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BACKGROUND: There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants. METHOD: Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately. RESULTS: The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those

01 januari 2023, Item does not contain fulltext, PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.

01 juli 2023, Item does not contain fulltext, Jansen-de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of PPM1D. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease-causing variants in PPM1D leading to JdVS. Clinical data were provided by treating physicians and/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75 years (range 8 months to 62 years). Four families document autosomal dominant transmission, and 32/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48 months of age. Common manifestations included global developmental delay (35/36, 97%), hypotonia (25/34, 74%), short stature (14/33, 42%), constipation (22/31, 71%), and cyclic vomiting (6/35, 17%). Distinctive personality traits include a hypersocial affect (21/31, 68%) and moderate-to-severe anxiety (18/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in PPM1D with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation.

01 januari 2023, Item does not contain fulltext, PURPOSE: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder. METHODS: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature. RESULTS: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss. CONCLUSION: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.

Importance: Understanding which children in the general population are at greatest risk of poor functional outcomes could improve early screening and intervention strategies. Objective: To investigate the odds of poor outcomes in emerging adulthood (ages 17 to 20 years) for children with different mental health trajectories at ages 9 to 13 years. Design, Setting, and Participants: Growing Up in Ireland is a longitudinal, nationally representative population-based cohort study. Data collection began in August 2007 and was repeated most recently in September 2018. All results were weighted to account for sampling bias and attrition and were adjusted for socioeconomic factors. Data analysis took place from October 2022 to April 2023. Exposure: Four latent classes captured variation in mental health in children aged 9 and 13 years, based on the parent-completed Strengths and Difficulties Questionnaire. Classes included no psychopathology, internalizing, externalizing, and high (comorbid) psychopathology. Those who remained in the same class from ages 9 to 13 years were included. Main Outcomes and Measures: Poor functional outcomes in emerging adulthood were measured at approximate ages 17 years (range, 16 to 18 years) and 20 years (range, 19 to 21 years). Outcomes included poor mental health, poor physical health, social isolation, heavy substance use, frequent health service use, poor subjective well-being, and adverse educational/economic outcomes. Results: Of 5141 included participants, 2618 (50.9%) were male. A total of 3726 (72.5%) were classed as having no childhood psychopathology, 1025 (19.9%) as having persistent externalizing psychopathology, 243 (4.7%) as having persistent internalizing psychopathology, and 147 (2.9%) as having persistent high psychopathology. Having any childhood psychopathology was associated with poorer functional outcomes in emerging adulthood. The internalizing group had elevated odds of most outcomes except for heavy substance

CONTEXT: Delirium is a serious neurocognitive syndrome which is highly prevalent in people approaching the end of life. Existing trials of interventions to prevent or treat delirium in adults receiving palliative care report heterogeneous outcomes. OBJECTIVES: To undertake an international consensus process to develop a core outcome set for trials of interventions, designed to prevent and/or treat delirium, for adults receiving palliative care. METHODS: The core outcome set development process included a systematic review, qualitative interviews, modified Delphi method and virtual consensus meetings using nominal group technique (Registration http://www.comet-initiative.org/studies/details/796). Participants included family members, clinicians, and researchers with experience of delirium in palliative care. RESULTS: Forty outcomes were generated from the systematic review and interviews informing the Delphi Round one survey. The international Delphi panel comprised 92 participants including clinicians (n = 71, 77%), researchers (n = 13, 14%), and family members (n = 8, 9%). Delphi Round two was completed by 77 (84%) participants from Round one. Following the consensus meetings, four outcomes were selected for the core outcome set: 1) delirium occurrence (incidence and prevalence); 2) duration of delirium until resolution defined as either no further delirium in this episode of care or death; 3) overall delirium symptom profile (agitation, delusions or hallucinations, delirium symptoms and delirium severity); 4) distress due to delirium (person with delirium, and/or family and/or carers [including healthcare professionals]). CONCLUSION: Using a rigorous consensus process, we developed a core outcome set comprising four delirium-specific outcomes for inclusion in future trials of interventions to prevent and/or treat delirium in palliative care.

This report presents results and analysis from a seasonal survey of the limnology of the 20 major lakes and tarns in the English Lake District, undertaken in April, July, October and November 2021 and January and February 2022. The survey is the eighth edition to the roughly five-yearly surveys that have been carried out since 1984.

UNLABELLED: To gain consensus on measurement methods for outcomes (delirium occurrence, severity, time to resolution, mortality, health-related quality of life [HrQoL], emotional distress including anxiety, depression, acute stress, and post-traumatic stress disorder, and cognition) of our Core Outcome Set (COS) for trials of interventions to prevent and/or treat delirium in critically ill adults. DESIGN: International consensus process. SETTING: Three virtual meetings (April 2021). PATIENTS/SUBJECTS: Critical illness survivors/family, clinicians, and researchers from six Countries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures (selected based on instrument validity, existing recommendations, and feasibility) and measurement time horizons were discussed. Participants voted on instruments and measurement timing (a priori consensus threshold ≥ 70%). Eighteen stakeholders (28% ICU survivors/family members) participated. We achieved consensus on the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist to measure delirium occurrence and delirium resolution (100%), Hospital Anxiety and Depression Scale for emotional distress (71%), and Montreal Cognitive Assessment-Blind for cognition (83%). We did not achieve consensus on EQ-5D five-level for HrQoL (69%) or its measurement at 6 months. We also did not achieve consensus on the Impact of Event Scale (IES)-Revised or IES-6 for post-traumatic stress (65%) or on measurement instruments for delirium severity incorporating delirium-related emotional distress. We were unable to gain consensus on when to commence and when to discontinue assessing for delirium occurrence and time to resolution, when to determine mortality. We gained consensus that emotional distress and cognition should be measured up to 12 months from hospital discharge. CONCLUSIONS: Consensus was reached on measurement instruments for four of seven outcomes in the COS for delirium prevention or treatment trials for critic

For many observers Australia’s approach to the threat of nuclear proliferation under the government of Prime Minister John Howard (1996–2007) was simply the product of its steadfast alignment of Australian foreign policy with that of the United States in the post-9/11 context. The Howard government’s enthusiastic support for the 2003 US-led ‘coalition of the willing’ invasion of Iraq on the basis of Baghdad’s alleged possession of ‘weapons of mass destruction’ (WMD) is taken as the most egregious example of this tendency. Yet this assumption ignores that the potential threat of nuclear proliferation had been an abiding concern for the government since it had entered office. This paper argues that there was an enduring dynamic in Australian foreign and strategic policy of perceiving a direct link between the fate of the prevailing international system and that of Australia’s own national security. To this end, the Howard government’s perception of the threat of nuclear proliferation was sensitive to trends at the global level, most particularly the strategic posture and preferences of its alliance partner, the United States. The paper demonstrates, however, that this weakened the Howard government’s ability to maintain fidelity with what had become Australia’s traditional activist diplomacy within the non-proliferation regime.

In this article the JEWELFISH Study Group members were missing in the Acknowledgements. The collaborator names are corrected in the supplementary material and the complete list is given below. In Table 1, footnote symbol ‘g’ was incorrectly written as ‘f’ in the entries Non-sitters—2 (14)g and Sitters-12 (86)g under column Onasemnogene abeparvovec of section Motor function, n (%)f. The original article has been corrected.

Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.

We previously identified a novel pathway of testosterone action via the androgen receptor (AR) in bone marrow mesenchymal precursor cells (BM-PCs) to negatively regulate fat mass and improve metabolic function in male mice. This was achieved using our PC-AR Gene Replacement mouse model in which the AR is only expressed in BM-PCs and deleted in all other tissues. We hypothesise that the markedly reduced fat mass and increased insulin sensitivity of PC-AR Gene Replacements will confer protection from diet-induced overweight and obesity. To test this, 6-week-old male PC-AR Gene Replacements and controls (WT, global-AR knockouts (KOs)) were fed a chow or high-caloric diet (HCD) for 8 or 18 weeks. Following 8 weeks (short-term) of HCD, WT and Global-ARKOs had markedly increased subcutaneous white adipose tissue (WAT) and retroperitoneal visceral adipose tissue (VAT) mass compared to chow-fed controls. In contrast, PC-AR Gene Replacements were resistant to WAT and VAT accumulation following short-term HCD feeding accompanied by fewer large adipocytes and upregulation of expression of the metabolic genes Acaca and Pnlpa2. Following long-term HCD feeding for 18 weeks, the PC-AR Gene Replacements were no longer resistant to increased WAT and VAT adiposity, however, maintained their improved whole-body insulin sensitivity with an increased rate of glucose disappearance and increased glucose uptake into subcutaneous WAT. In conclusion, the action of testosterone via the AR in BM-PCs to negatively regulate fat mass and improve metabolism confers resistance from short-term diet-induced weight gain and partial protection from long-term diet-induced obesity in male mice.

AIM: Early intervention for people experiencing first episode psychosis is a priority, and keyworkers are vital to such services. However, keyworkers' roles in addressing first episode psychosis patients' physical health are under researched. This study addresses this knowledge gap by evaluating a keyworker-mediated intervention promoting physical health among first episode psychosis patients. METHODS: The study was informed by the Medical Research Council's Framework for Complex Interventions to Improve Health. First episode psychosis participants were recruited from three Irish mental health services. The intervention was evaluated in terms of its feasibility/acceptability. RESULTS: Feasibility outcomes were mixed (recruitment rate = 24/68 [35.3%]; retention rate = 18/24 [75%]). The baseline sample was predominantly male (M:F ratio = 13:6; Med age = 25 y; IQR = 23-42 y). Common health issues among participants included overweightness/obesity (n = 11) and substance use (smoking/alcohol consumption [n = 19]). Participants' initial health priorities included exercising more (n = 10), improving diet (n = 6), weight loss (n = 7) and using various health/healthcare services. The intervention's acceptability was evidenced by the appreciation participants had for physical health keyworkers' support, as well as the healthy lifestyle, which the intervention promoted. Acceptability was somewhat compromised by a low-recruitment rate, variable linkages between keyworkers and general practitioners (GPs) and COVID-19 restrictions. CONCLUSIONS: Physical health-oriented keyworker interventions for first episode psychosis patients show promise and further evaluation of such initiatives is warranted. Future interventions should be mindful of participant recruitment challenges, strategies to enhance relationships between keyworkers and GPs, and if necessary, they should mitigate COVID-19 restrictions' impacts on care.

Urban forests are important components of societal interactions with nature. We focused on urban forest patches, a distinct and underexplored subset of the urban forest that spans land uses and ownerships, and requires silvicultural practices to address their unique biophysical characteristics and management regimes. Our goal was to elucidate multi-scalar urban forest patch governance arrangements as they translated to on-the-ground management in four urban areas (Chicago, New York City, Philadelphia, and Baltimore) within the eastern United States. A transdisciplinary knowledge co-production framework was used to guide identification of the prominent management challenge or dilemma motivating change to forest patch management in each location, and to describe the dynamic interplay of decision-making and governance processes across locations as they advanced toward desired forest conditions. A common management goal existed across all four locations: multi-age, structurally complex forests dominated by regionally native species. Ecological and social concerns affected by local context and city capacity served as starting points prompting management action and new collaborations. Disparate governance arrangements including top-down municipal resources, regional conservation facilitated by landowners, and grass-roots community-driven stewardship led to diverse support-building processes and innovative strategies that served as forces initiating and shaping new management actions. Science and iterative learning and adaptation influenced change in all locations, reinforcing new management arrangements and practices. Among the four study areas, the earliest management of urban forest patches started in the 1980 s, historically lacking embeddedness in urban forest management more broadly, and experiencing challenges with integration into existing governance infrastructure. Ultimately, new management and governance approaches to urban forest patches in all four study areas

Contains fulltext : 287910.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Efficient utilisation of surgical resources is essential when providing surgical care in low-resources settings. Countries are developing plans to scale up surgery, though insufficiently based on empirical evidence. This paper investigates the determinants of hospital efficiency in district hospitals in three African countries. METHODS: Three-month data, comprising surgical capacity indicators and volumes of major surgical procedures collected from 61 district-level hospitals in Malawi, Tanzania, and Zambia, were analysed. Data envelopment analysis was used to calculate average hospital efficiency scores (max. = 1) for each country. Quantile regression analysis was selected to estimate the relationship between surgical volume and production factors. Two-stage bootstrap regression analysis was used to estimate the determinants of hospital efficiency. RESULTS: Average hospital efficiency scores were 0.77 in Tanzania, 0.70 in Malawi and 0.41 in Zambia. Hospitals with high efficiency scores had significantly more surgical staff compared with low efficiency hospitals (DEA score<1). Hospitals that scored high on the most commonly utilised surgical capacity index were not the ones with high surgical volumes or high efficiency. The number of surgical team members, which was lowest in Zambia, was strongly, positively correlated with surgical productivity and efficiency. CONCLUSION: Hospital efficiency, combining capacity measures and surgical outputs, is a better indicator of surgical performance than capacity measures, which could be misleading if used alone for surgical planning. Investment in the surgical workforce, in particular, is critical to improving district hospital surgical productivity and efficiency.

Contains fulltext : 283148.pdf (Publisher’s version ) (Open Access), Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K(+)/H(+) exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K(+) efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial patholog

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.

Contains fulltext : 283148.pdf (Publisher’s version ) (Open Access), Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K(+)/H(+) exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K(+) efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial patholog

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Maree Clarke is a Mutti Mutti/Wemba Wemba/Boonwurrung/Yorta Yorta artist, from Mildura in northwest Victoria, Australia, now living and working in Naarm (Melbourne). With over 30 years experience as an artist, Clarke’s work focuses on new ways of telling old/ongoing stories through art-making, much of which occurs in her backyard. https://www.ngv.vic.gov.au/exhibition/maree-clarke/ https://vivienandersongallery.com/artists/maree-clarke/ Fran Edmonds is an interdisciplinary scholar who has worked extensively with Aboriginal artists, community organisations and galleries, libraries, archives and museums (GLAMs) for almost 30 years. Her work supports First Nations people to reclaim their stories from the ‘archives’. https://blogs.unimelb.edu.au/livingarchiveofaboriginalart/ https://omeka.cloud.unimelb.edu.au/livingarchivenaidoc/blog https://www.facebook.com/LivingArchiveofAboriginalArtandKnowledge

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre­diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2‐8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9‐14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13‐17 years) (OR=24.2, 95% CI: 21.2‐27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7‐1.1). Compared to other

Purpose: To compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer. Materials and methods: All centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions. Target volume receiving 95% of prescribed dose (V95%iCTVtotal) should be >99%. Robustness towards setup, range, and respiration was evaluated. The plans were recalculated on a surveillance 4DCT (sCT) acquired at fraction ten and robustness evaluation was performed to evaluate the effect of respiration and inter-fractional anatomical changes. Results: All PT and XT plans complied with V95%iCTVtotal >99% for the nominal plan and V95%iCTVtotal >97% for all respiratory and robustness scenarios. Lung and heart dose varied considerably between centres for both modalities. The difference in mean lung dose and mean heart dose between each pair of XT and PT plans was in median [range] 4.8 Gy [1.1;7.6] and 8.4 Gy [1.9;24.5], respectively. Patients B and C showed large inter-fractional anatomical changes on sCT. For patient B, the minimum V95%iCTVtotal in the worst- case robustness scenario was 45% and 94% for XT and PT, respectively. For patient C, the minimum V95%iCTVtotal was 57% and 72% for XT and PT, respectively. Patient A and D showed minor inter- fractional changes and the minimum V95%iCTVtotal was >85%. Conclusion: Large variability in dose to the lungs and heart was observed for both modalities. Inter- fractional anatomical changes led to larger target dose deterioration for XT than PT plans.

In this paper, we present a methodology for fisheries-related data that allows us to converge on a labeled image dataset by iterating over the dataset with multiple training and production loops that can exploit crowdsourcing interfaces. We present our algorithm and its results on two separate sets of image data collected using the Seabed autonomous underwater vehicle. The first dataset comprises of 2,026 completely unlabeled images, while the second consists of 21,968 images that were point annotated by experts. Our results indicate that training with a small subset and iterating on that to build a larger set of labeled data allows us to converge to a fully annotated dataset with a small number of iterations. Even in the case of a dataset labeled by experts, a single iteration of the methodology improves the labels by discovering additional complicated examples of labels associated with fish that overlap, are very small, or obscured by the contrast limitations associated with underwater imagery.

Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.

We introduce a conceptual model of the urban forest patch as a complex social-ecological system, incorporating cross-scale interactions. We developed this model through an interdisciplinary process engaging social and ecological scientists and urban land management decision makers, with a focus on temperate forest social-ecological systems. In this paper, we place the production and management of urban forest patches in historical perspective, present a conceptual model of urban forest patches within a broader regional context, and identify a series of research questions to highlight future directions for research on urban forest patches. This conceptual model identifies how spatial and temporal social-ecological drivers interact with patch-level conditions at multiple scales. Our integrative approach can provide insights into the role of social-ecological drivers in shaping forest health, biodiversity, and benefits forest patches provide to people in urban and urbanizing regions, with direct implications for decision-making to improve management outcomes.

Fire shapes ecosystems globally, including semi-arid ecosystems. In Australia, semi-arid ‘mallee’ ecosystems occur primarily across the southern part of the continent, forming an interface between the arid interior and temperate south. Mallee vegetation is characterized by short, multi-stemmed eucalypts that grow from a basal lignotuber. Fire shapes the structure and functioning of mallee ecosystems. Using the Murray Mallee region in south-eastern Australia as a case study, we examine the characteristics and role of fire, the consequences for biota, and the interaction of fire with other drivers. Wildfires in mallee ecosystems typically are large (1000s ha), burn with high severity, commonly cause top-kill of eucalypts, and create coarse-grained mosaics at a regional scale. Wildfires can occur in late spring and summer in both dry and wet years. Recovery of plant and animal communities is predictable and slow, with regeneration of eucalypts and many habitat components extending over decades. Time since the last fire strongly influences the distribution and abundance of many species and the structure of plant and animal communities. Animal species display a discrete set of generalized responses to time since fire. Systematic field studies and modeling are beginning to reveal how spatial variation in fire regimes (‘pyrodiversity’) at different scales shapes biodiversity. Pyrodiversity includes variation in the extent of post-fire habitats, the diversity of post-fire age-classes and their configuration. At regional scales, a desirable mix of fire histories for biodiversity conservation includes a combination of early, mid and late post-fire age-classes, weighted toward later seral stages that provide critical habitat for threatened species. Biodiversity is also influenced by interactions between fire and other drivers, including land clearing, rainfall, herbivory and predation. Extensive clearing for agriculture has altered the nature and impact

AIM: Studies have demonstrated that a majority of the decline in health status and functioning emerges during the first few years following the onset of psychosis. This knowledge led to the development of specialized early intervention services (EIS) targeting patients experiencing their first episode of psychosis (FEP). The central component of EIS is often assertive case management delivered by a multidisciplinary team, where an appointed key worker is responsible for coordinating treatment and delivering various psychosocial interventions to service users. The aim of this scoping review was to examine how key workers can enhance the physical health outcomes in people with FEP by addressing the factors associated with increased mortality in this population. METHODS: The scoping review framework comprised a five-stage process developed by Arksey and O'Malley. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A total of 27 studies conducted across 10 countries were analysed. These studies discussed the various ways in which key workers can mediate enhancements in the various factors contributing to the increased mortality rates in FEP patients. CONCLUSIONS: A broad range of key worker-mediated outcomes was identified, which were broadly classified into three themes: influences on lifestyle, influences on effects of psychosis and influences on organizational barriers. Our findings suggest that key workers primarily mediated the amelioration of psychosis-induced effects and the reduction of organizational barriers. Further trials of key worker interventions to enhance physical health outcomes in this cohort are warranted.

BACKGROUND: Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality. METHODS: We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs). FINDINGS: Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001) and death from breast cancer (0·67, 0·61 to 0·73; p<0·0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9·0% (95% CI 7·4 to 10·7; p<0·0001) and 10-year breast cancer mortality was reduced by 6·4% (4·9 to 7·8; p<0·0001), with a 6·5% reduction (5·0 to 8·0; p<0·0001) in all-cause mortality, and no increase in death without recurrence (0·4%, -0·3 to 1·1; p=0·35). The proportional reduction in recurrence

The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen-independent innate immunity in the upper airways can prevent the spread of respiratory virus infection to the vulnerable lower airways. Activation of TLR2, when restricted to the nasal turbinates, resulted in prompt induction of innate immune-driven antiviral responses through action of cytokines, chemokines, and cellular activity in the upper but not the lower airways. We have defined how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to 7 days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

We introduce a conceptual model of the urban forest patch as a complex social-ecological system, incorporating cross-scale interactions. We developed this model through an interdisciplinary process engaging social and ecological scientists and urban land management decision makers, with a focus on temperate forest social-ecological systems. In this paper, we place the production and management of urban forest patches in historical perspective, present a conceptual model of urban forest patches within a broader regional context, and identify a series of research questions to highlight future directions for research on urban forest patches. This conceptual model identifies how spatial and temporal social-ecological drivers interact with patch-level conditions at multiple scales. Our integrative approach can provide insights into the role of social-ecological drivers in shaping forest health, biodiversity, and benefits forest patches provide to people in urban and urbanizing regions, with direct implications for decision-making to improve management outcomes.

Abstract Previous explanations on China's counterterrorism strategy have highlighted the results of China's strategy of repression in Xinjiang, the historical antecedents and institutional foundations of its counterterrorism policies, as well as international and domestic sources of China's counterterrorism strategy. While acknowledging the importance of all these dimensions, this article draws attention to a largely neglected feature of China's counterterrorism strategy: the Chinese party-state's social engineering of Xinjiang. Building on Maoist-era practices such as the mass line and the ‘friend vs. enemy’ binary, the Communist party under Xi Jinping has integrated surveillance technologies as part of its strategy of preventive counterterrorism and ‘de-extremization’. This article argues that the Chinese party-state's embrace of modern technologies, a weak liberal tradition in China, Xi Jinping's rise to power in late 2012, and the appointment of Chen Quanguo as Xinjiang's party-secretary in 2016, provides the socio-political background for the intensification of securitization, surveillance and introduction of ‘re-education and training centres’ in Xinjiang. Surveillance technologies now complement collective, face-to-face methods of surveillance and Maoist-era techniques of mass mobilization, enabling the Chinese party-state to govern and manage the biopolitical spaces of Uyghurs with greater intensity, according to the state's precise norms. The legalization and institutionalization of ‘de-extremization’ has also led to the shift from mass ‘de-extremization’ propaganda to ‘drip-irrigation’ ideological and political re-education of individuals deemed at risk of extremism. The result is an increased capacity by the Chinese party-state to surveil and control the region, and to more effectively negate the possibility of individual resistance.

This chapter describes the challenges of a distinct aspect of ethical formalism, that of quantification, and the tension in many ethical traditions between calculation and the incalculable. Certain facets of ethical conduct can be weighed or counted, while others – such as matters of faith, mercy and trust – disrupt or evade calculation. The chapter explores this tension in the context of Sunni Islam, where adhering to religious rules in one’s personal conduct is often assumed to gain one points in a divine system of bookkeeping. Through ethnographic research in the Palestinian city of Nablus, it is argued that such divine bookkeeping can be understood as a technology of the self. Other aspects of being a good Muslim, however, break calculation apart. Ethical qualities that bear on one’s relation to God or other human beings are particularly difficult to think of in such formalistic terms. Regarding contemporary Islam, some scholars have argued that an interest in calculation stems from the rise of neo-liberal forms of capitalism. Yet attention to comparable ideas in the Christian tradition shows otherwise. St Anselm, for instance, phrased similar notions in the terms of the feudalism of his time. The chapter points instead to the repressive politics of the occupied Palestinian territories, which combine capitalist political economies with extensive security surveillance. There is an elective affinity between the microscopic scrutiny of such state surveillance and the calculated tallying of good and bad deeds.

Background: Evidence-based healthcare (EBHC) knowledge and skills are recognised as core competencies of healthcare professionals worldwide, and teaching EBHC has been widely recommended as an integral part of their training. The objective of this overview of systematic reviews (SR) was to update evidence and assess the effects of various approaches for teaching evidence-based health care (EBHC) at undergraduate (UG) and postgraduate (PG) medical education (ME) level on changes in knowledge, skills, attitudes and behaviour. Methods and findings: This is an update of an overview that was published in 2014. The process followed standard procedures specified for the previous version of the overview, with a modified search. Searches were conducted in Epistemonikos for SRs published from 1 January 2013 to 27 October 2020 with no language restrictions. We checked additional sources for ongoing and unpublished SRs. Eligibility criteria included: SRs which evaluated educational interventions for teaching EBHC compared to no intervention or a different strategy were eligible. Two reviewers independently selected SRs, extracted data and evaluated quality using standardised instrument (AMSTAR2). The effects of strategies to teach EBHC were synthesized using a narrative approach. Previously published version of this overview included 16 SR, while the updated search identified six additional SRs. We therefore included a total of 22 SRs (with a total of 141 primary studies) in this updated overview. The SRs evaluated different educational interventions of varying duration, frequency, and format to teach various components of EBHC at different levels of ME (UG, PG, mixed). Most SRs assessed a range of EBHC related outcomes using a variety of assessment tools. Two SRs included randomised controlled trials (RCTs) only, while 20 reviews included RCTs and various types of non-RCTs. Diversity of study designs and teaching activities as well as aggregated findings at the SR level preven

The Xinjiang Uyghur Autonomous Region (xuar) is the site of the largest mass repression of an ethnic and/or religious minority in the world today characterised by extra-judicial detention of Uyghurs in ‘re-education’ centres, pervasive surveillance, and repression of Uyghur ethnic identity. While Beijing frames such draconian measures as necessary ‘counter-terrorism’ measures, the intersection between concern for the ‘welfare’ of subject populations and the desire to eradicate ‘defective’ elements of cultural identity central to the ‘re-education’ system in Xinjiang betray the fundamentally colonial nature of the Chinese Communist Party’s (ccp) endeavours in the region.

The Xinjiang Uyghur Autonomous Region (xuar) is the site of the largest mass repression of an ethnic and/or religious minority in the world today characterised by extra-judicial detention of Uyghurs in ‘re-education’ centres, pervasive surveillance, and repression of Uyghur ethnic identity. While Beijing frames such draconian measures as necessary ‘counter-terrorism’ measures, the intersection between concern for the ‘welfare’ of subject populations and the desire to eradicate ‘defective’ elements of cultural identity central to the ‘re-education’ system in Xinjiang betray the fundamentally colonial nature of the Chinese Communist Party’s (ccp) endeavours in the region.

Abstract Previous explanations on China's counterterrorism strategy have highlighted the results of China's strategy of repression in Xinjiang, the historical antecedents and institutional foundations of its counterterrorism policies, as well as international and domestic sources of China's counterterrorism strategy. While acknowledging the importance of all these dimensions, this article draws attention to a largely neglected feature of China's counterterrorism strategy: the Chinese party-state's social engineering of Xinjiang. Building on Maoist-era practices such as the mass line and the ‘friend vs. enemy’ binary, the Communist party under Xi Jinping has integrated surveillance technologies as part of its strategy of preventive counterterrorism and ‘de-extremization’. This article argues that the Chinese party-state's embrace of modern technologies, a weak liberal tradition in China, Xi Jinping's rise to power in late 2012, and the appointment of Chen Quanguo as Xinjiang's party-secretary in 2016, provides the socio-political background for the intensification of securitization, surveillance and introduction of ‘re-education and training centres’ in Xinjiang. Surveillance technologies now complement collective, face-to-face methods of surveillance and Maoist-era techniques of mass mobilization, enabling the Chinese party-state to govern and manage the biopolitical spaces of Uyghurs with greater intensity, according to the state's precise norms. The legalization and institutionalization of ‘de-extremization’ has also led to the shift from mass ‘de-extremization’ propaganda to ‘drip-irrigation’ ideological and political re-education of individuals deemed at risk of extremism. The result is an increased capacity by the Chinese party-state to surveil and control the region, and to more effectively negate the possibility of individual resistance.

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA

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Objectives: Delirium in critically ill adults is highly prevalent and has multiple negative consequences. To-date, trials of interventions to prevent or treat delirium report heterogenous outcomes. To develop international consensus among key stakeholders for a core outcome set for future trials of interventions to prevent and/or treat delirium in critically ill adults. Design: Core outcome set development, as recommended by the Core Outcome Measures in Effectiveness Trials Handbook. Methods of generating items for the core outcome set included a systematic review and qualitative interviews with ICU survivors and family members. Consensus methods include a two-round web-based Delphi process and a face-to-face meeting using nominal group technique methods. Subjects: International representatives from three stakeholder groups: 1) clinical researchers, 2) ICU interprofessional clinicians, and 3) ICU survivors and family members. Setting: Telephone interviews, web-based surveys, and a face-to-face consensus meeting held at the 2019 European Delirium Intervention: None. Measurements and main results: Qualitative interviews with 24 ICU survivors and family members identified 36 potential outcomes; six were additional to the 97 identified from the systematic review. After item reduction, 32 outcomes were presented in Delphi Round 1; 179 experts participated, 38 ICU survivors/family members (21%), 100 clinicians (56%), 41 researchers (23%). Three additional outcomes were added to Round 2; 134 Round 1 participants (75%) completed it. Upon conclusion of the consensus building processes, the final core outcome set comprised seven outcomes: delirium occurrence (including prevalence or incidence); delirium severity; time to delirium resolution; health-related quality of life; emotional distress (i.e., anxiety, depression, acute and posttraumatic stress); cognition (including memory); and mortality. Conclusions: This core outcome set, endorsed by the American and Australian Delir

Background Antenatal steroids (ANS) are standard of care for women judged to be at imminent risk of preterm delivery. Worldwide, there is significant variation in ANS dosing strategy, selection for treatment criteria, and agent choice. This, combined with very limited optimization of ANS use per se means that treatment efficacy is highly variable and the rate of respiratory distress syndrome is decreased perhaps as little as 40%. In some cases, ANS use is associated with limited benefit and potential harm. Objective We hypothesized that individual differences in maternal and fetal steroid exposure would contribute to observed variability in ANS treatment efficacy. Using a chronically catheterized sheep model of pregnancy, we aimed to explore the relationship between materno-fetal steroid exposure and ANS treatment efficacy as determined by functional lung maturation in preterm lambs undergoing ventilation. Methods Ewes carrying a single fetus had surgery to catheterize a fetal and maternal jugular vein at 119 days’ gestation. Animals recovered for 24h before being randomized to either: i) a single maternal intramuscular injection (IM) of 2ml saline (Negative Control Group, n=10); or ii) a single maternal IM of 0.25mg/kg betamethasone phosphate + acetate (ANS Group, n=20). Serial maternal and fetal plasma samples were collected from each animal over 48h before fetuses were delivered and ventilated for 30 minutes. Total and free plasma betamethasone concentration was measured by mass spectrometry. Fetal lung tissue was collected for analysis using quantitative polymerase chain reaction. Results One animal of the Control Group and one animal from the ANS Group had did not complete their treatment protocol and were removed from analyses. Animals in the ANS Group were divided into a Responder (n=12/19) Sub-Group and a Non-Responder Sub-Group (n=7/19) using a cut-off of a PaCO2 at 30 minutes ventilation within 2SD of the mean value from saline-treated Negative Control Gro

Mesangial metrics reflect glomerular filtration surface area in diabetes. The point-sampled intercept (PSI) method is the conventional method to calculate these parameters. However, this is time consuming and subject to underestimation. We introduce a novel three-dimensional (3D) reconstruction method applicable to light microscopy to measure mesangial metrics. Transmission electron microscopy (TEM), PSI and our new 3D imaging methods were used to quantify mesangial metrics from 22 patients with type 2 diabetes, normo-, micro- and macroalbuminuria and an estimated glomerular filtration rate of <60mL/min/1.73m2. Repeated-measures ANOVA test was used to test the equality of the measurement means from the three methods and the degree of inter method variability. Repeated-measures and post-estimation ANOVA tests together with correlation coefficient measurements were used to compare the methods with TEM as reference. There was a statistically significant difference in mesangial volume measurements (F(2, 16)=15.53, p=0.0002). The PSI method underestimated measurements compared to TEM and 3D methods by 30% (p=0.001) and 15%, respectively (p<0.001). 3D and TEM measurements did not differ significantly. 3D reconstruction is a reliable and time efficient method for calculating mesangial metrics. It may prove to be a useful tool in clinical and experimental diabetic kidney disease.