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Within schools, school counsellors are often delegated the responsibility for reporting child maltreatment. In this paper, we present findings of a rapid review of empirical studies investigating what is known about school counsellors' reporting of child maltreatment. Thematic categories identified include school counsellors' training, knowledge, factors influencing reporting, and reporting experiences. These themes appear to act independently, in overlap, or collectively as facilitators and barriers to school counsellors' effective reporting practices. The rapid review findings will guide future education and training initiatives to prepare school counsellors for their work in schools. Directions for future research are proposed.

This study aims to explore the experiences of academics and students at undergraduate programmes at two schools of business, one in Australia and the other in Finland, regarding the process of research-based learning (RBL) and the accompanying development of students' skills. Employing an ethnographic case study method, data is collected through semi-structured interviews with seven students and four academics from the two institutions. Results suggest that RBL is challenging for undergraduate students but equally rewarding for developing their work readiness and professional identity skills. Moreover, findings also reveal that the supervisor has a central role in managing the complexities of the RBL process.

Abstract More than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most of these infections but resistance is rising, therefore the identification of antifungal targets whose inhibition synergises with the azoles could improve therapeutic outcomes. Here, we generate a library of 111 genetically barcoded null mutants of Aspergillus fumigatus in genes encoding protein kinases, and show that loss of function of kinase YakA results in hypersensitivity to the azoles and reduced pathogenicity. YakA is an orthologue of Candida albicans Yak1, a TOR signalling pathway kinase involved in modulation of stress responsive transcriptional regulators. We show that YakA has been repurposed in A. fumigatus to regulate blocking of the septal pore upon exposure to stress. Loss of YakA function reduces the ability of A. fumigatus to penetrate solid media and to grow in mouse lung tissue. We also show that 1-ethoxycarbonyl-beta-carboline (1-ECBC), a compound previously shown to inhibit C. albicans Yak1, prevents stress-mediated septal spore blocking and synergises with the azoles to inhibit A. fumigatus growth.

Objectives: Short child occupational profile (SCOPE) screening tool is used to assess different factors of functional abilities and record the progress levels of individuals in occupational therapy interventions. This study aimed to validate a Persian version of the SCOPE test. Methods: This methodological research was conducted in two stages, including translation and psychometric properties. A total of 182 people aged 3-21 years were recruited using the convenience sampling method for the second stage. Results: The results of the content validity of the questionnaire were in acceptable ranges. The total intra-class correlation coefficient and total Cronbach's α were 0.97 and 0.93, respectively. The results of the discriminant validity between the normal and disabled groups showed significant differences between the normal and disabled groups in all items of the questionnaire. Discussion: The findings demonstrated that the Persian version of the SCOPE questionnaire could be used as a valid and reliable tool.

Background Despite the increasing availability of electronic healthcare record (EHR) data and wide availability of plug-and-play machine learning (ML) Application Programming Interfaces, the adoption of data-driven decision-making within routine hospital workflows thus far, has remained limited. Through the lens of deriving clusters of diagnoses by age, this study investigated the type of ML analysis that can be performed using EHR data and how results could be communicated to lay stakeholders.Methods Observational EHR data from a tertiary paediatric hospital, containing 61 522 unique patients and 3315 unique ICD-10 diagnosis codes was used, after preprocessing. K-means clustering was applied to identify age distributions of patient diagnoses. The final model was selected using quantitative metrics and expert assessment of the clinical validity of the clusters. Additionally, uncertainty over preprocessing decisions was analysed.Findings Four age clusters of diseases were identified, broadly aligning to ages between: 0 and 1; 1 and 5; 5 and 13; 13 and 18. Diagnoses, within the clusters, aligned to existing knowledge regarding the propensity of presentation at different ages, and sequential clusters presented known disease progressions. The results validated similar methodologies within the literature. The impact of uncertainty induced by preprocessing decisions was large at the individual diagnoses but not at a population level. Strategies for mitigating, or communicating, this uncertainty were successfully demonstrated.Conclusion Unsupervised ML applied to EHR data identifies clinically relevant age distributions of diagnoses which can augment existing decision making. However, biases within healthcare datasets dramatically impact results if not appropriately mitigated or communicated.

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

The use of nature-based solutions (NbS) to address the risks posed by hydro-meteorological hazards have not yet become part of the mainstream policy response, and one of the main reasons cited for this, is the lack of evidence that they can effectively reduce disaster risk. This paper addresses this issue, by providing model-based evidence from five European case studies which demonstrate the effectiveness of five different NbS in reducing the magnitude of the hazard and thus risk, in present-day and possible future climates. In OAL-Austria, the hazard is a deep-seated landslide, and the NbS analysed is afforestation. Modelling results show that in today's climate and a landcover scenario of mature forest, a reduction in landslide velocity of 27.6 % could be achieved. In OAL-Germany, the hazard is river flooding and the NbS analysed is managed grazing with removal of woody vegetation. Modelling results show that the NbS could potentially reduce maximum flood water depth in the near-future (2031–2060) and far-future (2070–2099), by 0.036 m and 0.155 m, respectively. In OAL-Greece, the hazard is river flooding, and the NbS is upscaled natural storage reservoirs. Modelling results show that in a possible future climate the upscaled NbS show most potential in reducing the total flooded area by up to 1.26 km2. In OAL-Ireland, the hazard is surface and river flooding, and the NbS is green roofs. Results from a modelled upscaling analysis under two different climate scenarios show that both maximum flood water depth, and total flooded area were able to be reduced. In OAL-UK, the hazard is shallow landslides, and the NbS is high-density planting of two different tree species. Modelling results under two different climate scenarios show that both tree species were able to improve slope stability, and that this increased over time as the NbS matured. The significance of these results is discussed within the context of the performance of the NbS over time, to different magnitude events, impact with stakeholders in engendering wider support for the adoption of the NbS in the OALs, and the uncertainty in the modelling analyses.

Illawarra plum (IP) is a fruit native to Australia and is a source of antioxidants including phenolics and anthocyanins which contribute important functions in food preservation and quality. However, the retention of natural antioxidants is influenced by thermal processing due to their sensitivity to heat. This study measured the impact of three common drying methods to identify the best processing conditions, including cost effectiveness on retaining the quality of IP. The colour (L*, a*, b*), levels of total phenolics, flavonoids, proanthocyanidins, anthocyanins and antioxidant scavenging capacity of the samples were measured on dried IP fruits (freeze dried, convection oven 70, 90, 110 °C or vacuum oven 70, 90 or 110 °C). The freeze dried sample observed the best colour (L* 44.18±0.50, a* 16.72±0.15, b* 1.66±0.04) and highest levels of compounds from the methods observed: TPC 679.19±15.04 mM GAE/g DW, TFC 190.25±4.65 mM CE/g DW, proanthocyanidins 422.46 ± 21.52 mM CE/g DW, DPPH 562.51±40.69 mM TE/g DW, monomeric anthocyanins 402.58±3.97 µg C3G/L DW and 57.97±2.84 % polymeric anthocyanins. For maximum retention of quality, freeze drying is recommended, however, it is costly and for a more economical approach, vacuum drying at 90 °C or convection oven drying at 110 °C are identified as suitable conditions for drying IP to prevent unnecessary loss of phenolic quality, however these methods will cause shrinkage and browning in the fruit. These conditions can be applied for drying IP for direct use as a dried product or for further applications in food

Abstract Background Amplicon-based mycobiome analysis has the potential to identify all fungal species within a sample and hence could provide a valuable diagnostic assay for use in clinical mycology settings. In the last decade, the mycobiome has been increasingly characterised by targeting the internal transcribed spacer (ITS) regions. Although ITS targets give broad coverage and high sensitivity, they fail to provide accurate quantitation as the copy number of ITS regions in fungal genomes is highly variable even within species. To address these issues, this study aimed to develop a novel NGS fungal diagnostic assay using an alternative amplicon target. Methods Novel universal primers were designed to amplify a highly diverse single copy and uniformly sized DNA target (Tef1) to enable mycobiome analysis on the Illumina iSeq100 which is a low cost, small footprint and simple to use next-generation sequencing platform. To enable automated analysis and rapid results, a streamlined bioinformatics workflow and sequence database were also developed. Sequencing of mock fungal communities was performed to compare the Tef1 assay and established ITS1-based method. The assay was further evaluated using clinical respiratory samples and the feasibility of using internal spike-in quantitative controls was assessed. Results The Tef1 assay successfully identified and quantified Aspergillus, Penicillium, Candida, Cryptococcus, Rhizopus, Fusarium and Lomentospora species from mock communities. The Tef1 assay was also capable of differentiating closely related species such as A. fumigatus and A. fischeri. In addition, it outperformed ITS1 at identifying A. fumigatus and other filamentous pathogens in mixed fungal communities (in the presence or absence of background human DNA). The assay could detect as few as 2 haploid genome equivalents of A. fumigatus from clinical respiratory samples. Lastly, spike-in controls were demonstrated to enable semi-quantitation of A. fumigatus load in clinical respiratory samples using sequencing data. Conclusions This study has developed and tested a novel metabarcoding target and found the assay outperforms ITS1 at identifying clinically relevant filamentous fungi. The assay is a promising diagnostic candidate that could provide affordable NGS analysis to clinical mycology laboratories.

Abstract Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI −1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = −0.482; 95% CI,−0.813, −0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.

To harness the power of pre-trained image classification models on the extensive ImageNet dataset, early layers of pre-trained backbones have been used to capture relevant information about iris texture in the field of Iris Recognition (IR). This addresses the lack of extensive iris datasets that are required for adjusting millions of parameters in deep networks for IR. However, using intermediate layers as feature extractors introduces problems due to image alterations and aliasing effects due to down-sampling. This paper proposes an IR method that employs low-level convolutional filters from a pre-trained backbone, incorporating low-pass filters to mitigate aliasing effects resulting from both down-sampling and horizontal shifting, caused by minor head rotations during image acquisition. Furthermore, the backbone is enhanced by adapting circular padding to reduce the impact of horizontal discontinuities in the Rubber Sheet representation. The extracted features are then encoded using a novel adaptive threshold method, increasing the variability of binary iris codes, which are matched by using a single Hamming Distance without a bit-shifting process. The proposed model exhibits significantly improved performance on publicly available CASIA and IITD datasets, along with datasets containing examples of substantial pupil dilation. Finally, we tested the robustness of our proposed method against head rotations by using datasets that were modified by horizontal shifting to simulate small head rotations.

Designing Convolutional Neural Networks (CNNs) for a specific task requires not only Deep Learning expertise but also knowledge of the problem. The goal of Neuroevolution is to find CNN architectures automatically through evolution. The search time, however, is a critical problem in Neuroevolution since multiple CNNs must be trained in the evolutionary process. In this work, we propose a Neural Architecture Classifier (NAC) to avoid training architectures that would not have good performance, based on knowledge of previously trained architectures. The NAC evaluates each CNN using the CNN architecture encoding as the input. A genetic algorithm (GA) is used for evolution, and a search space with few restrictions; hence, CNN architectures can have any width, depth or shape as well as the suitable number of skip connections. We applied this methodology to solving pattern recognition problems on six well-known datasets: five subsets of the MNIST-Variations (MNIST-V) dataset and the CIFAR-10 dataset. Experiments demonstrated that integrating the NAC in the GA reduces the search time by up to 44% compared to conventional GAs. Additionally, the architectures found by evolution with our classifier achieved a better performance (4.6% on average) than those found by traditional evolution. Our results improved the state-of-the-art by 5.2% (0.33% error reduction) on the most difficult dataset of the MNIST-V (MRDBI), and an average of 4% (0.24% error reduction) on the MNIST-V datasets. Additionally, our results on CIFAR-10 are close to those of the state-of-the-art but with significantly reduced search time. The application of a classifier can be relevant and useful not only for genetic algorithms, but also for other evolutionary algorithms.

Abstract Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling schistosomiasis for over four decades, but despite that it is ineffective against juvenile worms and size and taste issues with its pharmaceutical forms impose challenges for treating school-aged children. It is also important to note that PZQ resistant strains can be generated in laboratory conditions and observed in the field, hence its extensive use in mass drug administration programs raises concerns about resistance, highlighting the need to search for new schistosomicidal drugs. Schistosomes survival relies on the redox enzyme thioredoxin glutathione reductase (TGR), a validated target for the development of new anti-schistosomal drugs. Here we report a high-throughput fragment screening campaign of 768 compounds against S. mansoni TGR (SmTGR) using X-ray crystallography. We observed 49 binding events involving 35 distinct molecular fragments which were found to be distributed across 16 binding sites. Most sites are described for the first time within SmTGR, a noteworthy exception being the “doorstop pocket” near the NADPH binding site. We have compared results from hotspots and pocket druggability analysis of SmTGR with the experimental binding sites found in this work, with our results indicating only limited coincidence between experimental and computational results. Finally, we discuss that binding sites at the doorstop/NADPH binding site and in the SmTGR dimer interface, should be prioritized for developing SmTGR inhibitors as new antischistosomal drugs.

Abstract Phosphorus (P) is the key nutrient thought to limit primary productivity on geological timescales, and hence P bioavailability exerted a major influence on Earth’s surface oxygenation dynamics through the Precambrian, with ensuing implications for biological evolution. Here, we document highly elevated P contents in non-glacial Ediacaran (635–541 Ma) iron formations from Northwestern China, with P dominantly occurring as carbonate fluorapatite formed during early diagenesis. These analyses, in combination with marine sediment P contents and phosphorite abundance data, point to a state change in oceanic P concentrations during the Ediacaran, which we attribute to enhanced recycling from marine sediments under redox-stratified conditions. Subsequent elevated rates of primary productivity and organic carbon production may have sustained the contemporaneous first appearance of complex deep marine habitats, and would have increased the extent and stability of surface water oxygen concentrations, leading to conditions conducive to the subsequent evolution of more complex animals.

This paper identifies the narrow interpretation of the constructive alignment model (Biggs, 1996), which has permeated higher education programs internationally, as a key source for this continuing disconnect between higher education and the needs of employers, students and society. Furthermore, a systematic framework extending the traditional constructive alignment model is proposed to enable curriculum development, implementation and assurance decisions to be made with explicit reference to the needs of a variety of stakeholders. This paper is relevant for educators involved in professional degree programs, professional employers and university administrators.

Objectives This study sought to explore whether generalised joint hypermobility (GJH, a common marker of variant connective tissue) was a risk factor for self-reported non-recovery from COVID-19 infection.Design Prospective observational study.Setting COVID Symptom Study Biobank (https://cssbiobank.com/) UKParticipants Participants were surveyed in August 2022. 3064 (81.4%) reported at least one infection with COVID-19. These individuals self-reported on recovery and completed a self-report questionnaire to detect GJH (Hakim and Grahame 5-part questionnaire, 5PQ).Main outcome measures The primary outcome was the presence of self-reported non-recovery from COVID-19 infection at the time of the survey. Additional outcomes included scores on 5PQ and self-reported fatigue level (Chalder Fatigue Scale).Results The presence of GJH was not specifically associated with reported COVID-19 infection risk per se. However, it was significantly associated with non-recovery from COVID-19 (OR 1.43 (95% CI 1.20 to 1.70)). This association remained after sequential models adjusting for age, sex, ethnic group, education level and index of multiple deprivation (OR 1.33 (95% CI 1.10 to 1.61)) and further adjustment for vaccination status and number of vaccinations (OR 1.33 (95% CI 1.10 to 1.60)). Additionally, including in a model adjusting for all covariates, hypermobility significantly predicted higher fatigue levels (B=0.95, SE=0.25, t=3.77, SE, p=0.002). Fatigue levels mediated the link between GJH and non-recovery from COVID-19 (estimate of indirect effect=0.18, 95% bootstrapped CI 0.08 to 0.29).Conclusions Individuals with GJH were approximately 30% more likely not to have recovered fully from COVID-19 infection at the time of the questionnaire, and this predicted the fatigue level. This observation is clinically important through its potential impact for understanding and identifying sub-phenotypes of long COVID for screening and personalised targeted interventions. More generally, greater awareness of GJH and its extra-articular associations is needed for effective patient stratification and implementation of personalised medicine.

Background Cemiplimab (Libtayo®), a human monoclonal immunoglobulin G4 antibody to the programmed cell death-1 receptor, is approved for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC), who are not candidates for curative surgery or curative radiation, using an every-3-weeks (Q3W) dosing interval. Pharmacokinetic modeling indicated that Ctrough of extended intravenous dosing of 600 mg every 4 weeks (Q4W) would be comparable to the approved intravenous dosage of 350 mg Q3W. We examined the efficacy, pharmacokinetics, and safety of cemiplimab dosed Q4W.Methods In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review.Results Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0–39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n=14) achieving complete response and 40% (n=25) achieving partial response. The most common treatment-emergent adverse events were diarrhea, pruritus, and fatigue.Conclusions Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit−risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen.

Abstract Controls on Mesoproterozoic ocean redox heterogeneity, and links to nutrient cycling and oxygenation feedbacks, remain poorly resolved. Here, we report ocean redox and phosphorus cycling across two high-resolution sections from the ~1.4 Ga Xiamaling Formation, North China Craton. In the lower section, fluctuations in trade wind intensity regulated the spatial extent of a ferruginous oxygen minimum zone, promoting phosphorus drawdown and persistent oligotrophic conditions. In the upper section, high but variable continental chemical weathering rates led to periodic fluctuations between highly and weakly euxinic conditions, promoting phosphorus recycling and persistent eutrophication. Biogeochemical modeling demonstrates how changes in geographical location relative to global atmospheric circulation cells could have driven these temporal changes in regional ocean biogeochemistry. Our approach suggests that much of the ocean redox heterogeneity apparent in the Mesoproterozoic record can be explained by climate forcing at individual locations, rather than specific events or step-changes in global oceanic redox conditions.

The Illawarra plum (IP) is native to Australia and has been used as a bush food for centuries. With rich phytochemicals and natural pigments, IP has the potential to be an added ingredient to improve the physicochemical properties of food, including yoghurt. This study prepared dried IP powders through vacuum drying (VD) and freeze drying (FD), produced extracts from these dried powders, and fortified them into Greek-style set yoghurt. The changes in colour, pH, titratable acidity (TA), syneresis, total soluble solids (TS), and phytochemicals were measured throughout a chilled storage period of 28 days. The results showed that FD and FD extract could provide a stable, distinct pink colour to yoghurt. IP powders and their extracts improved TS content and, thus, the consistency of yoghurt. Compared to the control, VD, FD, and FD extract of IP did not significantly affect the level of acidity or syneresis after 28 days of chilled storage. Yoghurt fortified with FD and FD extract had the greatest level of phenolics, anthocyanins, and radical scavenging antioxidant activities. This study revealed that IP powders and their extracts can positively improve the physicochemical properties of Greek-style set yoghurt. FD powder is recommended over its extract to fortify this yoghurt, as it can be cost-effectively prepared by freeze drying and then grinding the fresh fruit into powder. Future studies are needed to evaluate other variables in yoghurt preparation, including the concentration of IP and strains of yoghurt culture. Further, the consumer perception of sensory quality and acceptability of yoghurt fortified with FD IP powder should be investigated.

Background: There is now substantial evidence that language interventions delivered to small groups can be effective for improving language skills and hence strengthening the foundation for formal schooling. However, there are remaining challenges when delivering such interventions in naturalistic environments at scale. Method: We reflect on three randomised trials designed to evaluate the impact of an early years language programme, prior to the implementation of a large effectiveness trial, delivered in partnership with speech and language professionals. We consider findings within a framework from implementation science. Results: We found that, in contrast to policy-led interventions for reading and mathematics, language interventions are not prioritised in mainstream settings. Aside from this, other obstacles to delivery were the time taken to prepare and to timetable sessions, lack of communication about the requirements of delivery and the need for language screening. Crucial to success was the support from the class teacher of teaching assistants delivering the intervention. However, feedback was largely positive from most stakeholders, and the intervention was found to have a positive impact on children's language with preliminary evidence for effects on behaviour and on reading comprehension. Conclusions: While many educators recognise the importance of language for communication, the benefits of oral language interventions are only recently becoming prioritised by policy-makers. We propose that challenges to successful delivery and adoption of evidence-based language interventions in mainstream settings can be remedied through better communication with stakeholders and collaboration between researchers and professional colleagues including senior leaders, teachers, teaching assistants, speech and language therapists and psychologists. It is imperative to take account of issues of implementation when designing an intervention and to do this successfully is a multidisciplinary enterprise.

Standardisation is a procedure used by Awarding Organisations to maximise marking reliability, by teaching examiners to consistently judge scripts using a mark scheme. However, research shows that people are better at comparing two objects than judging each object individually. Consequently, Oxford, Cambridge and RSA (OCR, a UK awarding organisation) proposed investigating a new procedure, involving ranking essays, where essay quality is judged in comparison to other essays. This study investigated the marking reliability yielded by traditional standardisation and ranking standardisation. The study entailed a marking experiment followed by examiners completing a questionnaire. In the control condition live procedures were emulated as authentically as possible within the confines of a study. The experimental condition involved ranking the quality of essays from the best to the worst and then assigning marks. After each standardisation procedure the examiners marked 50 essays from an AS History unit. All participants experienced both procedures, and marking reliability was measured. Additionally, the participants' questionnaire responses were analysed to gain an insight into examiners' experience. It is concluded that the Ranking Procedure is unsuitable for use in public examinations in its current form. The Traditional Procedure produced statistically significantly more reliable marking, whilst the Ranking Procedure involved a complex decision-making process. However, the Ranking Procedure produced slightly more reliable marking at the extremities of the mark range, where previous research has shown that marking tends to be less reliable.

Abstract Background Early language difficulties are associated with poor school readiness and can impact lifelong attainment. The quality of the early home language environment is linked to language outcomes. However, few home-based language interventions have sufficient evidence of effectiveness in improving preschool children’s language abilities. This study reports the first stage in the evaluation of a theory-based programme, Talking Together (developed and delivered by BHT Early Education and Training) given over 6 weeks to families in the home setting. We aimed to test the feasibility and acceptability of delivering Talking Together in the Better Start Bradford community prior to a definitive trial, using a two-armed randomised controlled feasibility study. Methods Families from a single site within the Better Start Bradford reach area were randomly allocated (1:1) to the Talking Together intervention or a wait list control group. Child language and parent-level outcome measures were administered before randomisation (baseline), pre-intervention (pre-test), 2 months post-intervention start (post-test), and 6 months post-intervention start (follow-up). Routine monitoring data from families and practitioners were also collected for eligibility, consent, protocol adherence, and attrition rates. Descriptive statistics on the feasibility and reliability of potential outcome measures were analysed alongside qualitative feedback on trial design acceptability. Pre-defined progression-to-trial criteria using a traffic light system were assessed using routine monitoring data. Results Two-hundred and twenty-two families were assessed for eligibility; of these, 164 were eligible. A total of 102 families consented and were randomised (intervention: 52, waitlist control: 50); 68% of families completed outcome measures at 6-month follow-up. Recruitment (eligibility and consent) reached ‘green’ progression criteria; however, adherence reached ‘amber’ and attrition reached ‘red’ criteria. Child- and parent-level data were successfully measured, and the Oxford-CDI was identified as a suitable primary outcome measure for a definitive trial. Qualitative data not only indicated that the procedures were largely acceptable to practitioners and families but also identified areas for improvement in adherence and attrition rates. Conclusions Referral rates indicate that Talking Together is a much-needed service and was positively received by the community. A full trial is feasible with adaptations to improve adherence and reduce attrition. Trial registration ISRCTN registry ISRCTN13251954. Retrospectively registered 21 February 2019

Abstract Whilst most individuals with SARS-CoV-2 infection have relatively mild disease, managed in the community, it was noted early in the pandemic that individuals with cardiovascular risk factors were more likely to experience severe acute disease, requiring hospitalisation. As the pandemic has progressed, increasing concern has also developed over long symptom duration in many individuals after SARS-CoV-2 infection, including among the majority who are managed acutely in the community. Risk factors for long symptom duration, including biological variables, are still poorly defined. Here, we examine post-illness metabolomic profiles, using nuclear magnetic resonance (Nightingale Health Oyj), and gut-microbiome profiles, using shotgun metagenomic sequencing (Illumina Inc), in 2561 community-dwelling participants with SARS-CoV-2. Illness duration ranged from asymptomatic (n = 307) to Post-COVID Syndrome (n = 180), and included participants with prolonged non-COVID-19 illnesses (n = 287). We also assess a pre-established metabolomic biomarker score, previously associated with hospitalisation for both acute pneumonia and severe acute COVID-19 illness, for its association with illness duration. We found an atherogenic-dyslipidaemic metabolic profile, including biomarkers such as fatty acids and cholesterol, was associated with longer duration of illness, both in individuals with and without SARS-CoV-2 infection. Greater values of a pre-existing metabolomic biomarker score also associated with longer duration of illness, regardless of SARS-CoV-2 infection. We found no association between illness duration and gut microbiome profiles in convalescence. This highlights the potential role of cardiometabolic dysfunction in relation to the experience of long duration symptoms after symptoms of acute infection, both COVID-19 as well as other illnesses.

Light-sheet microscopy has made possible the 3D imaging of both fixed and live biological tissue, with samples as large as the entire mouse brain. However, segmentation and quantification of that data remains a time-consuming manual undertaking. Machine learning methods promise the possibility of automating this process. This study seeks to advance the performance of prior models through optimizing transfer learning. We fine-tuned the existing TrailMap model using expert-labeled data from noradrenergic axonal structures in the mouse brain. By changing the cross-entropy weights and using augmentation, we demonstrate a generally improved adjusted F1-score over using the originally trained TrailMap model within our test datasets.

Background Preschool language skills and language delay predict academic and socioemotional outcomes. Children from deprived environments are at a higher risk of language delay, and both minority ethnic and bilingual children can experience a gap in language skills at school entry. However, research that examines late talking (preschool language delay) in an ethnically diverse, bilingual, deprived environment at age 2 is scarce.Methods Data from Born in Bradford’s Better Start birth cohort were used to identify rates of late talking (≤10th percentile on the Oxford-Communicative Development Inventory: Short) in 2-year-old children within an ethnically diverse, predominantly bilingual, deprived UK region (N=712). The relations between known demographic, maternal, distal and proximal child risk factors, and language skills and language delay were tested using hierarchical linear and logistic regression.Results A total of 24.86% of children were classified as late talkers. Maternal demographic factors (ethnicity, born in UK, education, financial security, employment, household size, age) predicted 3.12% of the variance in children’s expressive vocabulary. Adding maternal language factors (maternal native language, home languages) and perinatal factors (birth weight, gestation) to the model predicted 3.76% of the variance. Adding distal child factors (child sex, child age) predicted 11.06%, and adding proximal child factors (receptive vocabulary, hearing concerns) predicted 49.51%. Significant risk factors for late talking were male sex (OR 2.07, 95% CI 1.38 to 3.09), receptive vocabulary delay (OR 8.40, 95% CI 4.99 to 14.11) and parent-reported hearing concerns (OR 7.85, 95% CI 1.90 to 32.47). Protective factors were increased household size (OR 0.85, 95% CI 0.77 to 0.95) and age (OR 0.82, 95% CI 0.70 to 0.96).Conclusions Almost one in four children living in an ethnically diverse and deprived UK area have early language delay. Demographic factors explained little variance in early vocabulary, whereas proximal child factors held more predictive value. The results indicate further research on early language delay is warranted for vulnerable groups.

Objective:. The objective of the study was to compare the use of ordinal scales and interval scales for capturing surgical competency information for general surgeons performing 3 complex trauma procedures. Background:. Surgical performance assessment is typically captured using nonparametric data (eg, checklists) that do not support inferential analyses. Interval scales support parametric analyses that are essential for determining competency. We compared assessment outcomes for surgeons performing 3 complex trauma procedures using ordinal and interval scales. Methods:. All participants were board-certified or eligible general surgeons. Each participant was assessed by an experienced trauma surgeon while performing 3 trauma procedures on cadavers. All assessors completed a rigorous assessment certification process. We calculated descriptive statistics to examine the differences between interval (parametric) and ordinal (nonparametric) outcomes. Results:. Ordinal scales overestimated competence in up to 100% of the participants and did not identify specific performance gaps. Interval scales provided more granularity and identified specific capability gaps. Conclusions:. Imprecise instrumentation conveys a false sense of competence and deprives surgeons of opportunities to close capability gaps. Measuring discrete procedural components with interval scales provides a more precise measurement of surgical competency.

Purpose: To assess the incidence of adverse cerebrovascular events following shoulder arthroscopy in the beach-chair position when compared with the lateral position. Methods: Records of 5 shoulder surgeons were searched using Current Procedural Technology codes to identify patients who underwent arthroscopic shoulder surgery in both the beach-chair and lateral positions between 2015 and 2020. Using both Current Procedural Technology codes for cerebrovascular accident (CVA) imaging as well as the International Classification of Diseases, Tenth Revision, codes for CVA and late neurologic sequela, patient charts were analyzed in the 30-day postoperative period. The anesthesiology record also was queried for data regarding the blood pressure management intraoperatively, recording mean arterial pressures (MAPs), and vasopressor administration. Patient demographics, comorbidities, and complications were compared between the 2 cohorts using the Student 2-tailed t-test for continuous variables and χ2 analysis for categorical variables. Significance was set at P < .05. Results: There were 711 patients included in the analysis, with 471 in the beach-chair cohort and 240 in the lateral cohort. Baseline demographics were similar between groups, except for age and American Society of Anesthesiologists physical status classification, with the lateral group being significantly younger (P < .001) and lower American Society of Anesthesiologists physical status classification (P = .001) than the beach-chair group. Mean body mass index, history of CVA, transient ischemic attack, hypertension, and peripheral vascular disease were not significantly different. There were no documented CVAs in either cohort. There was no significant difference in the number of postoperative radiologic scans to evaluate for CVA (P = .77) or neurologic sequelae (P = .48) between groups. The beach-chair cohort had fewer instances of MAP

Background In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.Methods Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child’s immunisation booklet containing records of birth weight and serial weights in the first year.Results 2373 children participated, 52% girls, median age (IQR), 10 years (8–13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms ‘wheeze in the last 12 months’; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and ‘trouble breathing’ 3.18 (95% CI 2.27 to 4.45), p

ABSTRACTPulmonary infections caused by the mould pathogen Aspergillus fumigatus are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.

Abstract Background A. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which are responsible for stimulation of immune responses. Study of the dynamics of allergen production by fungi may lead to insights into how allergens are presented to the immune system. Methods Expression of 17 A. fumigatus allergen genes was examined in response to various culture conditions and stimuli as well as in the presence of macrophages in order to mimic conditions encountered in the lung. Results Expression of 14/17 allergen genes was strongly induced by oxidative stress caused by hydrogen peroxide (Asp f 1, -2, -4, -5, -6, -7, -8, -10, -13, -17 and -18, all >10-fold and Asp f 11, -12, and -22, 5-10-fold) and 16/17 allergen genes were repressed in the presence of cAMP. The 4 protease allergen genes (Asp f -5, -10, -13 and -18) were expressed at very low levels compared to the comparator (β-tubulin) under all other conditions examined. Mild heat shock, anoxia, lipid and presence of macrophages did not result in coordinated changes in allergen gene expression. Growth on lipid as sole carbon source contributed to the moderate induction of most of the allergen genes. Heat shock (37°C > 42°C) caused moderate repression in 11/17 genes (Asp f 1, -2, -4, -5, -6, -9, -10, -13, -17, -18 and -23) (2- to 9-fold), which was mostly evident for Asp f 1 and -9 (~9-fold). Anaerobic stress led to moderate induction of 13/17 genes (1.1 to 4-fold) with one, Asp f 8 induced over 10-fold when grown under mineral oil. Complex changes were seen in gene expression during co-culture of A. fumigatus with macrophages. Conclusions Remarkable coordination of allergen gene expression in response to a specific condition (oxidative stress or the presence of cAMP) has been observed, implying that a single biological stimulus may play a role in allergen gene regulation. Interdiction of a putative allergen expression induction signalling pathway might provide a novel therapy for treatment of fungal allergy.