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The Varved Sediments Database (VARDA) was launched in 2020 and aimed to establish a community database for annually resolved chronological archives with their associated high-resolution proxy records. This resource would support reproducibility through accessible data for the paleoclimate and modelling communities. In this paper, VARDA has been extended by a dataset of European tephra geochemical data and metadata to enable the synchronisation of varve records during the Last Glacial–Interglacial Transition (LGIT; here defined as 25 to 8 ka; Beckett et al., 2022). Geochemical data from 49 known individual tephra layers across 19 lake records have been included, with Lago di Grande Monticchio being the single biggest contributor of geochemical data with 28 tephra layers. The Vedde Ash and Laacher See tephra are the most common layers found in six different records. This highlights the potential of refining the absolute age estimates for these tephra layers using varve chronologies and for synchronising regional paleoclimate archives. This is the first stage in a 5-year plan funded by the Past Global Changes (PAGES) Data Stewardship Scholarship to incorporate a global dataset of tephra geochemical data into varve records. Further stages of this project will focus on different regions and timescales. Data collated for this project are available open access at https://doi.org/10.5880/fidgeo.2023.015 (Beckett et al., 2022).

Summary: Background: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). Aim: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. Methods: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. Findings: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). Conclusion: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.

The polarisation of attitudes towards dyslexia appears to be contingent upon the awareness of the implications of adopting a medical model to interpreting dyslexia (as a medical 'condition') or applying an educational overlay, based upon difficulties in certain areas, to interpreting and making provision for those with dyslexia. Specifically, it underscores the difficulties dyslexics have in reading and the comprehension of what has been read. Furthermore, it accentuates the approaches taken in the 1980s and the turn of the century to dyslexia was, for these interviewees, unfitting. However, it raises other questions about whether the current practice is suited to the needs of those with dyslexia, or whether a universal offer is made, regardless of specific need. In the wake of this research, three emergent themes occur, dyslexia and stigmatisation, the impact of stigmatisation and poorly suited provision upon self-esteem and the stress this generates. As key practitioner points, this disquisition underlines the need to tailor provision for inclusive education based upon the needs of the individual with dyslexia. It further illumines the stress of unsuitable provision, manifesting the imperative nature of adequate training and resourcing for dyslexia.

Abstract Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation. RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR included Gc, Plg, Irf7, Ifit3, Usp18, Rsad2, Blm and RT1-A2, whilst those exclusively implicated in CR responses included Alb, Apoa1, Ambp, F2, Apoh, Orm1, Mx1, Oasl2 and Rtp4. Hub genes involved in ageing but unaffected by CR included Fgg, Fga, Fgb and Serpinc1. In conclusion, this comprehensive RNA sequencing study highlights gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia.

Abstract The architectural style found in Wa and Tamale is renowned for its distinctive use of earthen construction, which features square buildings with flat roofs and circular compounds with conical thatch roofs. Recently, there has been a growing inclination towards the use of alternative construction techniques in which nontraditional materials such as cement, bitumen, and used car engine oil are utilised to render wall surfaces. These structures show how the materials and design in northern Ghana have substantially evolved. However, what forces drive the changes in cob construction in this region? Furthermore, how might these changes impact the preservation of cultural heritage in Ghana? To explore the factors that contribute to the departure from traditional earthen building methods that rely on local materials, this study employs a constructivist research approach. Participants in a survey that informed this study revealed that they struggled to access building materials to construct their houses. While most of the people who responded to the survey have resided in buildings constructed with a mixture of beini and dawadawa, they hesitate to use plant-based biostabilisers in new constructions. Factors that hinder the ongoing construction and preservation of earthen buildings include shifting cultural and social norms, environmental changes, difficulties accessing local building resources, flood risks, regular maintenance requirements, and societal influences. Thus, this study concludes that if communities are empowered to take ownership and recognise the value of their cultural heritage, they are likely to be increasingly aware and appreciative of their architectural heritage. Thus, their local heritage will be preserved.

Periparturient dairy cows experience metabolic adaptations to prepare for increased nutrient requirements of the fetus and the onset of lactation. Adaptations include increased peripheral tissue insulin resistance, which can be evaluated experimentally using intravenous glucose tolerance tests (IVGTT). The objective of this study was to determine if prepartum skeletal muscle reserves and supplementation of branched-chain volatile fatty acids (BCVFA) in the prepartum period affected blood glucose, β-hydroxybutyrate (BHB), and insulin concentrations 2 wk prepartum and 1 wk postpartum utilizing an IVGTT. At 42 d before expected calving (BEC), the longissimus dorsi muscle depth was measured from an ultrasound image, and based on muscle depth, cows were assigned to either the high muscle (HM; >4.6 cm, n = 17) or low muscle (LM; ≤4.6 cm, n = 17) group. Cows were randomly assigned to either the branched-chain volatile fatty acid (BCVFA) treatment (fed as 39.1 g/d isobutyrate product; 19.4 g/d isovalerate product; 19.6 g/d 2-methylbutyrate product, all on a DM basis) or control (73.0 g/d soyhull pellets on a DM basis) treatment, which were top-dressed daily. Assignment to muscle group and treatment resulted in a 2 × 2 factorial design and the following 4 combinations: HM-CON (n = 7), HM-BCVFA (n = 10), LM-CON (n = 9), and LM-BCVFA (n = 8). On 14 d BEC and 7 DIM an IVGTT was performed following a 1 h fasting period. Baseline blood samples were taken −15 and −5 min before dextrose administration (250 mg/kg BW); blood was then collected at 12 time points over a 3-h time period. Skeletal muscle reserves had no impact on glucose or insulin response across the IVGTT period, whereas BCVFA supplementation increased glucose area under the curve (AUC) in the prepartum period but had no effect in the postpartum period. Prepartum glucose and insulin AUC were higher than the postpartum glucose and insulin AUC. Findings indicate that muscle reserves in the prepartum period do not affect insulin and glucose clearance in periparturient dairy cows, reflecting no differences in insulin sensitivity in response to IVGTT. Changes observed in glucose and insulin AUC between pre- and postpartum IVGTT reflect normal metabolic adaptations to increased energetic requirements of dairy cows between late gestation and early lactation.

Abstract Background Despite high disease burden and heightened suicide risk associated with psychosis, psychosis education is lacking in healthcare curricula, potentially hindering students’ willingness, and confidence to provide psychosis care as future healthcare professionals. This study aimed to co-design and content validate psychosis care assessment material for medical, pharmacy, nursing, and occupational therapy curricula. Methods A nominal group technique (NGT) meeting was conducted to generate and rank ideas among people with lived/living experience of mental illness. Prioritised ideas were used to create simulated role-play scenarios for each discipline, by discipline experts. The developed scenarios underwent content validation by content experts, whereby the content validity index was computed for relevance and clarity. Results The four highest ranked ideas based on rank scores and accumulated rank score sums were selected during the NGT meeting and used to guide the development of four role-play scenarios focusing on antipsychotic medication side effects, suicide risk, paranoia and delusions, and visual hallucinations. Discipline experts created scenario outlines and rubrics for each selected idea. Content validity indices of all items were deemed satisfactory, ranging from 0.8 to 1. Written feedback for each role-play scenario was considered and scenarios/rubrics were modified accordingly. Conclusion Overall, this study provides a framework for partnering with mental health stakeholders to co-design and validate psychosis care assessment material for healthcare curricula. Through the integral contribution of people with lived/living experience and clinicians, authentic scenarios which reflect real-life practice have been developed. Future research is required to evaluate the newly developed materials in educational setting.

ABSTRACT: Periparturient dairy cattle undergo physiological adaptations to support fetal growth and colostrum synthesis in late gestation and milk production in early lactation. To support energy and protein demands, dairy cattle mobilize body tissue reserves. The objective of this study was to determine the effects of prepartum skeletal muscle reserves and supplementation of branched-chain volatile fatty acids (BCVFA) on body composition measurements, metabolic markers related to health, protein, and energy status, and subsequent milk yield in multiparous dairy cows. Skeletal muscle reserves were assessed by 3 ultrasounds of the longissimus dorsi muscle depth (LDD) measured 42 d before expected calving, and cows (n = 48) were assigned to either high muscle (HM; >4.6 cm) or low muscle (LM; ≤4.6 cm) groups. Cows were then randomly assigned to either control (CON) of soyhull pellets (80 g/d) or BCVFA treatment, which contained isobutyrate (40 g/d), isovalerate (20 g/d), and 2-methylbutyrate (20 g/d) calcium salt products. Treatments were top dressed from 42 d before expected calving until parturition, resulting in 4 combinations of muscle groups and treatments: HM-CON (n = 13), HM-BCVFA (n = 13), LM-CON (n = 11), and LM-BCVFA (n = 11). Measurements of the LDD, BW, and BCS were taken on the following days relative to calving: −42, −35, −21, −7, 0, 7, 14, 21, 28. Weekly blood samples were taken to measure glucose, BHB, and insulin concentrations, and 5 of the blood sample time points were used to determine 3-methylhistidine and creatinine blood concentrations. Milk yield was recorded daily for the first 28 d of lactation, and samples were taken from both milkings once a week for the first 4 wk to determine components. The statistical model included the fixed effects of treatment, group, time, and their interactions, and the random effect of cow nested within group and treatment. Prepartum muscle mobilization varied between muscle groups, as LM cows accreted muscle prepartum, and HM cows mobilized muscle. The HM cows had higher milk fat, protein, lactose, and energy-corrected milk yields. The BCVFA supplementation tended to increase blood glucose concentrations both prepartum and postpartum and decreased milk urea nitrogen concentrations. Greater prepartum skeletal muscle reserves improve productivity of early-lactation cows, likely due to differences in muscle mobilization, and BCVFA supplementation improves glucose dynamics during the transition period, which may improve the metabolic health of the periparturient dairy cow.

Summary: Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.

Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

IntroductionContemporary data and knowledge management and exploration are challenging due to regular releases, updates, and different types and formats. In the food and nutrition domain, solutions for integrating such data and knowledge with respect to the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles are still lacking.MethodsTo address this issue, we have developed a data and knowledge management system called NutriBase, which supports the compilation of a food composition database and its integration with evidence-based knowledge. This research is a novel contribution because it allows for the interconnection and complementation of food composition data with knowledge and takes what has been done in the past a step further by enabling the integration of knowledge. NutriBase focuses on two important challenges; data (semantic) harmonization by using the existing ontologies, and reducing missing data by semi-automatic data imputation made from conflating with existing databases.Results and discussionThe developed web-based tool is highly modifiable and can be further customized to meet national or international requirements. It can help create and maintain the quality management system needed to assure data quality. Newly generated data and knowledge can continuously be added, as interoperability with other systems is enabled. The tool is intended for use by domain experts, food compilers, and researchers who can add and edit food-relevant data and knowledge. However, the tool is also accessible to food manufacturers, who can regularly update information about their products and thus give consumers access to current data. Moreover, the traceability of the data and knowledge provenance allows the compilation of a trustworthy management system. The system is designed to allow easy integration of data from different sources, which enables data borrowing and reduction of missing data. In this paper, the feasibility of NutriBase is demonstrated on Slovenian food-related data and knowledge, which is further linked with international resources. Outputs such as matched food components and food classifications have been integrated into semantic resources that are currently under development in various international projects.

We present a Python package called Modular Petri Net Assembly Toolkit (MPAT) that empowers users to easily create large-scale, modular Petri Nets for various spatial configurations, including extensive spatial grids or those derived from shapefiles, augmented with heterogeneous information layers. Petri Nets are powerful discrete event system modeling tools in computational biology and engineering. However, their utility for automated construction of large-scale spatial models has been limited by gaps in existing modeling software packages. MPAT addresses this gap by supporting the development of modular Petri Net models with flexible spatial geometries.

Combining key elements from the learning tools of reflection, feedback and debriefing into a single reflective event is a novel concept. This powerful combination amalgamates into a tool useful in experiential learning. Linking the three concepts in a way that combines self-reflection in a debriefing framework, powered by trusted peer feedback resulted in a new teaching tool. It was piloted within the clinical setting of the primary health care (PHC) clinics in the Saldanha Bay sub-district in South Africa among final (6th) year undergraduate medical students of the University of Cape Town. This sub-district is a peri-urban community and encompasses a district health care system with less resources in both human and infrastructure than in an urban area. Being intentional and analytical as to optimal use of every resource not only impacts the students but also alleviates the pressure on clinician supervisors of activities. Pairing students alleviates the pressure of the insufficient number of consultation rooms for solo consultations and the pressure on the single supervising clinician when the consultations are conducted simultaneously. Using this tool at the end of the session facilitates the reflection and experiential learning of both the students individually. Self-reports indicated this tool kept both students engaged throughout all consultations and facilitated peer learning Alternating between being the doctor and the observer and knowing what roles entailed, the students never felt victimised in the reflection and feedback on their performance. And individually they developed their self-reflection and providing feedback as life skills.

PURPOSECanadian radiation oncology professionals have a strong history of involvement in global oncology initiatives worldwide. This pan-Canadian survey-based study was conducted to determine the current level of engagement of Canadian radiation oncologists (ROs) and medical physicists (MPs) in global oncology initiatives and broaden the development of these activities.MATERIALS AND METHODSThis was a cross-sectional study. The survey was designed to characterize current levels of engagement of Canadian ROs and MPs in global oncology initiatives. The survey was open from March 2019 to April 2020. It was disseminated to all Canadian Association of Radiation Oncology and Canadian Organization of Medical Physicists members with two subsequent email reminders.RESULTSSurvey responses were received from 40 (93%) of the 43 Canadian cancer treatment centers that offer radiotherapy. At least one RO responded at 34 centers (79%) and one MP from 34 centers (79%) with some overlap. A response was received from a total of 93 participants, 47 ROs and 46 MPs. Of all survey participants, 58% reported some experience with global oncology. Nineteen percent of the participants surveyed were currently directly involved in short- or long-term projects, more than half of which have opportunity for additional staff involvement. The projects spanned 26 countries in South America, Africa, and Asia. Quality improvement and capacity building accounted for 27% and 20% of initiatives, respectively. The most common area of engagement was in direct treatment care, accounting for 56% of the projects.CONCLUSIONThis study demonstrates the landscape of involvement of Canadian ROs and MPs in global oncology initiatives. The study also highlights areas of opportunity for broadening international participation and collaboration as it relates to global oncology for Canadian radiation oncology professionals.

Despite increasing recognition of children's right to have a say about matters that affect them (Article 12, United Nations Convention on the Rights of the Child), this right is often denied in the context of child abuse research. This article explores the ways in which ethical decision-making can contribute to the denial of this right and the negative implications of this at both an individual and societal level.Ethical decision-making that stymies the conduct of abuse-focused research with children is usually justified with reference to protecting participants from risk of harm. Whilst in no way suggesting that this is not a critical consideration, the authors question the simplistic and deterministic ways in which this can be understood within ethical decision-making, and the unnecessarily risk-averse decisions that can ensue.Sharing examples from their cumulative 30 years' experience of engaging children and young people in abuse-focused research, the authors stress the need for a more holistic, nuanced and dynamic approach to assessing and managing risk of harm. This would consider risks of both inclusion and exclusion. Understanding that risk and harm are neither static nor universally experienced concepts, it would recognise the implausibility of the ‘do no harm’ guarantees often expected of social researchers. Instead, informed by rights-respecting and trauma-informed perspectives, it would focus on holistically promoting participant wellbeing in, and through, research. Key to this is permitting, and supporting, researchers to exercise contextually-informed, collaborative decision-making in the field; something the authors share their emerging practice framework for.