Search

Oil, gas and new energy companies are facing multiple competing priorities and challenges, from ongoing high-injury rates, a challenging economic climate, reduced capital funding, increasing social pressures and disengaged talent – all leading to pressure to transform at pace. Riding the commodity price cycle and taking a piecemeal approach to transformation is no longer a viable operating strategy. An integrated approach is required, to improve safety, risk, unit cost, growth, culture and decarbonisation performance concurrently, whilst making new energy assets viable. Critical to this integrated approach is an agile, well-designed operating system. Operating systems are not new to the oil, gas and new energy industry; however, dss+ has witnessed the limited effectiveness many of them have in enabling businesses to transform holistically and rapidly. Through this presentation, dss+ will give practical guidance on the elements critical to an effective operating system, using the real-life example of a recent project which saw dss+ partnering with a global oil and gas operator to deliver a reduction in tier 1 and tier 2 safety events, reduce business operating expenditure by US$90 m, reduce capital expenditure by US$20 m and deliver an additional 350 000 boe above budget at a critical asset in the region.

IntroductionOver half of post-COVID hospitalisation adults have persistent symptoms two years after discharge providing a challenge for individuals and healthcare systems. We therefore aimed to describe a typology of UK healthcare pathways post-hospital discharge as a first step towards understanding clinical and cost-effectiveness of healthcare pathways.MethodsWe surveyed hospital sites taking part in the UK Post-hospital COVID-19 (PHOSP-COVID) study. The online survey explored availability of proactive follow-up, patient selection, involvement of multidisciplinary teams, investigations, and access to mental health and rehabilitation interventions. The typology was defined by a three-stage process: 1) using the survey results to develop a bespoke algorithm to inform a draft classification, 2) a stakeholder event for refinement, and 3) finalisation between the project advisory group and research team. The bespoke algorithm was used to map each site onto the classification with further mapping by level of mental health and rehabilitation provision.Results70% (45/64) of hospital sites responded to the survey. 82% (37/45) reported delivering a follow-up service after hospital discharge during the first few months of the pandemic. 18/37 involved temporary staffing. The final typology of five categories included no proactive follow up, and a matrix of four groups based on patient selection (pre-specified sub-group/ all patients) and complexity of assessment (low/ high). The complexity of assessment, rehabilitation and mental health interventions was variable within sites.DiscussionWe describe the first typology of post-hospitalisation COVID-19 healthcare pathways to enable modelling of clinical and cost-effectiveness to inform future policy. Our results highlight the heterogeneity and vulnerability of healthcare services after COVID-19 hospitalisation.

Information on cetacean distribution plays an important role in the identification of suitable boundaries for marine protected areas, but is also crucial for developing management and monitoring programmes. In response to the European ‘Habitats Directive’, a candidate Special Area of Conservation (cSAC) has been established in the Moray Firth, northeast Scotland to protect a small and isolated population of common bottlenose dolphins (Tursiops truncatus). Limited data on the distribution of bottlenose dolphins and on temporal changes in distribution have recently constrained attempts to mitigate against the impacts of new developments upon this population. In response to the need for current information on the distribution of dolphins throughout the cSAC, this study aims to provide data on the distribution of dolphins and other small cetaceans throughout the Moray Firth. Changes in the distribution patterns of dolphins in the inner Moray Firth were examined using data collected between 1990 and 2000. In addition, combined passive acoustic and visual survey techniques were used to determine the distribution of dolphins and harbour porpoises (Phocoena phocoena) on a broader scale across the whole Moray Firth. Dolphin schools were distributed throughout the inner Moray Firth, but there were concentrations of sightings around three deep, narrow channels that were consistent over the ten year study period. Results from surveys across the whole of the Moray Firth showed that all sightings and acoustic detections of dolphins were made within the area of the cSAC. In contrast, porpoise sightings were widely distributed throughout the Moray Firth. The median encounter rate of porpoises across the whole Moray Firth was 1.69 per 100km. Encounter rates of porpoises were similar in the outer Moray Firth and the cSAC. This combination of distribution studies at differing spatial scales provides a valuable tool for monitoring the distribution of animals and identifying important habitats, and the results of this study have directly supported efforts to manage the cSAC.

Results from previous surveys suggest that an area of the northeast Atlantic, the Faroe Shetland Channel, is important for cetaceans. This study utilised passive acoustic survey techniques to evaluate the density of sperm whales in the Channel. Two-week surveys were carried out during oceanographic cruises in May and October 2001, and May 2002. A two hydrophone array was towed behind the vessel throughout the majority of the survey routes and was monitored by a two-person team and by software designed to automatically detect and measure bearings to whales. Distances of individual sperm whales from the trackline were determined using target motion analysis. Standard line transect techniques were applied to calculate the density of whales during surveys. The effects of sea conditions and survey vessel on the ability to detect whales were tested; the encounter rate and effective stripwidth (esw) were estimated independently for each sea state and for each of the vessels. A total of 79 individual whales were detected, and their distances from the trackline were calculated. As a probable result of insufficient sample size and a small effects size, neither the esw nor the encounter rates varied significantly with sea state or between the two survey vessels. The density of sperm whales during each of the surveys was estimated to be 2.05, 0.52 and 1.75 whales per 1,000km2 for the May 2001, October 2001 and May 2002 surveys respectively. Sperm whales were distributed across the majority of the Faroe Shetland Channel. This study has provided the basis for meaningful hypothesis generation in future studies and to gain a better understanding of the factors underlying the spatial and temporal distribution patterns of sperm whales in this area; data on oceanographic, biological and anthropogenic determinants should now be examined.

The standard-of-care (SOC) diagnostic prenatal testing includes a combination of cytogenetic methods such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) using either direct or cultured amniocytes or chorionic villi sampling (CVS). However, each technology has its limitations: karyotyping has a low resolution (>5Mb), FISH is targeted, and CMA does not detect balanced structural variants (SVs) or decipher complex rearrangements in the genome. These limitations necessitate the use of multiple tests, either simultaneously or sequentially to reach a genetic diagnosis. This long-standing prenatal testing workflow demonstrates the need for an alternative technology that can provide high-resolution results in a cost and time-effective manner. Optical genome mapping (OGM) is an emerging technology that has demonstrated its ability to detect all classes of SVs, including copy number variations (CNVs) and balanced abnormalities in a single assay, but has not been evaluated in the prenatal setting. This retrospective validation study analyzed 114 samples (including replicates), representing 94 unique and well-characterized samples that were received in our laboratory for traditional cytogenetic analysis with karyotyping, FISH, and/or CMA. Samples comprised 84 cultured amniocytes, and 10 phenotypically normal and cytogenetically negative controls. Six samples were run in triplicate to evaluate intra-run, inter-run, and inter-instrument reproducibility. Clinically relevant SVs and CNVs were reported using the Bionano Access software with standardized and built-in filtration criteria and phenotype-specific analysis. OGM was 100% concordant in identifying the 101 aberrations that included 29 interstitial/terminal deletions, 28 duplications, 26 aneuploidies, 6 absence of heterozygosity (AOH), 3 triploid genomes, 4 Isochromosomes, 1 translocation, and revealed the identity of 3 marker chromosomes, and 1 chromosome with additional material not determined by karyotyping. Additionally, OGM detected 64 additional clinically reportable SVs in 43 samples. OGM demonstrated high technical and analytical robustness and a limit of detection of 5% allele fraction for interstitial deletions and duplications, and 10% allele fraction for translocation and aneuploidy. This study demonstrates that OGM has the potential to identify unique genomic abnormalities such as CNVs, AOHs, and several classes of SVs including complex structural rearrangements. OGM has a standardized laboratory workflow and reporting solution that can be adopted in routine clinical laboratories and demonstrates the potential to replace the current SOC methods for prenatal diagnostic testing. We recommend its use as a first-tier genetic diagnostic test in a prenatal setting.

In 1995 small-scale excavations undertaken at Cramond, Edinburgh revealed a number of pit and post hole features related to temporary or intermittent Mesolithic occupation. These features and associated deposits produced sizeable assemblages of charred plant remains and lithic material. Cramond appears to be the first of an increasing number of securely dated narrow-blade microlithic sites excavated in recent times along the Forth Littoral. Together with substantial house sites such as Echline Fields, East Barns and Howick, Cramond produced a narrow-blade microlithic industry associated with occupation during the mid-9th millennium BC. As such it remains the earliest narrow-blade type assemblage yet discovered in Britain and provides a jumping off point for the discussion of Mesolithic responses to a rapidly changing environment in terms of population movement and technological change.

Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Is consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?We retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEVBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEVDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Almost all babies are breastfed in Papua New Guinea (PNG); yet appropriate breastfeeding practices are not always followed.To explore the perspectives of first-time mothers in rural PNG on how the language and discourse of grandmothers about infant feeding influence their breastfeeding practices.A critical discourse analysis (CDA) approach was used to theoretically frame the analysis of twenty first-time mothers' narratives.Analysis revealed three themes: (i) prescribed knowledge repository, (ii) social control and dominance, and (iii) disapproval and role conflict, which provides an understanding of grandmothers' differing views and positions on infant feeding practices and their influence on breastfeeding.This study shows that grandmothers remain influential in infant feeding practices in rural PNG. There appears to be a societal expectation that empowers grandmothers in the maternal decision-making processes regarding breastfeeding practice. Grandmothers' influence includes the early introduction of complementary foods to infants less than six months old. Interventions aimed at promoting, protecting, and supporting breastfeeding need to include grandmothers.

Discriminating Archean Au deposit types and related ore-forming processes is challenging but paramount for increasing Au exploration success. This study tests the validity of applying geochemical data generated from conventional bulk versus modern in situ methods as discriminants for classifying Au deposits in the Archean Swayze greenstone belt with further comparison to other deposits in the contiguous Abitibi greenstone belt and Red Lake area (Superior Province, Canada). The study used five well-characterized Au settings, based on new mapping, as a basis for evaluating in situ (δ18Oquartz, δ33, 34Ssulfide, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis of pyrite, electron microprobe analysis of gold), and whole-rock geochemical datasets to resolve whether intrusion-related Au deposits can be discriminated from orogenic-type Au deposits. Results show that the in situ methods provide insight into processes related to Au mineralization, both primary and subsequent remobilization and upgrading, and define elemental and isotopic correlations that cannot be resolved using conventional bulk methods. For example, when comparing the whole-rock to laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) trace metal data, only Ag, Te, and Hg show a consistent positive correlation with Au across deposit types in both data sets. Furthermore, the wholerock datasets combined with in situ isotopic analysis suggest the Archean sanukitoid-associated Au deposits represent a distinct group of intrusion-related deposits with mineralization characterized by low δ34Spyrite (

This paper begins with the premise that the purpose of physical education is to help young people grow personal and durable playgrounds. That is, its goal is to allow students in schools to develop the skills and understandings about various movement topics to the extent that they can engage with these in deep and meaningful ways long after their lessons in the gymnasium have concluded. The paper presents a schematic that links how a physical education curriculum should be framed with the necessary ingredients of high-quality teaching to allow for successful forays into various movement cultures. The next section includes a justification of the schema using the very best of research in sport pedagogy that has been translated into school physical education settings. Two specific grand adventures that are the vehicles for creating enduring playgrounds are presented, these being sport education and student-designed games.

Nicotine from cigarette smoke is a biologically active molecule that has pleiotropic effects in the airway, which could play a role in smoking-induced lung disease. However, whether nicotine and its metabolites reach sustained, physiologically relevant concentrations on airway surfaces of smokers is not well defined. To address these issues, concentrations of nicotine, cotinine, and hydroxycotinine were measured by mass spectrometry (MS) in supernatants of induced sputum obtained from participants in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS), an ongoing observational study that included never smokers, former smokers, and current smokers with and without chronic obstructive pulmonary disease (COPD). A total of 980 sputum supernatants were analyzed from 77 healthy never smokers, 494 former smokers (233 with COPD), and 396 active smokers (151 with COPD). Sputum nicotine, cotinine, and hydroxycotinine concentrations corresponded to self-reported smoking status and were strongly correlated to urine measures. A cutoff of ∼8–10 ng/mL of sputum cotinine distinguished never smokers from active smokers. Accounting for sample dilution during processing, active smokers had airway nicotine concentrations in the 70–850 ng/mL (∼0.5–5 µM) range, and concentrations remained elevated even in current smokers who had not smoked within 24 h. This study demonstrates that airway nicotine and its metabolites are readily measured in sputum supernatants and can serve as biological markers of smoke exposure. In current smokers, nicotine is present at physiologically relevant concentrations for prolonged periods, supporting a contribution to cigarette-induced airway disease.

Lightweight fibre-reinforced thermoplastic (FRTP) driveshafts are ideal for automotive applications. In this work, material and buckling failures of FRTP driveshafts subjected to torsion at elevated temperature are analysed by finite element modelling. Critical speed at increasing temperature is also quantified. The driveshafts comprise unidirectional carbon/polyetheretherketone (PEEK) layers with/without an inner layer of aluminium or unreinforced plastic. Temperature-dependent material properties are considered. The results demonstrate achievable performance of the fully carbon/PEEK and hybrid driveshafts, which are compared with traditional alloy counterparts. The carbon/PEEK shaft exhibits marked temperature sensitivity but satisfies the design requirements at high temperature with significant weight reduction. A hybrid shaft composed of carbon/PEEK layers over-wrapped onto an aluminium tube provides a compromise in terms of superior buckling resistance and critical speed but reduced material failure safety factor. Utilising a thick layer of unreinforced plastic to reduce fibre volume may only be suitable for low-temperature, low-speed applications.

The current standard-of-care cytogenetic techniques for the analysis of hematological malignancies include karyotyping, fluorescence in situ hybridization, and chromosomal microarray, which are labor intensive and time and cost prohibitive, and they often do not reveal the genetic complexity of the tumor, demonstrating the need for alternative technology for better characterization of these tumors. Herein, we report the results from our clinical validation study and demonstrate the utility of optical genome mapping (OGM), evaluated using 92 sample runs (including replicates) that included 69 well-characterized unique samples (59 hematological neoplasms and 10 controls). The technical performance (quality control metrics) resulted in 100% first-pass rate, with analytical performance (concordance) showing a sensitivity of 98.7%, a specificity of 100%, and an accuracy of 99.2%. OGM demonstrated robust technical, analytical performance, and interrun, intrarun, and interinstrument reproducibility. The limit of detection was determined to be at 5% allele fraction for aneuploidy, translocation, interstitial deletion, and duplication. OGM identified several additional structural variations, revealing the genomic architecture in these neoplasms that provides an opportunity for better tumor classification, prognostication, risk stratification, and therapy selection. Overall, OGM has outperformed the standard-of-care tests in this study and demonstrated its potential as a first-tier cytogenomic test for hematologic malignancies.

Aims: An automated method for the measurement of blood tacrolimus on volumetric absorptive microsampling (VAMS) devices was developed. Materials & methods: VAMS devices prepared by the automated method were compared with those prepared by the existing manual method (n = 284; mean concentration: 8.0 μg/l; range: 0.6–18.1). Results: The performance of both methods was comparable. Passing–Bablok regression demonstrated an acceptable correlation (y = -0.449 + 1.06x). Bland-Altman analysis demonstrated acceptable agreement (mean bias: -0.007 μg/l; standard deviation: 1.536). Automation reduced operator touch time by 40 min (48-sample batch). Conclusion: Automated preparation of VAMS devices reduced touch time and improved process consistency, facilitating high-throughput testing and transformation of existing laboratory workflows. Automation did not improve precision for VAMS devices but did so for liquid blood samples.

The current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has benefitted society1,2. However, it still has many gaps and errors, and does not represent a biological genome as it is a blend of multiple individuals3,4. Recently, a high-quality telomere-to-telomere reference, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a nearly homozygous genome5. To address these limitations, the Human Pangenome Reference Consortium formed with the goal of creating high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and assembly approaches yield the most complete and accurate diploid genome assembly with minimal manual curation. Approaches that used highly accurate long reads and parent–child data with graph-based haplotype phasing during assembly outperformed those that did not. Developing a combination of the top-performing methods, we generated our first high-quality diploid reference assembly, containing only approximately four gaps per chromosome on average, with most chromosomes within ±1% of the length of CHM13. Nearly 48% of protein-coding genes have non-synonymous amino acid changes between haplotypes, and centromeric regions showed the highest diversity. Our findings serve as a foundation for assembling near-complete diploid human genomes at scale for a pangenome reference to capture global genetic variation from single nucleotides to structural rearrangements.

Chromosome 16p11.2 reciprocal genomic disorder, resulting from recurrent copy-number variants (CNVs), involves intellectual disability, autism spectrum disorder (ASD), and schizophrenia, but the responsible mechanisms are not known. To systemically dissect molecular effects, we performed transcriptome profiling of 350 libraries from six tissues (cortex, cerebellum, striatum, liver, brown fat, and white fat) in mouse models harboring CNVs of the syntenic 7qF3 region, as well as cellular, transcriptional, and single-cell analyses in 54 isogenic neural stem cell, induced neuron, and cerebral organoid models of CRISPR-engineered 16p11.2 CNVs. Transcriptome-wide differentially expressed genes were largely tissue-, cell-type-, and dosage-specific, although more effects were shared between deletion and duplication and across tissue than expected by chance. The broadest effects were observed in the cerebellum (2,163 differentially expressed genes), and the greatest enrichments were associated with synaptic pathways in mouse cerebellum and human induced neurons. Pathway and co-expression analyses identified energy and RNA metabolism as shared processes and enrichment for ASD-associated, loss-of-function constraint, and fragile X messenger ribonucleoprotein target gene sets. Intriguingly, reciprocal 16p11.2 dosage changes resulted in consistent decrements in neurite and electrophysiological features, and single-cell profiling of organoids showed reciprocal alterations to the proportions of excitatory and inhibitory GABAergic neurons. Changes both in neuronal ratios and in gene expression in our organoid analyses point most directly to calretinin GABAergic inhibitory neurons and the excitatory/inhibitory balance as targets of disruption that might contribute to changes in neurodevelopmental and cognitive function in 16p11.2 carriers. Collectively, our data indicate the genomic disorder involves disruption of multiple contributing biological processes and that this disruption has relative impacts that are context specific.

Malnutrition is associated with worse outcomes post-haematopoietic stem cell transplantation, with nutrition support recommended for people who are malnourished or have prolonged inadequate energy intake. We investigated associations between nutritional status, nutrition support type and clinical outcomes in adults with multiple myeloma post stem cell transplantation.Medical records (2015-2020) were reviewed to retrieve demographics, anthropometry, dietary data, nutrition support type (enteral/oral versus parenteral), and clinical outcomes (engraftment time, infection, length of stay, weight changes). Relationships were examined using linear regression modelling and Fisher's exact test.One hundred thirteen participants were included (61% male; median age 62 years). Fifteen participants (13%) received parenteral and 98 (87%) received enteral/oral nutrition support. Parenteral nutrition was associated with shorter platelet engraftment time by 2.7 days (p = 0.036) and a longer hospital stay by 6.1 days (p 0.001). Nutrition support was not associated with neutrophil engraftment time (p = 0.365). Inadequate energy intake for ≥ 7 days was not associated with any clinical outcomes (p 0.05).Participants who received parenteral nutrition reached platelet engraftment sooner but were in hospital longer. Inadequate energy intake for ≥ 7 days did not impact clinical outcomes. Multi-site prospective studies are warranted to confirm results.

Funding came from the Scottish Funding Council’s MASTS pooling initiative (Marine Alliance for Science and Technology for Scotland; grant ref. HR09011), Harper Macleod LLP, and the University of the Highlands and Islands (UHI). 1. Bottlenose dolphin photo-identification data were compiled from western Scotland to identify individuals and ultimately investigate population size, demographic parameters, spatio-temporal distribution, and movement patterns. 2. Opportunistic citizen science photographs revealed what appeared to be an adult bottlenose × Risso’s dolphin hybrid along with an apparent second-generation hybrid or back-cross calf. Both had atypically short rostra and the dorsal fin of the adult was noticeably taller than is normal for bottlenose dolphins. 3. Based on these characteristics, this case may represent a congenital rostral abnormality or the first intergeneric calf reported for this species combination, either in captivity or in the wild. 4. The previously reported presence of several putative hybrids and mixed-species sightings in the area, in combination with the tall dorsal fin, provide support for the second possibility, i.e. intergeneric hybrids. 5. Although rare, hybridization may have disproportionate conservation consequences, with population-level impacts in very small coastal populations of long-lived, slow-breeding animals. Publisher PDF

Objective This study aimed to investigate the use of the head and neck cancer risk calculator version 2 in a primary care setting and to evaluate the impact of the risk calculator on the number of referrals stratified by urgency and cancer yield. Method Referrals between April 2019 and August 2019, April 2020 and July 2020 (pre-risk calculator) and August 2020 and July 2021 (post-risk calculator) were analysed. Referral urgency, head and neck cancer risk calculator version 2 score, cancer diagnosis, cancer type and further investigations were recorded. Results The 2023 patient encounters were analysed; there were 1110 (55 per cent) referrals before head and neck cancer risk calculator version 2 use and 913 (45 per cent) after head and neck cancer risk calculator version 2 use. A higher proportion of older (p < 0.001) and male (p < 0.013) patients were seen post-head and neck cancer risk calculator version 2 use. All cancer cases were seen on the urgent suspicion of cancer pathway post-head and neck cancer risk calculator version 2 use; however, a higher proportion of patients were seen as urgent suspicion of cancer (51.1 vs 83.5 per cent; p < 0.001). Overall, the cancer diagnosis rate increased from 2.7 to 4.1 per cent. Conclusion The head and neck cancer risk calculator version 2 had high sensitivity in cancer diagnosis. More studies are required to optimise the predicted versus actual cancer probability gap.

Teak is one type of tree that has many functions and uses. Teak wood has a very high quality to be used as raw material for the manufacture of home furniture such as tables, chairs, cabinets, and others. But middle testers (Perhutani staff) who test the quality of wood grade have limitations if the classification uses the five senses of sight and also there are still many furniture entrepreneurs who are often mistaken about teak wood quality assessment. This resulted in a lack of quality grade teak wood used as raw material for making home appliances or for furniture and trade needs under the Perhutani Corporation, especially the Cepu Kph. The teak wood image data is then acquired through preprocessing data ready to be processed. By using GLCM as an image feature extraction both training data and testing data. After the image characteristics are obtained, the image is classified by the K-Nearest Neighbor method with adaboost optimization. The final result is obtained in the form of wood grade quality classification namely grade A, B, C and D according to the class

Purpose: The purpose of this study was to examine the effects of Play Practice instruction on the badminton content knowledge and skill of a cohort of Chinese physical education majors. Method: Seventy-two second-year students participated in semester-long courses following either the principles of Play Practice or skill-focused instruction. A control/comparison group experimental design with pre- and postmeasures was used in this study. Separate analyses of variance with repeated measures (Time × Group) were conducted to examine the effects of Play Practice and skill-focused instruction for each of four dependent variables: (a) forehand clear, (b) tactical understanding, (c) game performance, and (d) specialized content knowledge. Results: Students from both conditions made significant improvements in all four variables across the semester. However, students in the Play Practice condition showed significantly greater gains in tactical understanding, game performance, and specialized content knowledge. In particular, while 75% of students who experienced Play Practice reached the 3.0 benchmark score for adequate specialized content knowledge, only 8% of students in skill-focused instruction reached this standard.

A significant barrier to improving prevention and treatment of postpartum hemorrhage (PPH) is a lack of innovative medicines that meet the needs of women and providers, particularly those in low-and middle-income countries (LMICs). The Accelerating Innovation for Mothers (AIM) project established a new database of candidate medicines under development for five pregnancy-related conditions between 2000 and 2021.To systematically identify and rank candidates for prevention and treatment of PPH.Adis Insight, Pharmaprojects, WHO ICTRP, PubMed, and grant databases were searched to develop the AIM database.AIM database was searched for candidates being evaluated for PPH prevention and treatment, regardless of phase.Candidates were ranked as high, medium, or low potential based on prespecified criteria. Analysis was primarily descriptive, describing candidates and development potential.Of the 444 unique candidates, only 39 pertained to PPH. One was high potential (heat-stable/inhaled oxytocin) and three were medium potential (melatonin, vasopressin and dofetilide via nanoparticle delivery).The pipeline for new PPH medicines is concerningly limited, lacking diversity, and showing little evidence of novel technologies. Without significant investment in early-phase research, it is unlikely that new products will emerge.

The limited amount of research on the influence of social status during group work in physical education has typically focused on interactions and power. What is less understood is whether social status has an impact on various physical education outcomes. The purpose of this study was to examine physical activity, game performance, and knowledge outcomes of high- and low-status fifth-grade students during a physical education field hockey unit delivered utilising the Sport Education model. 44 students completed sociometric peer nomination surveys to determine the social status hierarchy of all students in the class. Students wore accelerometers to measure moderate to vigorous physical activity (MVPA) during the unit. Pre- and post-unit game performance and knowledge were assessed through the Team Sport Assessment Procedure and cognitive tests, respectively. Repeated measures analysis of variance showed no significant difference between high- and low-status students’ average MVPA over all phases of the unit (pre-season, season and post-season), while analysis of covariances revealed significant differences in game performance and field hockey knowledge based on social status. Results suggest while physical activity levels were similar between high- and low-status students, some lower-status students were at risk in terms of developing skills and knowledge.

BACKGROUND: Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets. RESEARCH QUESTION: Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations? STUDY DESIGN AND METHODS: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations. RESULTS: Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations. INTERPRETATION: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov

The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P -value0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P -value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

Purpose: This study examined the pedagogical experiences of former graduate teaching assistants following their teaching experiences at a youth development center. Method: A case study approach was utilized to investigate each participant case while a phenomenological approach was employed to analyze each case. The participants, Malik, Dante, and Ray, previously taught physical education at a youth development center as graduate teaching assistants. Results: The results of this study are presented as three cases centered on the participants and their experiences. The first case, “developing people from where they are, not where you want them to be . . .” (Malik) highlights the participants’ appreciation of their students’ culture and context. The second case, “resiliency to teach well regardless of circumstance or situation . . .” (Dante) features the participants’ ability to teach diverse learners. The third case, “uphill battles . . . you cannot learn this in a textbook . . .” (Ray) features the challenges faced while teaching at the youth development center. Discussion: Consistencies across participants’ experiences, the impact on their current careers, and implications for introducing culturally relevant and sustaining pedagogies via nontraditional settings are discussed.

Inland waters are important sources of the greenhouse gasses (GHGs) carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) to the atmosphere. While a growing number of global estimates of inland water GHG emissions exists, the integration of inland waters into regional GHG budgets is often hampered by the lack of adequate geo-spatial datasets. Moreover, existing estimates diverge substantially, in part due to persisting uncertainties related to the size and distribution of effective inland water surface areas. In the framework of the 2nd phase of the REgional Carbon Cycle Assessment and Processes (RECCAP-2) initiative, we synthesize existing estimates of GHG emissions from streams, rivers, lakes and reservoirs, and homogenize them with regard to underlying global maps of inland water surface areas and the effects of seasonal ice cover. We then produce estimates of inland water GHG emissions for 10 extensive land regions that are used for the regional land budgets of RECCAP2. According to our synthesis, global inland waters emit 5.6 (3.5-9.1) Pg CO2 yr-1, 101 (83-135) Tg CH4 yr-1 and 326 (254-592) Gg N2O yr-1. South American rivers contribute about one third of global inland water CO2 emissions. North-American and Russian lakes contribute together one third of global inland water CH4 emissions. Finally, North America alone contributes one fourth of global inland water N2O emissions.The global inland water emissions sum up to a global warming potential (GWP) of an equivalent emission of 13.6 (10.0-20.3) and 8.3 (5.8-12.7) Pg CO2 yr-1 at a 20- and 100-year horizon, respectively. At 100-year horizon, the contribution of CO2 dominates the GWP of global inland water GHG emissions, with rivers being the largest emitters. At the 20-year horizon, on the contrary, lakes and rivers are equally important emitters, and the contributions of CH4 to the GWP of inland water GHG emissions even exceed those of CO2. Contributions of N2O to the GWP appear to be less significant at both time horizons. Normalized to the area of the RECCAP-2 land regions, South America and South East Asia show the highest inland water emission rates in terms of GWP, dominated by riverine CO2 emissions.

Abstract Characterization of live biotherapeutic product (LBP) batches typically includes a measurement of viability, such as colony forming units (CFU). However, strain-specific CFU enumeration assays can be complicated by the presence of multiple organisms in a single product with similar growth requirements. To overcome specific challenges associated with obtaining strain-specific CFU values from multi-strain mixtures, we developed a method combining mass spectrometry-based colony identification with a traditional CFU assay. This method was assessed using defined consortia made from up to eight bacterial strains. Among four replicate batches of an eight-strain mixture, observed values differed from expected values by less than 0.4 log10 CFU among all strains measured (range of differences, -0.318 to + 0.267). The average difference between observed and expected values was + 0.0308 log10 CFU, with 95% limits of agreement from -0.347 to 0.408 (Bland–Altman analysis). To estimate precision, a single batch of eight-strain mixture was assayed in triplicate by three different users, for a total of nine measurements. Pooled standard deviation values ranged from 0.067 to 0.195 log10 CFU for the eight strains measured, and user averages did not differ significantly. Leveraging emerging mass-spectrometry-based colony identification tools, a novel method for simultaneous enumeration and identification of viable bacteria from mixed-strain consortia was developed and tested. This study demonstrates the potential for this approach to generate accurate and consistent measurements of up to eight bacterial strains simultaneously and may provide a flexible platform for future refinements and modifications. Key points • Enumeration of live biotherapeutics is essential for product quality and safety. • Conventional CFU counting may not differentiate between strains in microbial products. • This approach was developed for direct enumeration of mixed bacterial strains simultaneously.