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In response to the exponential growth in the prevalence of autism in Ireland and 95% of all children availing of the universal free pre-school scheme, AsIAm delivered a continuing professional development (CPD) programme, to 311 adult learners. The paper reports on a multi-method evaluation of the impact of the programme on early childhood teachers' capacity to effectively include and support autistic children. The findings underline the importance of government investment in lifelong learning and the potential of a focused CPD programme to transform both participants' professional lives and the experiences they provide for the children in early learning and care services. Recommendations for future policy development are also suggested.

Abstract In 2019, we faced a pandemic due to the coronavirus disease (COVID-19), with millions of confirmed cases and reported deaths. Even in recovered patients, symptoms can be persistent over weeks, termed Post-COVID. In addition to common symptoms of fatigue, muscle weakness, and cognitive impairments, visual impairments have been reported. Automatic classification of COVID and Post-COVID is researched based on blood samples and radiation-based procedures, among others. However, a symptom-oriented assessment for visual impairments is still missing. Thus, we propose a Virtual Reality environment in which stereoscopic stimuli are displayed to test the patient’s stereopsis performance. While performing the visual tasks, the eyes’ gaze and pupil diameter are recorded. We collected data from 15 controls and 20 Post-COVID patients in a study. Therefrom, we extracted features of three main data groups, stereopsis performance, pupil diameter, and gaze behavior, and trained various classifiers. The Random Forest classifier achieved the best result with 71% accuracy. The recorded data support the classification result showing worse stereopsis performance and eye movement alterations in Post-COVID. There are limitations in the study design, comprising a small sample size and the use of an eye tracking system.

Abstract A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Using a synthetic gut bacterial community, we aimed to study the role of individual members in community assembly, identify putative keystone species and test their influence across different environments. Single-species dropout experiments reveal that bacterial strain relationships strongly vary not only in different regions of the murine gut, but also across several standard culture media. Mechanisms involved in environment-dependent keystone functions in vitro include exclusive access to polysaccharides as well as bacteriocin production. Further, Bacteroides caecimuris and Blautia coccoides are found to play keystone roles in gnotobiotic mice by impacting community composition, the metabolic landscape and inflammatory responses. In summary, the presented study highlights the strong interdependency between bacterial community ecology and the biotic and abiotic environment. These results question the concept of universally valid keystone species in the gastrointestinal ecosystem and underline the context-dependency of both, keystone functions and bacterial interaction networks.

Abstract Background High-risk surveillance for patients with Li-Fraumeni syndrome (LFS) has shown a stage shift and improved overall survival, but is demanding. Our objective was to evaluate surveillance adherence in a population of patients with LFS presenting for high-risk care. Methods A retrospective analysis of surveillance adherence of adult patients with LFS at a single institution was performed. Adherence was defined by the duration from initial University of Virginia (UVA) LFS clinic visit to the time of first missed surveillance test. Two-sample t-tests and ANOVA tests were used to identify factors associated with duration of adherence. Results A total of 42 patients were evaluated in the UVA LFS clinic between 2017 and 2021. Of these, 21 patients met inclusion criteria. At the time of review, 6 patients (29%) were up to date with high-risk surveillance recommendations. The mean duration of adherence was 17 months. Female sex was found to be associated with longer duration of adherence (mean 21 mo vs. 3.5 mo for males, p = 0.02). A personal history or active diagnosis of cancer was also associated with increased adherence (p = 0.02). However, neither age (p = 0.89), geography (p = 0.84), or known family history of LFS (p = 0.08) were associated with duration of adherence. Conclusion Female sex as well as a personal history of cancer were associated with longer duration of adherence to recommended high-risk surveillance among patients with LFS. Identification of barriers to surveillance will be essential moving forward to increase adherence and promote early detection of cancer, thereby reducing the morbidity and mortality of LFS.

Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Abstract Background We report on a study of a facilitated interactive group learning approach, through Collaborative Implementation Groups (CIGs), established to enhance capacity for equity‐sensitive evaluation of healthcare services to inform local decision‐making: (1) What was the experience of participants of the CIGs? (2) How was knowledge mobilisation achieved? (3) What are the key elements that enhance the process of coproducing equity‐sensitive evaluations? Methods A thematic analysis of qualitative data obtained from focus group (FG) discussions and semistructured interviews exploring the experiences of participants. All FGs included representation of participants from different projects across the programme. Interviews were conducted with a member from each of the teams participating in the first cohort after their final workshop. Results We identified four themes to illustrate how the approach to delivering intensive and facilitated training supported equity‐sensitive evaluations of local healthcare services: (1) Creating the setting for coproduction and knowledge mobilisation; (2) establishing a common purpose, meaning and language for reducing health inequalities; (3) making connections and brokering relationships and (4) challenging and transforming the role of evaluation. Conclusion We report on the implementation of a practical example of engaged scholarship, where teams of healthcare staff were supported with resources, interactive training and methodological advice to evaluate their own services, enabling organisations to assemble timely practical and relevant evidence that could feed directly into local decision‐making. By encouraging mixed teams of practitioners, commissioners, patients, the public and researchers to work together to coproduce their evaluations, the programme also aimed to systematise health equity into service change. The findings of our study illustrate that the approach to delivering training gave participants the tools and confidence to address their organisation's stated aims of reducing health inequalities, coproduce evaluations of their local services and mobilise knowledge from a range of stakeholders. Patient or Public Contribution The research question was developed collaboratively with researchers, partner organisations and public advisers (PAs). PAs were involved in meetings to agree on the focus of this research and to plan the analysis. N. T. is a PA and coauthor, contributing to the interpretation of findings and drafting of the paper.

We propose that Frantz Fanon’s analysis of language develops an immanent critique of Maurice Merleau-Ponty’s phenomenology. Fanon transforms the phenomenological method to account for the Black speaking subjects’ experience through a sociogenic account of language. First, while the French colonial language has a robust diachronic dimension, the language of the colonized, Creole, is relegated to a synchrony without diachrony, as the historical past is erased. Second, while French metropolitan intersubjectivity is modelled on harmonious reciprocity and reflects continuity between the family and the state, relations between dominant and subjugated speaking subjects employ paternalism and primitivism that reinforce coloniality. We develop the notion of a racialized and historicized language-schema to capture Fanon’s analysis and envisage future critical phenomenologies of language.

Anna Höller,1,* Bich Doan Nguyen-Sträuli,1,2,* Heike Frauchiger-Heuer,1,* Alexander Ring1– 3,* 1Department of Gynecology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; 2Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; 3Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland*These authors contributed equally to this workCorrespondence: Heike Frauchiger-Heuer, Tel +41 44 255 42 37, Email Heike.Frauchiger-Heuer@usz.ch; Alexander Ring, Tel +41 76 327 8287, Email Alexander.Ring@usz.chAbstract: Luminal breast cancers are hormone receptor (estrogen and/or progesterone) positive that are further divided into HER2-negative luminal A and HER2-positive luminal B subtypes. According to currently accepted convention, they represent the most common subtypes of breast cancer, accounting for approximately 70% of cases. Biomarkers play a critical role in the functional characterization, prognostication, and therapeutic prediction, rendering them indispensable for the clinical management of invasive breast cancer. Traditional biomarkers include clinicopathological parameters, which are increasingly extended by genetic and other molecular markers, enabling the comprehensive characterization of patients with luminal breast cancer. Liquid biopsies capturing and analyzing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging technologies that envision personalized management through precision oncology. This article reviews key biomarkers in luminal breast cancer and ongoing developments.Keywords: breast cancer, luminal A and B, biomarker, circulating tumor cells, circulating tumor DNA

Abstract Pulmonary fibrosis is a devastating disease, in which fibrotic tissue progressively replaces lung alveolar structure, resulting in chronic respiratory failure. Alveolar type II cells act as epithelial stem cells, being able to transdifferentiate into alveolar type I cells, which mediate gas exchange, thus contributing to lung homeostasis and repair after damage. Impaired epithelial transdifferentiation is emerging as a major pathogenetic mechanism driving both onset and progression of fibrosis in the lung. Here, we show that lung endothelial cells secrete angiocrine factors that regulate alveolar cell differentiation. Specifically, we build on our previous data on the anti-fibrotic microRNA-200c and identify the Vascular Endothelial Growth Factor receptor 1, also named Flt1, as its main functional target in endothelial cells. Endothelial-specific knockout of Flt1 reproduces the anti-fibrotic effect of microRNA-200c against pulmonary fibrosis and results in the secretion of a pool of soluble factors and matrix components able to promote epithelial transdifferentiation in a paracrine manner. Collectively, these data indicate the existence of a complex endothelial-epithelial paracrine crosstalk in vitro and in vivo and position lung endothelial cells as a relevant therapeutic target in the fight against pulmonary fibrosis.

Background We analyzed association between viewing two-dimensional computed tomography (2D CT) images in addition to radiographs with radial head treatment recommendations after accounting for patient and surgeon factors in a survey-based experiment. Methods One hundred and fifty-four surgeons reviewed 15 patient scenarios with terrible triad fracture dislocations of the elbow. Surgeons were randomized to view either radiographs only or radiographs and 2D CT images. The scenarios randomized patient age, hand dominance, and occupation. For each scenario, surgeons were asked if they would recommend fixation or arthroplasty of the radial head. Multi-level logistic regression analysis identified variables associated with radial head treatment recommendations. Results Reviewing 2D CT images in addition to radiographs had no statistical association with treatment recommendations. A higher likelihood of recommending prosthetic arthroplasty was associated with older patient age, patient occupation not requiring manual labor, surgeon practice location in the United States, practicing for five years or less, and the subspecialties “trauma” and “shoulder and elbow.” Conclusions The results of this study suggest that in terrible triad injuries, the imaging appearance of radial head fractures has no measurable influence on treatment recommendations. Personal surgeon factors and patient demographic characteristics may have a larger role in surgical decision making. Level of evidence Level III, therapeutic case-control study.

Abstract Background The Glasgow Sensory Questionnaire (GSQ) gives insight into sensory processing differences (hypo- and hyper-sensitivity across modalities), which is a clinically defining characteristic of autism spectrum disorder (ASD). Because there is no validated German version of this instrument, this study aimed at validating the German GSQ. Further, a replication of the GSQ’s sensory processing differences was intended. Methods University students of Technische Universität or Universitätsklinikum in Dresden, Germany, were recruited via email distribution or the university homepage and 297 German-speaking students completed the online survey, comprising the German GSQ, Autism-Spectrum Quotient (AQ) and Symptom-Checklist (SCL-90). For validation of the German GSQ, confirmatory factor analyses followed by exploratory factor analyses were applied. Results The German GSQ has moderate to low validity, good to acceptable reliability, and a different internal structure from the original GSQ. Replicating the sensory processing differences in students with higher and lower AQ was not successful. Conclusions Results indicate that the GSQ, developed especially for individuals with ASD, is less informative for the general population if there are not enough individuals with higher AQ scores in the sample.

Mechanical site preparation (MSP) is deliberate soil disturbance which is undertaken to improve the conditions for forest regeneration. Disc trenching and mounding are the dominant MSP practices currently used in Sweden and Finland. In this paper, the impacts of MSP on the soil, water quality, greenhouse gas (GHG) emissions and ground vegetation of mineral soil sites in Sweden and Finland are reviewed. The practices considered are patch scarification, mounding, inverting, disc trenching, and ploughing, which together represent a wide range of soil disturbance intensity. The environmental effects of MSP in this region have not been studied extensively. The environmental impact of MSP derives from the process of creating microsites which involves horizontal and/or vertical redistribution of soil and soil mixing. This typically affects decomposition, element circulation and leaching, vegetation coverage and uptake of nutrients and water, and possibly erosion and sediment exports. Following disc trenching or mounding the effects on GHG emissions appear to be minor over the first two years. For a few years after disc trenching concentrations in soil water collected below ridges are higher than that below furrows for some elements (e.g., NO3-, NH4+, Mg2+, and total or dissolved organic C). The physical and chemical effects of ploughing remain detectable for several decades. There is little evidence about how the effects of forestry activities in upland areas on soil-water chemistry are transferred to adjacent surface water bodies, including what role streamside discharge areas play. MSP increases the tree biomass C store and may increase the total ecosystem C store. The impact of MSP on the cover and abundance of ground vegetation species depends on the composition of the original plant community, MSP intensity, and the establishment rate of different species. Species cover generally seems to decline for late succession understory species, while pioneer and ruderal species can benefit from the microsites created. Areas containing lichens which are used for reindeer forage require special consideration. More research is needed on the environmental effects of MSP, particularly regarding its long-term effects. Further efforts should be made to develop efficient site-preparation practices which better balance the disturbance intensity with what is needed for successful regeneration.

IntroductionIn this study, we investigated the impact of cardiorespiratory fitness (CRF), quantified as peak oxygen consumption (VO2peak), on the relationship between work rates (WR) at the aerobic threshold (AerT) and the point of maximal fat oxidation rate (Fatmax).MethodsA total of 761 untrained adults aged 41–68 completed a one-minute incremental exercise test on a cycle ergometer, using breath-by-breath gas analysis to determine VO2peak, AerT, and Fatmax. AerT was determined using automatic and visual detection methods, and Fatmax was determined using indirect calorimetry. Participants were categorized into CRF-groups: low (

Proteomics is the identification, detection and quantification of proteins within a biological sample. The complete set of proteins expressed by an organism is known as the proteome. The availability of new high-throughput proteomic technologies, such as Olink Proteomic Proximity Extension Assay (PEA) technology has enabled detailed investigation of the circulating proteome in large-scale epidemiological studies. In particular, the Olink® Target 96 inflammatory panel allows the measurement of 92 circulating inflammatory proteins. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1991-1992 and has followed these women, their partners, and their offspring ever since. In this data note, we describe the newly-released proteomic data available in ALSPAC. Ninety-two proteins were analysed in 9000 blood plasma samples using the Olink® Target 96 inflammatory panel. Samples were derived from 2968 fasted mothers (mean age 47.5; Focus on Mothers 1 (FOM1)), 3005 non-fasted offspring at age 9 (Focus@9) and 3027 fasted offspring at age 24 (Focus@24). Post sample filtering, 1834 offspring have data at both timepoints and 1119 of those have data from their mother available. We performed quality control analyses using a standardised data processing workflow (metaboprep) to produce a filtered dataset of 8983 samples for researchers to use in future analyses. Initial validation analyses indicate that IL-6 measured using the Olink® Target 96 inflammatory panel is highly correlated with IL-6 previously measured by clinical chemistry (Pearson’s correlation = 0.77) and we are able to reproduce the reported positive correlation between body mass index (BMI) and IL-6. The pre-processing and validation analyses indicate a rich proteomic dataset to further characterise the role of inflammation in health and disease.

BackgroundDepersonalisation-Derealisation Disorder (DDD) is a distressing mental health condition which causes individuals to have a sense of 'unreality' or detachment about themselves and/or the world around them. DDD is chronically under-researched, and as a result, under-diagnosed, with a population prevalence of about 1%. In systematic reviews, Cognitive Behavioural Therapy (CBT) has been found to be the only intervention with significant clinical impact on alleviating the symptoms of DDD. However, previous studies have suffered from small sample sizes, reliance on expert clinicians to provide therapy and narrow population demographics. This feasibility randomised controlled trial aims to provide more robust evidence for the treatment efficacy of CBT in DDD.MethodsThe study aims to recruit 40 participants from two NHS trusts, 20 per arm from two community Mental Health NHS services in London. The intervention group will receive 12-24 individual CBT sessions over a 6-month period from CBT therapists following specialist training for DDD. The control group will receive Treatment as Usual. We will assess the feasibility of a future RCT through measuring the acceptability of the intervention, and assessing our ability to recruit, retain and randomise participants. We will calculate the correlation of scores on the Cambridge Depersonalisation Scale, its baseline standard deviation, assess the magnitude/direction of change and characterise the uncertainty in the outcome scores and the probability that the results have been obtained by chance.DiscussionThe outputs of this trial will guide whether a definite RCT is feasible and acceptable, for both the clinician and participant.Trial registrationThe ISRCTN registration number is ISRCTN97686121(https://doi.org/10.1186/ISRCTN97686121).

Abstract Effective monitoring of wildlife species requires thorough planning and development of survey programmes that can address management and conservation objectives. Decisions about monitoring programmes include where to survey, survey design and how much effort to allocate at survey sites are typically predicated on limited budgets and available resources. When the scope of inference requires monitoring on a broad spatial scale, predictions of habitat distribution or suitability may be useful for identifying potential survey sites. We focused on a threatened but widely distributed shorebird, the piping plover (Charadrius melodus), which is actively monitored across some, but not all of its range. Our objective was to use piping plover habitat distribution maps, which vary annually, to assess the effectiveness of multiple monitoring programme scenarios and their associated costs. In the breeding range, efforts to improve productivity for species of conservation concern often focus on improving probabilities of nest survival. Consequently, collecting adequate nesting data is crucial for obtaining accurate and precise estimates of nest survival and for evaluating the effectiveness of management actions. By simulating the nest monitoring process, we evaluated how much area, where and how often to survey each site when estimating nest survival and detecting effects of potential management actions. As expected, precision increased and bias decreased around nest survival estimates with greater survey coverage and nest visit frequency. We also identified monitoring programmes with negative net values where survey costs outweighed statistical benefits. Although we applied our simulation framework to evaluate nest monitoring designs for piping plovers, it could be extended to assess whether different monitoring programmes can detect changes in the distribution of other species or occupancy of habitats over time.

OBJECTIVES Educational interventions with proven effectiveness to reduce medication prescribing errors are currently lacking. Our objective was to implement and assess the effectiveness of a curriculum to reduce medication prescribing errors on a surgery service. METHODS This was a prospective observational cohort study at a Canadian academic hospital without an electronic order entry system. A pharmacist-led medication prescribing curriculum for surgery residents was developed and implemented over 2 days (2 h/day) in July 2019. Thirteen (76%) out of 17 surgery residents contributed pre-implementation data, while 13 (81%) out of 16 surgery residents contributed post-implementation data. Medication prescribing errors were tracked for 12 months pre-implementation and 6 months post-implementation. Errors were classified as prescription writing (PW) or decision making (DM). RESULTS There were a total of 1050 medication prescribing errors made in the pre-implementation period with 615 (59%) PW errors and 435 (41%) DM. There were a mean of 87.5 (SD = 14.6) total medication prescribing errors per month in the pre-implementation period with 51.3 (11.9) PW and 36.3 (6.0) DM errors. There were a total of 472 medication prescribing errors made in the post-implementation period with 260 (55%) PW and 212 (45%) DM errors. There were a mean of 78.7 (10.3) total medication prescribing errors per month in the post-implementation period with 43.3 (9.5) PW and 35.3 (4.2) DM errors. In the first quarter of the academic year, there were significantly fewer mean total errors per month post-implementation versus pre-implementation (77.7(12.7) versus 107.3(8.1); P = .035), with significantly fewer PW errors per month (40.7(13.2) versus 68.7(9.3); P = .046) and no difference in DM errors per month (37.0(2.0) versus 38.7(5.7); P = .671). There were no differences noted in the second quarter of the academic year. CONCLUSION Medication prescribing errors occurred from PW and DM. Medication prescribing curriculum decreased PW errors; however, a continued education program is warranted as the effect diminished over time.

IntroductionSalmonella Enteritidis and S. Typhimurium are the two most clinically important zoonotic Salmonella serovars and vaccination of breeding and laying hens affords effective Salmonella control. The use of live vaccines has proven beneficial for a number of reasons, including ease of application, protection from the first day of life onwards and initiation of a strong local immune response. Live vaccines can be applied in the drinking water from the first day of life onwards, but some rearers choose to wait until the end of the first week to ensure sufficient water consumption. However, this practice leaves the birds unprotected during the crucial first week of life, where they are most susceptible to colonization by field strains. The aim of this study was to determine if successful vaccine uptake is achieved when layer pullets are vaccinated as early as day one.MethodsThree pullet flocks were vaccinated at 1, 2, 3 or 5 days-of-age with AviPro™ Salmonella DUO, a live vaccine containing attenuated strains of S. Enteritidis and S. Typhimurium (Elanco Animal Health, Cuxhaven, Germany). The vaccine was administered via the drinking water following manufacturer’s instructions. Two days post-vaccination, 10 birds per flock were culled and caecal and liver samples taken, along with two pools of faeces per flock. Levels of vaccine strains were determined by quantitative and qualitative bacteriology.ResultsVaccine strains were detected in all birds from all age groups indicating successful uptake of the vaccine. Levels of the S. Enteritidis vaccine were higher than levels of the S. Typhimurium vaccine, with the latter frequently only detectable following enrichment. There was an inverse correlation between age and caecal levels of vaccines, with the highest numbers seen in birds vaccinated at 1-day-of-age. Interestingly, S. Enteritidis vaccine strain levels in liver samples were highest when birds were vaccinated at 5 days-of-age.DiscussionThese results show that successful uptake of both vaccine strains was evident in all age groups. The earlier the chicks were vaccinated, the higher the vaccine levels in caecal contents. We therefore recommend vaccination of pullets as early as practicably possible to ensure protection against exposure to field strains.

Abstract. Objective:. To compare performance between linear regression (LR) and artificial neural network (ANN) models in estimating 9-month patient-reported outcomes (PROs) after upper extremity fractures using various subsets of early mental, social, and physical health variables. Methods:. We studied 734 patients with isolated shoulder, elbow, or wrist fracture who completed demographics, mental and social health measures, and PROs at baseline, 2–4 weeks, and 6–9 months postinjury. PROs included 3 measures of capability (QuickDASH, PROMIS-UE-PF, PROMIS-PI) and one of pain intensity. We developed ANN and LR models with various selections of variables (20, 23, 29, 34, and 54) to estimate 9-month PROs using a training subset (70%) and internally validated them using another subset (15%). We assessed the accuracy of the estimated value being within one MCID of the actual 9-month PRO value in a test subset (15%). Results:. ANNs outperformed LR in estimating 9-month outcomes in all models except the 20-variable model for capability measures and 20-variable and 23-variable models for pain intensity. The accuracy of ANN versus LR in the primary model (29-variable) was 83% versus 73% (Quick-DASH), 68% versus 65% (PROMIS-UE-PF), 66% versus 62% (PROMIS-PI), and 78% versus 65% (pain intensity). Mental and social health factors contributed most to the estimations. Conclusion:. ANNs outperform LR in estimating 9-month PROs, particularly with a larger number of variables. Given the otherwise relatively comparable performance, aspects such as practicality of collecting greater sets of variables, nonparametric distribution, and presence of nonlinear correlations should be considered when deciding between these statistical methods.

Abstract Background Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first‐line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self‐administrable devices, especially in community settings. Different commercial AAIs have been authorized to be marketed in Europe. For an AAI to be efficacious, a rapid adrenaline delivery in patients, including those who are overweight or obese, resulting in an optimal cardiovascular (CV) response, is a key feature. AAIs are designed to achieve this requirement, which is reflected in their differing functional properties such as primary container selection, drug delivery mechanism (cartridge‐or syringe‐based), needle length, needle gauge, and adrenaline dose (150 μg, 300 μg, or 500 μg). However, the differences in functional properties across these devices may play a critical role in achieving these requirements as well as the differences in ergonomics in the handling of these devices. The purpose of this review Considering the dynamic pharmacokinetic/pharmacodynamic (PK/PD) profiles of different AAIs marketed in Europe and their effect on adrenaline delivery, the expert panel, also serving as author for this paper have carried out a detailed analysis of the PK/PD profiles of four AAIs, namely, Anapen, Emerade, EpiPen, and Jext, to delineate the adrenaline delivery and their subsequent physiological effects on the backdrop of device characteristics, dose strength, and the skin‐to‐muscle distances of the participants.

IntroductionThe COVID-19 epidemic has provided opportunity to study the impact of a well-defined severe illness on the development of a depressive episode and the associated sense of loneliness and lack of meaning in life.Materials and MethodsThe aim of the study was to assess the occurrence of a reactive depressive episode, the severity of depression, a sense of loneliness and meaning in life in subjects who approximately a year earlier than the date of the study had suffered from a pulmonary form of SARS-CoV-2 infection with radiologically documented interstitial lesions of the lungs, requiring and not requiring hospitalization compared to people who did not develop the disease as a result of infection with that virus. The study included 63 subjects hospitalized for pulmonary lesions, 67 not hospitalized and 60 healthy controls. The severity of depressive symptoms was measured using a Polish-language standardized version of the Beck Depression Inventory, a sense of loneliness using the De Jong Gierveld Loneliness Scale, and a sense of meaning in life using the Life Attitude Profile-Revised.ResultsThe frequency of depression and its severity were found to be the highest in hospitalized patients compared to those treated at home and healthy people. A significant difference in the frequency of depression and its severity between outpatients and healthy people was also observed. The feeling of loneliness turned out to be greatest in the group of hospitalized people. Also, the severity of loneliness was found to be higher in the outpatient compared to the control group. The sense of meaning in life reached its lowest level among hospitalized patients, was moderately reduced in the outpatient group, and typical of the Polish population in the control group.DiscussionBoth pulmonary SARS-CoV-2 infection and hospitalization have been shown to be a risk factor for depression, increased feeling of loneliness and a reduced sense of meaning in life. The effect of trauma and the presence of depression can be the explanation for the increased sense of loneliness after the illness and the partial breakdown of the lifeline manifested by a decrease in the sense of meaning in life.

Pseudospin symmetry (PSS) is a relativistic dynamical symmetry connected with the lower component of the Dirac spinor. Here, we investigate the conservation and breaking of PSS in the single-nucleon resonant states, as an example, using Green's function method that provides a novel way to precisely describe not only the resonant energies and widths but also the spacial density distributions for both narrow and wide resonances. The PSS conservation and breaking are perfectly displayed in the evolution of resonant parameters and density distributions with the potential depth: In the PSS limit, i.e., when the attractive scalar and repulsive vector potentials have the same magnitude but opposite sign, PSS is exactly conserved with strictly the same energy and width between the PS partners as well as identical density distributions of the lower components. As the potential depth increases, the PSS is broken gradually with energy and width splittings and a phase shift in the density distributions.

ABSTRACTRecent global and regional assessments of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) show that Nature’s Contributions to People (NCP) are under an alarming threat due to the continuing loss of biodiversity. These assessments call for increasing conservation efforts and a more sustainable use of biodiversity to enhance the chances of halting biodiversity loss and reversing current trends. One of the strategies to achieve change is to mainstream biodiversity into sectoral policies. Mainstreaming, a concept that can be traced back to the Brundtland report, promotes the integration of the environment into political, societal, and economic planning and decision-making. Based on the review of key studies undertaken during the regional assessment for Europe and Central Asia, we develop a stepwise approach to analyze the current status of mainstreaming of biodiversity and NCP. The approach can be used both for policy design purposes and diagnostic evaluations. It demonstrates that mainstreaming has the potential to improve the conservation and sustainable use of biodiversity as well as the sustained provision of NCP. However, based on the status of implementation across Europe and Central Asia, we conclude that mainstreaming needs to be pursued and implemented in a stronger and more systematic way. The results of our assessment provide important input to national strategies and policies but also to the ongoing process of the Conference of the Parties to the Convention on Biological Diversity while developing the post-2020 global biodiversity framework.

We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P

Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.

Abstract Introduction Social prescribing has become an important feature of the UK primary care offer. However, there remains limited evidence on how best to implement and deliver social prescribing programmes to maximise effectiveness and long-term sustainability. Aim To explore social prescribing practices and experience of implementing social prescribing programmes across National Institute for Health and Social Care Research (NIHR) Collaborative Leadership for Applied Health and Care Research (CLAHRC) North West Coast (NWC) and NIHR Applied Research Collaboration (ARC) NWC region to identify key learning points that can be applied to other settings. Method We held a learning exchange workshop attended by practitioners and Public Advisors who had been involved in implementing and evaluating eight different social prescribing programmes with the support of NIHR CLAHRC NWC. We followed this with an online survey of social prescribing practice and priorities within the NIHR ARC NWC area. We used the findings from the workshop and survey to develop an initial model of the elements needed to successfully implement and sustain a working social prescribing programme. Findings We identified three core essential elements for a successful social prescribing programme: a personalised approach; meaningful service-user and community involvement; and whole systems working. These core elements need to be supported with adequate resources in the form of continuity of funding and adequate community resources to refer people to, capacity building and appropriate evaluation. Conclusion We were able to use a learning exchange workshop to both facilitate learning between practitioners and begin the process of identifying the ingredients needed for a successful social prescribing programme, which may be built on with further research.

Abstract Incorporating species distributions into conservation planning has traditionally involved long-term representations of habitat use where temporal variation is averaged to reveal habitats that are most suitable across time. Advances in remote sensing and analytical tools have allowed for the integration of dynamic processes into species distribution modeling. Our objective was to develop a spatiotemporal model of breeding habitat use for a federally threatened shorebird (piping plover, Charadrius melodus). Piping plovers are an ideal candidate species for dynamic habitat models because they depend on habitat created and maintained by variable hydrological processes and disturbance. We integrated a 20-year (2000–2019) nesting dataset with volunteer-collected sightings (eBird) using point process modeling. Our analysis incorporated spatiotemporal autocorrelation, differential observation processes within data streams, and dynamic environmental covariates. We evaluated the transferability of this model in space and time and the contribution of the eBird dataset. eBird data provided more complete spatial coverage in our study system than nest monitoring data. Patterns of observed breeding density depended on both dynamic (e.g., surface water levels) and long-term (e.g., proximity to permanent wetland basins) environmental processes. Our study provides a framework for quantifying dynamic spatiotemporal patterns of breeding density. This assessment can be iteratively updated with additional data to improve conservation and management efforts, because reducing temporal variability to average patterns of use may cause a loss in precision for such actions.

Abstract Background Social distancing restrictions to manage the COVID-19 pandemic were put in place from March 2020 in the United Kingdom (UK), with those classed as “highly clinically vulnerable” advised to shield entirely and remain at home. However, personal risk perception has been shown to comprise of various elements beyond those outlined in the national pandemic guidance. It is unclear whether those deemed COVID-19 vulnerable identified as high-risk to COVID-19 and thus complied with the relevant advice. The aim of this research is to explore the perception of risk in catching and spreading COVID-19, amongst individuals from individual households, and vulnerable groups in a region of the UK. Methods Two individual, semi-structured interviews were conducted, four-weeks apart, with adults living in households in the Liverpool City Region. At the follow-up interview, participants were given the option of using photo-elicitation to guide the discussion. Reflexive thematic analysis was employed to conceptualise themes. The qualitative analysis was underpinned with symbolic interactionism. Results Twenty-seven participants (13:14 males:females, and 20 with a vulnerable risk factor to COVID-19) completed a baseline interview, and 15 of these completed a follow-up interview four-weeks later. Following thematic analysis, two overarching themes were conceptualised, with subthemes discussed: theme 1) Confusion and trust in the risk prevention guidance; and theme 2) Navigating risk: compliance and non-compliance with public health guidance. Conclusion Participants developed their own understanding of COVID-19 risk perception through personal experience and comparison with others around them, irrespective of vulnerability status. COVID-19 guidance was not complied with as intended by the government, and at times even rejected due to lack of trust. The format in which future pandemic guidance is conveyed must be carefully considered, and take into account individuals’ experiences that may lead to non-compliance. The findings from our study can inform future public health policy and interventions for COVID-19 and future pandemics.

Background: The modern multimodal treatment of malignant tumors has increased disease-specific survival and decreased the burden of tumor-associated complications. The main focus of palliative surgery is not based primarily on quantitative success parameters of tumor response but is instead mainly on the question of quality of life. Aim: The current study was conducted to analyze the clinical and oncological outcomes of palliative patients with soft tissue sarcoma. Design: Of 309 patients with extra-abdominal high-grade soft tissue sarcoma treated between August 2012 and December 2014, our retrospective analysis revealed 33 palliative patients for this study. All patients were evaluated and managed by a multidisciplinary team with expertise and experience in sarcoma treatment. The survival analysis was made using the Kaplan?Meier method. Results: The main sarcoma symptoms were pain (27.3%) and ulcerated tumors or shortly before ulceration (24.2%). Thirteen patients (39.4%) were operated on with negative margins, 15 (45.5%) with positive margins, 2 with tumor debulking (6.1%), and 3 patients (9.1%) were treated only with palliative hyperthermic isolated limb perfusion. Ten pedicle flaps were performed after sarcoma resection. The median operation time was 85 minutes (range, 37?216 minutes). The median hospitalization stay was 9.5 days (range, 3?27 days). No patients died during hospitalization. Twelve-month disease-free survival was 48.5% (95% confidence interval: 45.4?51.6). Conclusions: Palliative surgery of metastatic or advanced soft tissue sarcoma can improve the wound care and quality of life. Closed noninfected wounds enable further treatment options, such as chemotherapy, immunotherapy, and radiotherapy. This surgery should be considered during the discussion on interdisciplinary tumor boards.

Whilst SARS-CoV-2 mRNA vaccines have demonstrated efficacy in reducing infection severity, research has shown that SARS-CoV-2 infection is associated with new autoantibodies. Whether this would also be observed during mRNA vaccination is unclear. Here, the authors use an autoantibody screening platform to monitor autoantibody responses in a diverse cohort during vaccination.