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ImportanceUncombable hair syndrome (UHS) is a rare hair shaft anomaly that manifests during infancy and is characterized by dry, frizzy, and wiry hair that cannot be combed flat. Only about 100 known cases have been reported so far.ObjectiveTo elucidate the genetic spectrum of UHS.Design, Setting, and ParticipantsThis cohort study includes 107 unrelated index patients with a suspected diagnosis of UHS and family members who were recruited worldwide from January 2013 to December 2021. Participants of all ages, races, and ethnicities were recruited at referral centers or were enrolled on their own initiative following personal contact with the authors. Genetic analyses were conducted in Germany from January 2014 to December 2021.Main Outcomes and MeasuresClinical photographs, Sanger or whole-exome sequencing and array-based genotyping of DNA extracted from blood or saliva samples, and 3-dimensional protein modeling. Descriptive statistics, such as frequency counts, were used to describe the distribution of identified pathogenic variants and genotypes.ResultsThe genetic characteristics of patients with UHS were established in 80 of 107 (74.8%) index patients (82 [76.6%] female) who carried biallelic pathogenic variants in PADI3, TGM3, or TCHH (ie, genes that encode functionally related hair shaft proteins). Molecular genetic findings from 11 of these 80 individuals were previously published. In 76 (71.0%) individuals, the UHS phenotype were associated with pathogenic variants in PADI3. The 2 most commonly observed PADI3 variants account for 73 (48.0%) and 57 (37.5%) of the 152 variant PADI3 alleles in total, respectively. Two individuals carried pathogenic variants in TGM3, and 2 others carried pathogenic variants in TCHH. Haplotype analyses suggested a founder effect for the 4 most commonly observed pathogenic variants in the PADI3 gene.Conclusions and RelevanceThis cohort study extends and gives an overview of the genetic variant spectrum of UHS based on molecular genetic analyses of the largest worldwide collective of affected individuals, to our knowledge. Formerly, a diagnosis of UHS could only be made by physical examination of the patient and confirmed by microscopical examination of the hair shaft. The discovery of pathogenic variants in PADI3, TCHH, and TGM3 may open a new avenue for clinicians and affected individuals by introducing molecular diagnostics for UHS.

To report the prevalence of self-reported chronic pain and severity among young people in New Zealand and explore the relationships between pain and mental health, substance use, socialisation and school engagement.Prevalence of self-reported chronic pain frequency and severity are reported from an anonymous, representative cross-sectional self-administered health and well-being questionnaire by students aged 12-18 years in New Zealand. Multivariable models exploring chronic pain and mental health, substance use, socialisation and school engagement are reported controlling for age, sex, ethnicity, socio-economic status, disability and history of sexual abuse.Overall, 22.8% (95% confidence interval (CI) 21.2-24.5) of young people reported chronic pain for 6 months or more, with 3.2% (95% CI 3.1-4.5) reporting severe pain weekly or more often. Females and rural adolescents were more likely to report chronic and severe pain. Asian youth reported less pain than other ethnic groups. Increased severity of pain was associated more with poorer daily functioning and socialising than with frequency of pain. Severe pain occurring weekly or more often was more common among students who had a disability (2.3% 95% CI 1.8-2.7 vs. 9.8%, 95% CI 7.2-12.5) or a history of sexual abuse (2.4% 95% 1.9-2.9 vs. 8.5%, 95% CI 6.3-10.5). Those reporting chronic pain had higher proportions of self-reported significant depressive symptoms, lower well-being, lower school engagement and lower access to health care, particularly for those reporting higher levels of intensity and frequency of pain.Chronic pain is common in adolescent populations, and has a significant association with decreased daily functioning, socialising, school engagement and mental well-being. Adolescents with chronic pain report significant unmet health-care needs.

We report the case of a 65-year-old woman presenting with a 15-month history of recurrent episodes of focal alopecia at the site of a bluish plaque on the vertex of her scalp. Histopathological examination revealed an admixture of focally nested oval, dendritic or epithelioid melanocytes together with slender spindle cells and occasional melanocytes. The spindle cells were positive for S100 and focally positive for epidermal membrane antigen, while the melanocytes were positive for S100 and Melan A.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma. SS frequently spreads to other locations, referred to as metastatic SS (mSS) and is associated with a high death rate. Patients treated with first-line chemotherapy (1L setting), may need further lines of treatment (≥2L setting), which commonly involve the drugs pazopanib and trabectedin. This study assessed how well pazopanib and trabectedin work in people with ≥2L mSS, by examining both clinical trial (CT) and real-world (RW) studies. Overall, findings across 16 studies showed that mSS patients lived approximately 10 months after treatment with pazopanib or trabectedin in the ≥2L setting, and this was similar across both agents (10.3 months for pazopanib; 10.4 months for trabectedin) and between the CT (10.8 months) and the RW (9.9 months) settings. In terms of response to treatment, a higher percentage of people appeared to respond in RW settings (17.7%) than in CTs (9.5%), and to pazopanib (18.9%) compared with trabectedin (12.3%). These results show there is a need for better treatments for patients with previously treated mSS. These findings are useful benchmarks for the development of future treatment approaches for this rare disease.

Aims and background The resurrection plant Myrothamnus flabellifolia tolerates complete desiccation and is a great model for studying how plants cope with extreme drought. Root-associated microbes play a major role in stress tolerance and are an attractive target for enhancing drought tolerance in staple crops. However, how these dynamics play out under the most extreme water limitation remains underexplored. This study aimed to identify bacterial and fungal communities that tolerate extreme drought stress in the bulk soil, rhizosphere, and endosphere of M. flabellifolia. Methods High-throughput amplicon sequencing was used to characterise the microbial communities associated with M. flabellifolia. Results The bacterial phyla that were most abundant across all compartments were Acidobacteriota, Actinobacteriota, Chloroflexota, Planctomycetota, and Pseudomonadota, while the most abundant fungal phyla were Ascomycota and Basidiomycota. Although the bulk soil hosted multiple beneficial root-associated microbes, the rhizosphere compartment showed the highest functional diversity of bacteria and fungi. In contrast, the endosphere exhibited a low abundance and diversity of microbes. These findings share consistent with the theory that M. flabellifolia recruits soil microbes from the bulk to the rhizosphere and finally to the endosphere. It is possible that these microbes could promote drought tolerance in associated plant tissues. Conclusion We find that compartments act as the major driver of microbial diversity, but the soil physicochemical factors also influence microbial composition. These results suggest that the root-associated microbiome of M. flabellifolia is highly structured and may aid in plant function.

Introduction. Infection due to Capnocytophaga canimorsus may result in a wide variety of clinical presentations. We present a case of life-threatening Capnocytophaga canimorsus infection with evolution of ecchymosis to purpura fulminans. Case description. We present a case of a 43-year-old male with a significant history of alcohol use who presented with features of sepsis following a dog bite. This was associated with a striking, widespread purpuric rash. A causative pathogen, C. canimorsus was identified through blood culture and 16S RNA sequencing. His initially purpuric rash underwent bullous change and was diagnosed clinically as purpura fulminans, confirmed on skin biopsy. He made a full recovery with prompt antimicrobial therapy, initially with amoxiclav/clavulanic acid but escalated to clindamycin and meropenem due to clinical deterioration and concerns of beta-lactamase resistance. Discussion . b-lactamase producing Capnocytophaga strains are of increasing concern. This particular concern is reflected in our case as five days into treatment with b-lactamase inhibitor combination therapy the patients clinical condition deteriorated but demonstrably improved on switching to a carbapenem. The development of biopsy proven purpura fulminans in this immunocompetent case is a rare severe manifestation of the previously reported manifestation of DIC in Capnocytophaga septicaemia. The case reported describes characteristics common with other DIC presentations such as the presence of clinical risk factors (history of alcohol excess) and symmetrical involvement. However, an unusual feature in that initial purpuric lesions were followed by the development of a bullous appearance and peripheral necrotic features concerning for purpura fulminans and confirmed with skin biopsy.

Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent channel block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits – including transmembrane AMPAR regulatory proteins, cornichons, and GSG1L – which are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here, we show that the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution results in a complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, completely blocks outward synaptic currents. Thus, our results identify a functional measure of CP-AMPARs, that is unaffected by their auxiliary subunit content.

BACKGROUND Adolescents and young adults have health needs which are distinctly different from children and adults. A lack of education and training is reported by clinicians to be one of the main barriers to providing comprehensive developmentally appropriate care to young people, including the provision of confidential healthcare and taking a holistic approach. AIM This study documents the current provision of care to young people on an adult inpatient medical ward at a large tertiary teaching hospital in Auckland. METHODS Forty-three staff and 40 patients aged 16-24 years on an adult medical ward completed surveys, which were based on the Northern Regional Alliance, Northern Regional Youth Health Network Standards for Quality Care for Adolescents and Young Adults in Secondary or Tertiary Care. RESULTS Few staff (12%) had completed any specific training in looking after adolescent and young adult (AYA) patients. Confidentiality was not routinely discussed with young people by 50% of clinicians, and only 23% of staff reported that they see a young person alone as part of their consultation or admission. Less than half of young people reported receiving a comprehensive psychosocial assessment that included sexual health, mental health and suicide, and safety. CONCLUSIONS Key components of comprehensive developmentally appropriate healthcare were not regularly carried out by staff on an adult medical ward. These findings suggest that further education and training, and service improvements are needed in tertiary adult hospital settings. This article is protected by copyright. All rights reserved.

Heide A Stirnadel-Farrant,1 George Mu,2 Selin Cooper-Blenkinsopp,1 Rosemary O Schroyer,3 Kevin S Thorneloe,4 Ewen M Harrison,5 Susan MS Andrews6 1Department of WorldWide Epidemiology, GlaxoSmithKline, London, UK; 2Department of Data, Methods, and Analytics, GlaxoSmithKline, Collegeville, PA, USA; 3Department of Biostatistics, GlaxoSmithKline, Collegeville, PA, USA; 4Department of Translational Medicine, GlaxoSmithKline, Collegeville, PA, USA; 5Department of Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK; 6Department of Global Clinical Operations Development R&D, GlaxoSmithKline, Research Triangle Park, NC, USACorrespondence: Susan MS Andrews, Global Clinical Operations Development R&D GlaxoSmithKline Five Moore Drive, Research Triangle Park, NC, 27709-3398, USA, Tel +1-(919) 649-3944, Email susan.m.andrews@gsk.comPurpose: A variety of definitions for delayed graft function (DGF) have been proposed, but none has consistently been shown to be superior for predicting long-term graft outcomes for kidney donation after circulatory death (DCD) transplantation. In this study, real-world clinical outcome data following DCD transplantation were explored to determine the value of various DGF definitions for predicting graft survival.Patients and Methods: Data from 4 centers registered in the UK-based National Health Service Blood and Transplant registry (2010 to mid-2015) were used to assess 4 definitions of DGF in this retrospective chart review study.Results: Depending on the definition used, the frequency of DGF ranged from 119/362 (32.9%) when DGF was determined with available registry data and based on a requirement for dialysis within 7 days post-transplantation, to 224/315 (71.1%) when based on failure to achieve a 10% fall in serum creatinine (SCr) versus baseline per 24 hours averaged over the first 72 hours. Patients without clinical DGF as determined by a physician upon chart review, or when defined as < 30% reduction in baseline SCr within 7 days post-transplantation with or without dialysis, had significantly better graft survival probability 1 year (hazard ratio 2.08 and 4.48, respectively) and 5 years post-transplant, whereas serum creatinine level over the first 72 hours post-transplant was not predictive of graft survival at 1 year. Patients with clinical DGF upon physician chart review also had higher SCr, lower estimated glomerular filtration rate levels, and were dialyzed more (2.3 days) versus patients without (0.2 days).Conclusion: Delayed graft function, determined clinically or using a functional definition, is associated with poorer renal function and remains a useful predictor of graft survival at 1 year after DCD kidney transplantation.Keywords: delayed graft function, DGF, donation after circulatory death, DCD, serum creatinine, SCr

Background: Indigenous children in colonised nations experience high rates of health disparities linked to historical trauma resulting from displacement and dispossession, as well as ongoing systemic racism. Skin infections and their complications are one such health inequity, with the highest global burden described in remote-living Australian Aboriginal and/or Torres Strait Islander (hereafter respectfully referred to as Aboriginal) children. Yet despite increasing urbanisation, little is known about the skin infection burden for urban-living Aboriginal children. More knowledge is needed to inform service provision, treatment guidelines and community-wide healthy skin strategies. In this pilot study we aimed to test the feasibility and design of larger multi-site observational studies, provide initial descriptions of skin disease frequency and generate preliminary hypotheses of association. Methods: This project has been co-designed with local (Noongar) Elders to provide an Australian-first description of skin health and disease in urban-living Aboriginal children. In collaboration with an urban Aboriginal Community Controlled Health Organisation (Derbarl Yerrigan Health Service), we conducted a week-long cross-sectional observational cohort study of Aboriginal children (0–18 years) recruited from the waiting room. Participants completed a questionnaire, skin examination, clinical photos, swabs and received appropriate treatment. We assessed the feasibility and impact of the pilot study. Results: From 4–8 October 2021, we recruited 84 Aboriginal children of whom 80 (95%) were urban-living. With a trusted Aboriginal Health Practitioner leading recruitment, most parents (or caregivers) who were approached consented to participate. Among urban-living children, over half (45/80, 56%) of parents described a current concern with their child’s skin, hair and/or nails; and one third (26/80, 33%) reported current itchy skin. Using a research-service model, 27% (21/79) of examined urban-living participants received opportunistic same-day treatment and 18% (14/79) were referred for later review. Conclusions: This co-designed pilot study to understand skin health in urban-living Aboriginal children was feasible and acceptable, with high study participation and subsequent engagement in clinical care observed. Co-design and strong involvement of Aboriginal people to lead and deliver the project was crucial. The successful pilot has informed larger, multi-site observational studies to more accurately answer questions of disease burden and inform development of healthy skin messages for urban-living Aboriginal children.

Vegetative desiccation tolerance (VDT), the ability of such tissues to survive the near complete loss of cellular water, is a rare but polyphyletic phenotype. It is a complex multifactorial trait, typified by some near universal (core) factors but with many and varied adaptations due to plant architecture, biochemistry and biotic/abiotic dynamics of particular ecological niches. The ability to enter into a quiescent biophysically stable state is what ultimately determines desiccation tolerance. Thus, understanding of the metabolomic complement of plants with VDT gives insight into the nature of survival as well as evolutionary aspects of VDT. In this study we measured the soluble carbohydrate profiles and the polar, TMS-derivatisable metabolomes of 7 phylogenetically diverse species with VDT, in contrast with 3 desiccation sensitive (DS) species, under conditions of full hydration, severe water deficit stress, and desiccated.Our study confirmed the existence of core mechanisms of VDT systems relying on either constitutively abundant trehalose, or the accumulation of raffinose family oligosaccharides and sucrose, with threshold ratios conditioned by other features of the metabolome. DS systems did not meet these ratios. Considerable chemical variations among VDT species suggest that similar stresses, e.g. photosynthetic stress, are dealt with using different chemical regimes. Furthermore, differences in timing of metabolic shifts suggest there is not a single “desiccation programme”, but that subprocesses are coordinated differently at different phases of drying. There is likely to be constraints on the composition of a viable dry state and how different adaptive strategies interact with the biophysical constraints of VDT.

Aims and Background The resurrection plant Myrothamnus flabellifolia tolerates complete desiccation and is a great model for studying how plants cope with extreme drought. The response to desiccation in M. flabellifolia leaves has been studied extensively, but little is known about how the associated microbiome contributes to desiccation tolerance. Root-associated microbes play a major role in stress tolerance, and are an attractive target for enhancing drought tolerance in staple crops. However, how these dynamics play out under the most extreme water limitation remains underexplored. Methods The high-throughput amplicon metagenomic technique was used to investigated the bacterial and fungal communities in the bulk soil, rhizosphere, and endosphere of the M. flabellifolia. Results The bacterial phyla that were most abundant across all compartments were Acidobacteriota, Actinobacteria, Chloroflexi, Planctomycetes andProteobacteria, while fungal phyla were Ascomycotaand Basidiomycota. Although the bulk soil hosted multiple beneficial root-associated microbes, the rhizosphere compartment showed the highest functional diversity of bacteria and fungi. In contrast, the endosphere exhibited a low abundance and diversity of microbes. These findings suggest that M. flabellifolia recruits soil microbes from bulk to rhizosphere, many of which may confer extreme drought tolerance and promote plant growth. Conclusion The diverse rhizosphere microbiome is filtered to result in a highly selective endosphere microbiome. We find that compartment niches act as the major driver of microbial diversity, but that soil physicochemical factors also influence the microbial composition. These results suggest that the root-associated microbiome of M. flabellifolia is highly structured and may aid in plant function.

A scoping review to identify core components in effective symptom self-management interventions among adults with chronic illness.

AMPA-type gultamate receptors (AMPARs) mediate excitatory signaling in the brain and are therapeutic targets for the treatment of diverse neurological disorders. The receptors interact with a variety of auxiliary subunits, including the transmembrane AMPAR regulatory proteins (TARPs). The TARPs influence AMPAR biosynthesis and trafficking and enhance receptor responses by slowing desensitization and deactivation and increasing single-channel conductance. TARP

BACKGROUND Lack of validated and responsive outcome measures in the management of Frontal Fibrosing Alopecia (FFA) significantly limits our ability to assess disease progression and treatment response over time. OBJECTIVES The aim of this study was to understand how FFA extent and progression is currently assessed in UK specialist centres, validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and identify pragmatic advice to improve FFA management in clinic. METHODS Consultant Dermatologists with a specialist interest in hair loss (n=17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images, with assessment repeated 3 months later (to assess intra-individual variability) and 12 months later (to test whether inter-individual accuracy could be improved with simple instruction). RESULTS All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques between our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement (ICC 0.613; 95% CI: 0.398 to 0.848), yet intra-rater reliability was found to be poor with wide limits of agreement (-8.71mm to 9.92mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (questionnaire 3), inter-rater reliability improved significantly, with an ICC 0.702 suggesting moderate agreement (95% CI: 0.508 to 0.890; p

Objective To determine men's satisfaction with and the potential acceptability of 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) when used for 28 days as an experimental, once-daily, oral hormonal male contraceptive (HMC). Study design We surveyed participants from a double-blind, randomized, placebo-controlled, phase 1 clinical trial, examining their experience with and willingness to use daily oral 11β-MNTDC for male contraception. Results Of 42 trial participants, 40 (30 11β-MNTDC, 10 placebo) completed baseline and end-of-treatment surveys. Based on a 28-day experience, few cited any baseline concerns about safety and drug adherence. Following treatment, nearly three-quarters (72.5%) of participants reported satisfaction with the study drug and nearly all (92.5%) would recommend the method to others. More than half of participants would be willing to pay for the study drug (62.5%) and indicated that the method exceeded initial expectations (53.9%). Nearly 90% reported that taking the pill was easy to remember and did not interfere with their daily routines. Approximately one-third of participants reported bothersome side effects (37% 11β-MNTDC vs. 20% placebo, p = 0.45). Given the option, 42% of participants would prefer a daily HMC pill over injectable regimens or a daily topical gel. Conclusion A majority of participants in this short-term trial of daily oral 11β-MNTDC reported satisfaction with the regimen, would recommend it to others, and would pay to use the drug as HMC despite some bothersome side effects. Implications Oral 11β-MNTDC would be an acceptable and preferable method among men desiring reversible hormonal male contraception (HMC). These data support further trials of novel oral HMCs such as 11β-MNTDC.

Cet article se donne pour but de tracer mais egalement d’interroger l’influence et la presence de Scott chez Balzac. Malgre la justesse, a bien des egards, du celebre poncif de D’Arthez analyste de Scott dans Illusions perdues, et du role incontestable de l’Ecossais comme inspiration de Balzac des ses debuts, nous proposons une autre lecture plus large et a certains egards plus problematique : remettant en cause le reproche notoire de l’« Avant-propos » concernant la peinture scottienne de la femme, nous demontrons que les femmes les plus celebres des romans de Scott sont inspiratrices mais systematiquement occultees dans les romans de Balzac, tout comme le role inspirateur d’œuvres telles Kenilworth ou Les Eaux de Saint-Ronan et en fin de compte la paternite litteraire de l’auteur de Waverley lui-meme. Si Balzac trouve a redire, des 1824, a la gestion des masses chez Scott dans Redgauntlet, il finira en reinterpretant cette meme conception dans la scenographie de La Comedie humaine, a laquelle ce roman des plus intrigants du châtelain d’Abbotsford sert de point d’orgue.

Marine

To assess participation with a structured transition programme for adolescents with diabetes.Data from a regional cohort aged less than 16 years of age with type 1 (T1) and type 2 diabetes (T2D) in Auckland, New Zealand (2006-2016). Participation was defined as opting into a structured transition programme.Five hundrend and twelve adolescents who were to be transferred to adult care (476 type 1 (T1D) and 36 type 2 (T2D)), overall participation rate of 83%, 86% (408/476) with T1D compared to 47% (17/36) with T2D. Within the cohort of T1D, participation rates for Māori and Pacific were lower (74% and 77%, respectively) than New Zealand Europeans (88%, p = 0.020 and p = 0.039, respectively). Lower socio-economic status was associated with reduced participation (77%) compared to higher socio-economic status (90%, p = 0.002). Of the 476 T1D who participated, 408 (96%) subsequently attended at least one adult service clinic ("capture"). 42% attended an adult clinic within the planned 3 months, 87% at 6 months and retention in adult clinics over 5 years of follow-up was 78%. By contrast, the 68 young people with T1D who did not participate in the structured transition had a capture rate of 78% (p 0.001) and retention of 63% (p = 0.036).In adolescents with diabetes, a formal transition from a paediatric service was associated with high rates of adult capture and subsequent retention in adult care over a 5-year follow-up period. Low socio-economic status, Māori or Pacific ethnicity and T2D were associated with reduced participation in the structured transition programme.

The field of plant science has grown dramatically in the past two decades, but global disparities and systemic inequalities persist. Here, we analyzed ~300,000 papers published over the past two decades to quantify disparities across nations, genders, and taxonomy in the plant science literature. Our analyses reveal striking geographical biases—affluent nations dominate the publishing landscape and vast areas of the globe having virtually no footprint in the literature. Authors in Northern America are cited nearly twice as many times as authors based in Sub-Saharan Africa and Latin America, despite publishing in journals with similar impact factors. Gender imbalances are similarly stark and show remarkably little improvement over time. Some of the most affluent nations have extremely male biased publication records, despite supposed improvements in gender equality. In addition, we find that most studies focus on economically important crop and model species and a wealth of biodiversity is under-represented in the literature. Taken together, our analyses reveal a problematic system of publication, with persistent imbalances that poorly captures the global wealth of scientific knowledge and biological diversity. We conclude by highlighting disparities that can be addressed immediately and offer suggestions for long-term solutions to improve equity in the plant sciences.SIGNIFICANCE STATEMENTWe analyzed ~300,000 papers published over the past two decades to quantify global, gender, and taxonomic disparities in plant science. Our analyses reveal striking geographical biases that are correlated with national affluence. Gender imbalances were also evident, with far more papers led by authors with masculine names than authors with feminine names. Lastly, we identified substantial taxonomic sampling gaps. The vast majority of surveyed studies focused on major crop and model species and the remaining biodiversity accounted for only a fraction of publications. Taken together, our analyses represent an important addition to the growing conversation about diversifying and decolonizing science.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) are ligand-gated cationic channels formed from combinations of GluA1-4 subunits. Pathogenic variants of GRIA1-4 have been described in patients with developmental delay, intellectual disability, autism spectrum disorder, and seizures, with GRIA2 variants typically causing AMPAR loss of function. Here, we identify a novel, heterozygous de novo pathogenic missense mutation in GRIA2 (c.1928 CT, p.A643V, NM_001083619.1) in a 1-year-old boy with epilepsy, developmental delay, and failure to thrive. We made patch-clamp recordings to compare the functional and pharmacological properties of variant and wild-type receptors expressed in HEK293 cells, with and without the transmembrane AMPAR regulatory protein γ2. This showed GluA2 A643V-containing AMPARs to exhibit a novel gain of function, with greatly slowed deactivation, markedly reduced desensitization, and increased glutamate sensitivity. Perampanel, an antiseizure AMPAR negative allosteric modulator, was able to fully block GluA2 A643V/γ2 currents, suggesting potential therapeutic efficacy. The subsequent introduction of perampanel to the patient's treatment regimen was associated with a marked reduction in seizure burden, a resolution of failure to thrive, and clear developmental gains. Our study reveals that GRIA2 disorder can be caused by a gain-of-function variant, and both predicts and suggests the therapeutic efficacy of perampanel. Perampanel may prove beneficial for patients with other gain-of-function GRIA variants.

Purpose There is scant literature about the management of stillbirth and the subsequent risk of severe maternal morbidity (SMM). We aimed to assess the risk of SMM associated with stillbirths compared with live births and whether this differed by the presence of maternal comorbidities. Methods In this retrospective cohort study, we used a population-based dataset of all stillbirths and live births ≥ 20 weeks’ gestation in Western Australia between 2000 and 2015. SMM was identified using a published Australian composite for use with routinely collected hospital morbidity data. Maternal comorbidities were identified in the Hospital Morbidity Data Collection or the Midwives Notification System using a modified Australian chronic disease composite. Multivariable Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with SMM in analyses stratified by the presence of maternal comorbidities. Singleton and multiple pregnancies were examined separately. Results This study included 458,639 singleton births (2319 stillbirths and 456,320 live births). The adjusted RRs for SMM among stillbirths were 2.30 (95% CI 1.77, 3.00) for those without comorbidities and 4.80 (95% CI 4.11, 5.59) (Interaction P value Conclusion In Western Australia between 2000 and 2015, mothers of stillbirths both with and without any maternal comorbidities had an increased risk of SMM compared with live births. Further investigation into why women who have had a stillbirth without any existing conditions or pregnancy complications develop SMM is warranted.

The scientific objective of the first Edition (2017) of EMOSE is to review methods in marine plankton metagenomic analysis, essentially comparing the different filtration, sequencing and analysis pipelines used by recent initiatives, i.e. Tara Oceans, Malaspina and the Ocean Sampling Day. Already published data from these projects will be complemented by a new set of data obtained from a comparative experiment of protocols used in the three initiatives. The bulk of the analyses will be done during a 5‐day hands‐on session in Porto, and a virtual research environment will be used to plan the analysis and to work‐up a review paper.

Background. Patients with chronic obstructive pulmonary disease (COPD) typically experience multidimensional symptoms throughout the course of their disease, with burdensome physical symptoms, social isolation, and additional psychological suffering. COVID-19 lockdown resulted in restrictions on chronic care delivery at primary healthcare (PHC) facilities, and it is not known what the care experiences of patients with COPD were during this time.Objectives. To describe patient experiences of the impact of the lockdown on their needs and their experiences of the primary care received for their COPD.Methods. The data reported in this paper are from a cohort of 49 patients with COPD receiving primary care, recruited in February and March 2020, before recruitment was paused for COVID-19 lockdown, for a feasibility stepped-wedge hybrid type II design randomised controlled trial of integrated person-centred palliative care in primary care for patients with COPD in Cape Town, South Africa. Data are open-text responses from participants who responded to a single question on a validated measure of primary care consultation empathy (CARE), and describe patient experiences of the impact of the lockdown on the primary care received for their COPD, prior to crossover to trial intervention.Results. Thirty-two patients with COPD gave between 1 and 9 responses each to the open-ended question between March and December 2020. The average age of the participants was 58.6 years, and 53.1% (n=17) were female. Inductive analysis of the open-text data identified four main themes. Participants described decreased access to chronic care and a desire for more person-centred care in interactions with healthcare professionals. The socioeconomic ramifications of the COVID-19 lockdown added to the burden they experienced.Conclusion. The COVID-19 lockdown PHC service restrictions caused a disruption to the continuity of care for patients with COPD, with associated worry, anxiety and disappointment. Medication access was largely supported by the home delivery of chronic medication. We suggest that there are opportunities for providing more sustained support for patients with COPD through referrals to community health workers, and also through telephonic patient follow-up by primary care teams