performance.

The UV–Visible Working Group of the Network for the Detection of Atmospheric Composition Changes (NDACC) focuses on the monitoring of air-quality-related stratospheric and tropospheric trace gases in support of trend analysis, satellite validation and model studies. Tropospheric measurements are based on MAX-DOAS-type instruments that progressively emerged in the years 2010 onward. In the interest of improving the overall consistency of the NDACC MAX-DOAS network and facilitating its further extension to the benefit of satellite validation, the ESA initiated, in late 2016, the FRM4DOAS project, which aimed to set up the first centralised data processing system for MAX-DOAS-type instruments. Developed by a consortium of European scientists with proven expertise in measurements, data extraction algorithms and software design specialities, the system has now reached pre-operational status and has demonstrated its ability to deliver a set of quality-controlled atmospheric composition data products with a latency of one day. The processing system has been designed using a highly modular approach, making it easy to integrate new tools or processing updates. It incorporates advanced algorithms selected by community consensus for the retrieval of total ozone, lower tropospheric and stratospheric NO2 vertical profiles and formaldehyde profiles. The ozone and NO2 products are currently generated from a total of 22 stations and delivered daily to the NDACC rapid delivery (RD) repository, with an additional mirroring to the ESA Validation Data Centre (EVDC). Although it is still operated in a pre-operational/demonstrational mode, FRM4DOAS was already used for several validation and science studies, and it was also deployed in support of field campaigns for the validation of the TROPOMI and GEMS satellite missions. It recently went through a CEOS-FRM self-assessment process aiming at assessing the level of maturity of the service in terms of instrumentation, operations, data sampling, metrology and verification. Based on this evaluation, it falls under class C, which is a good rating but also implies that further improvements are needed to reach full compliance with FRM standards, i.e., class A.

Background: Early diagnosis of inherited metabolic diseases (IMDs) is important because treatment may lead to reduced mortality and improved prognosis. Due to their diversity, it is a challenge to diagnose IMDs in time, effecting an emerging need for a comprehensive test to acquire an overview of metabolite status. Untargeted metabolomics has proven its clinical potential in diagnosing IMDs, but is not yet widely used in genetic metabolic laboratories.Methods: We assessed the potential role of plasma untargeted metabolomics in a clinical diagnostic setting by using direct infusion high resolution mass spectrometry (DI-HRMS) in parallel with traditional targeted metabolite assays. We compared quantitative data and qualitative performance of targeted versus untargeted metabolomics in patients suspected of an IMD (n = 793 samples) referred to our laboratory for 1 year. To compare results of both approaches, the untargeted data was limited to polar metabolites that were analyzed in targeted plasma assays. These include amino acid, (acyl)carnitine and creatine metabolites and are suitable for diagnosing IMDs across many of the disease groups described in the international classification of inherited metabolic disorders (ICIMD).Results: For the majority of metabolites, the concentrations as measured in targeted assays correlated strongly with the semi quantitative Z-scores determined with DI-HRMS. For 64/793 patients, targeted assays showed an abnormal metabolite profile possibly indicative of an IMD. In 55 of these patients, similar aberrations were found with DI-HRMS. The remaining 9 patients showed only marginally increased or decreased metabolite concentrations that, in retrospect, were most likely to be clinically irrelevant. Illustrating its potential, DI-HRMS detected additional patients with aberrant metabolites that were indicative of an IMD not detected by targeted plasma analysis, such as purine and pyrimidine disorders and a carnitine synthesis disorder.Conclusion: This one-year pilot study showed that DI-HRMS untargeted metabolomics can be used as a first-tier approach replacing targeted assays of amino acid, acylcarnitine and creatine metabolites with ample opportunities to expand. Using DI-HRMS untargeted metabolomics as a first-tier will open up possibilities to look for new biomarkers.

Abstract Background The widespread clinical application of genome-wide sequencing has resulted in many new diagnoses for rare genetic conditions, but testing regularly identifies variants of uncertain significance (VUS). The remarkable rise in the amount of genomic data has been paralleled by a rise in the number of protein structures that are now publicly available, which may have clinical utility for the interpretation of missense and in-frame insertions or deletions. Methods Within a UK National Health Service genomic medicine diagnostic laboratory, we investigated the number of VUS over a 5-year period that were evaluated using protein structural analysis and how often this analysis aided variant classification. Results We found 99 novel missense and in-frame variants across 67 genes that were initially classified as VUS by our diagnostic laboratory using standard variant classification guidelines and for which further analysis of protein structure was requested. Evidence from protein structural analysis was used in the re-assessment of 64 variants, of which 47 were subsequently reclassified as pathogenic or likely pathogenic and 17 remained as VUS. We identified several case studies where protein structural analysis aided variant interpretation by predicting disease mechanisms that were consistent with the observed phenotypes, including loss-of-function through thermodynamic destabilisation or disruption of ligand binding, and gain-of-function through de-repression or escape from proteasomal degradation. Conclusions We have shown that using in silico protein structural analysis can aid classification of VUS and give insights into the mechanisms of pathogenicity. Based on our experience, we propose a generic evidence-based workflow for incorporating protein structural information into diagnostic practice to facilitate variant classification.

The UV–Visible Working Group of the Network for the Detection of Atmospheric Composition Changes (NDACC) focuses on the monitoring of air-quality-related stratospheric and tropospheric trace gases in support of trend analysis, satellite validation and model studies. Tropospheric measurements are based on MAX-DOAS-type instruments that progressively emerged in the years 2010 onward. In the interest of improving the overall consistency of the NDACC MAX-DOAS network and facilitating its further extension to the benefit of satellite validation, the ESA initiated, in late 2016, the FRM4DOAS project, which aimed to set up the first centralised data processing system for MAX-DOAS-type instruments. Developed by a consortium of European scientists with proven expertise in measurements, data extraction algorithms and software design specialities, the system has now reached pre-operational status and has demonstrated its ability to deliver a set of quality-controlled atmospheric composition data products with a latency of one day. The processing system has been designed using a highly modular approach, making it easy to integrate new tools or processing updates. It incorporates advanced algorithms selected by community consensus for the retrieval of total ozone, lower tropospheric and stratospheric NO2 vertical profiles and formaldehyde profiles. The ozone and NO2 products are currently generated from a total of 22 stations and delivered daily to the NDACC rapid delivery (RD) repository, with an additional mirroring to the ESA Validation Data Centre (EVDC). Although it is still operated in a pre-operational/demonstrational mode, FRM4DOAS was already used for several validation and science studies, and it was also deployed in support of field campaigns for the validation of the TROPOMI and GEMS satellite missions. It recently went through a CEOS-FRM self-assessment process aiming at assessing the level of maturity of the service in terms of instrumentation, operations, data sampling, metrology and verification. Based on this evaluation, it falls under class C, which is a good rating but also implies that further improvements are needed to reach full compliance with FRM standards, i.e., class A. [ABSTRACT FROM AUTHOR]

Instruments for air quality observations on geostationary satellites provide multiple observations per day and allow for the analysis of the diurnal variation in important air pollutants such as nitrogen dioxide (NO2). The South Korean instrument GEMS (Geostationary Environmental Monitoring Spectrometer), launched in February 2020, is the first geostationary instrument that is able to observe the diurnal variation in NO2. The measurements have a spatial resolution of 3.5 km × 8 km and cover a large part of Asia. This study compares 1 year of tropospheric NO2 vertical column density (VCD) observations from the operational GEMS L2 product, the scientific GEMS IUP-UB (Institute of Environmental Physics at the University of Bremen) product, the operational TROPOspheric Monitoring Instrument (TROPOMI) product, and ground-based differential optical absorption spectroscopy (DOAS) measurements in South Korea. The GEMS L2 tropospheric NO2 VCDs overestimate the ground-based tropospheric NO2 VCDs with a median relative difference of + 61 % and a correlation coefficient of 0.76. The median relative difference is - 2 % for the GEMS IUP-UB product and - 16 % for the TROPOMI product, with correlation coefficients of 0.83 and 0.89, respectively. The scatter in the GEMS products can be reduced when observations are limited to the TROPOMI overpass time. Diurnal variations in tropospheric NO2 VCDs differ by the pollution level of the analyzed site but with good agreement between the GEMS IUP-UB and ground-based observations. Low-pollution sites show weak or almost no diurnal variation. In summer, the polluted sites show a minimum around noon, indicating the large influence of photochemical loss. Most variation is seen in spring and autumn, with increasing NO2 in the morning, a maximum close to noon, and a decrease towards the afternoon. Winter observations show rather flat or slightly decreasing NO2 throughout the day. Winter observations under low-wind-speed conditions at high-pollution sites show enhancements of NO2 throughout the day. This indicates that under calm conditions, dilution and the less effective chemical loss in winter do not balance the accumulating emissions. Diurnal variation observed at a low-pollution site follows seasonal wind patterns. A weekday–weekend effect analysis shows good agreement between the different products. However, the GEMS L2 product, while agreeing with the other data sets on weekdays, shows significantly less reduction on weekends. The influence of the stratospheric contribution and the surface reflectivity product on the satellite tropospheric NO2 VCD products is investigated. While the TM5 model's stratospheric VCDs, used in the TROPOMI product, are too high, resulting in tropospheric NO2 VCDs that are too low and even negative, when used in the GEMS IUP-UB retrieval, the GEMS L2 stratospheric VCD is too low. Surface reflectivity comparisons indicate that the GEMS L2 reflectivity makes a large contribution to the observed overestimation and scatter. [ABSTRACT FROM AUTHOR]

Abstract Background Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). Methods We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. Results The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). Conclusions With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

Aims: Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer‐term outcomes among participants in PARADISE‐MI. Methods and results: In this randomized, double‐blind, active‐controlled, event‐driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run‐in. The frequency of an initial pre‐specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all‐cause mortality, and longer‐term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03–1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92–2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p‐interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all‐cause mortality, or differences in longer‐term eGFR slope. Findings were similar across the randomized treatment arms (p‐interaction >0.6 for all). Conclusions: Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer‐term kidney function. [ABSTRACT FROM AUTHOR]

Introduction Biologic and small-molecule therapies have revolutionised the treatment of moderate-to-severe inflammatory bowel disease (IBD). A significant proportion of patients experience early or delayed treatment failure. Patients with IBD with greater visceral obesity are less likely to respond to biologics. Sarcopenia has been identified as a predictor of disease severity and need for rescue therapy in acute severe ulcerative colitis. The aim of this study is to assess the feasibility of a physician-derived exercise programme in patients with IBD commencing biologic or small-molecule therapy in addition to the effect on physical fitness, body composition and objective measures of quality of life, fatigue scores and disease activity.Methods and analysis This is a randomised controlled feasibility study comparing the effects of a physician-derived exercise programme and standard medical care (biologic/small-molecule therapy) with standard care alone in patients with moderate to severe IBD. Patients with IBD in the intervention group will undergo a structured exercise programme for 20 weeks. Both IBD groups will carry out body composition, disease activity and quality-of-life assessments at baseline, week 12 and week 26. The primary objective is to assess the feasibility of the physician-derived exercise programme in patients with IBD commencing disease-modifying therapies. Secondary endpoints include a change in cardiorespiratory fitness, disease activity/inflammation, fatigue, health-related quality of life outcomes and body composition between the two IBD groups. Exploratory endpoints include validation of anterior thigh ultrasound for sarcopenia screening, assessment of proinflammatory cytokines and markers of immunometabolism.Ethics and dissemination This study has received ethical approval from the Beaumont Hospital Ethics committee on 22 October 2021 (reference number 21/21). Data generated or analysed during this study will be published as an article and supplementary appendix in relevant medical journals. The data will also be presented at national and international conferences.Trial registration number NCT05174754.

The efficiency with which ribosomes shift reading frames when decoding viral RNA may change over the course of an infection.

Abstract Background: Previously we reported the discovery of stop codon readthrough in AMD1 mRNA followed by ribosome stalling at the end of a conserved Open Reading Frame (ORF) that we termed AMD1. To explain the severe suppression of reporters fused to AMD1 tail we proposed a mechanism invoking ribosome queueing. In the original study, we tested this hypothesis, by placing the reporter stop codon in the context of readthrough permissive sequences in a dual reporter vector with downstream reporter expression driven by the EMCV IRES. In accordance with our hypothesis, we observed a striking disproportional reduction of upstream reporter activity in response to increased readthrough levels. Methods: Here we employ dual luciferase assays, western blotting and RT-qPCR to explore the effects of test sequences downstream to the reporter stop codon on its expression in dual and monocistronic reporter vectors. Results: With the dual reporter system, the disproportionate reduction of upstream reporter activity is not specific to AMD1 tail and occurs as long as the readthrough stop codon context is present at the end of the reporter’s ORF. In a monocistronic vector without an IRES, the test sequences had distinct effects which were reflective of their properties e.g., AMD1 tail inhibitory effect. We further show by employing RT-qPCR that in the IRES vectors, the Fluc activity levels measured by the luciferase assay are an accurate proxy of RNA levels. Conclusions: While our findings provide little new information regarding the functional role of AMD1 tail, they raise caution for the use of viral IRES elements in expression vectors for studying mechanisms of mRNA translation. These findings may also be pertinent to the natural properties of readthrough permissive sequences and of IRES elements, though these require a separate investigation.

Free-living amoebae (FLA) are gaining attention due to the increasing number of related grave central nervous system (CNS) and sight-threatening eye infections and their role as Trojan horses for many bacteria and viruses. This study was conducted in Assiut City, Egypt to detect the presence of FLA in different water sources using morphological and molecular approaches and determine their potential pathogenicity. A total of 188 water samples (100 tap, 80 tank, and 8 swimming pool samples) were collected, cultivated on non-nutrient agar seeded with Escherichia coli, and inspected for FLA. Thermo- and osmo-tolerance assays were performed to determine their pathogenicity. Polymerase chain reaction and sequence analysis were performed to confirm the identification and analyze the genotype. Overall, 52 samples (27.7%) were positive for FLA. Of these, 20.7% were identified as Acanthamoeba, 1.6% as Vahlkampfiidae, and 5.3% as mixed Acanthamoeba and Vahlkampfiidae. Seven species of Acanthamoeba were recognized, of which A. triangularis, A. polyphaga, A. lenticulata, and A. culbertsoni are thermo- and osmo-tolerant, and A. astronyxis, A. comandoni, and A. echinulata are non-thermo- and non-osmo-tolerant. The phylogeny analysis revealed T4 and T7 genotypes. Among Vahlkampfiids, 61.5% were identified as thermo- and osmo-tolerant Vahlkampfia, and 30.8% were identified as non-pathogenic Naegleria. One isolate (7.7%) was identified as potentially pathogenic Allovahlkampfia, as confirmed by sequencing. This is the first report documenting the occurrence and phylogeny of waterborne FLA (Acanthamoeba/Vahlkampfiidae) in Assiut, Egypt. The presence of potentially pathogenic FLA highlights the possible health hazards and the need for preventive measures.

In the past 50 years, the electronic and communication industries have grown exponentially, which has caused major concerns about electromagnetic (EM) pollution. In recent years, more thrust has been given to development of polymer composites to lessen electromagnetic interference (EMI) pollution. In the present work, porous polydimethylsiloxane (PDMS) composite foams based on cobalt ferrite (CoFe2O4) and reduced graphene oxide (rGO) are produced through the ammonium bicarbonate template approach. The resulting foams possess increased EMI shielding effectiveness via the absorption‐dominated mechanism due to the fact that PDMS foam functions as a three‐dimensional (3D) network, rGO offers the requisite conductive channel, and CoFe2O4 produces the necessary magnetic loss. The total EMI shielding effectiveness (SE) of PDMS/rGO composite foams without CoFe2O4 is 24 dB, however, with different weight percentages of CoFe2O4 added (3%, 6%, and 9%), the EMI SE increases to 41 dB for 3 mm thickness. The heat insulation performance of the material is also studied, and the measured thermal conductivity is 0.0391 Wm−1 K−1, which is very low value. The attributes of the composite foam underscore its excellent thermal insulation performance and its capacity for EMI shielding, rendering it highly suitable for diverse applications across various fields. [ABSTRACT FROM AUTHOR]