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Campylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world's highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006-2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%-59.4%) than in human isolates (2.5%, 95% credible interval 0.3%-6.8%), underlining the importance of antimicrobial stewardship in livestock systems.

Background: Approximately 4.4 million people in England (8% of the total population) are living with a long-term neurological condition. Within this group of vulnerable individuals, there will be individuals living with severe spasticity that requires regular outpatient treatment with botulinum toxin injection. The closure of outpatient spasticity services during the pandemic impacted individuals who required spasticity treatment and their carers, as well as the specialist clinicians responsible for service delivery., Objectives: We aimed to gain insight into the experiences of individuals living with spasticity, their carers and a clinical spasticity service lead during the pandemic, and to reflect on potential learning for the future., Methods: A qualitative study was designed using semi-structured interviews conducted by telephone. Participants comprised patients living with a long-term neurological condition who attended outpatient spasticity clinics before the start of the pandemic in England, primary carers who accompanied patients attending these clinics and a clinical spasticity service lead. Data were audio recorded, transcribed, anonymised and coded. Data analysis utilised the One Sheet of Paper thematic approach to identify themes, which were discussed and analysed by the interdisciplinary research team and two patient and carer participants., Results: Out of the 11 participants recruited, aged 36-77 years, seven comprised people living with spasticity related to a long-term neurological condition, three were carers and one was a clinical spasticity service lead. Six participants were male and five were female. Among the participants, four were stroke survivors, two were living with spinal cord injury and one was living with multiple sclerosis. Analysis revealed six major themes: experience of living with spasticity during the pandemic; impact of the pandemic on patient, carer and clinician health; access to and experience of outpatient clinic appointments; coping strategies during the pandemic; system improvements; and learning from the pandemic period., Conclusion: These findings contribute research knowledge to a very limited research knowledge base and suggest that there is scope for improving system and service delivery through the allocation of research funding to senior clinicians working in this specialist area., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Dengue virus (DENV) is the most prevalent mosquito-borne Flavivirus that affects humans worldwide. Aedes albopictus, which is naturally infected with the bacteria Wolbachia, is considered to be a secondary vector of DENV. However, it was responsible for a recent DENV outbreak of unprecedented magnitude in Reunion Island, a French island in the South West Indian Ocean. Moreover, the distribution of the cases during this epidemic showed a spatially heterogeneous pattern across the island, leading to questions about the differential vector competence of mosquito populations from different geographic areas. The aim of this study was to gain a better understanding of the vector competence of the Ae. albopictus populations from Reunion Island for local DENV epidemic strains, while considering their infection by Wolbachia. Experimental infections were conducted using ten populations of Ae. albopictus sampled across Reunion Island and exposed to three DENV strains: one strain of DENV serotype 1 (DENV-1) and two strains of DENV serotype 2 (DENV-2). We analyzed three vector competence parameters including infection rate, dissemination efficiency and transmission efficiency, at different days post-exposition (dpe). We also assessed whether there was a correlation between the density of Wolbachia and viral load/vector competence parameters. Our results show that the Ae. albopictus populations tested were not able to transmit the two DENV-2 strains, while transmission efficiencies up to 40.79% were observed for the DENV-1 strain, probably due to difference in viral titres. Statistical analyses showed that the parameters mosquito population, generation, dpe and area of sampling significantly affect the transmission efficiencies of DENV-1. Although the density of Wolbachia varied according to mosquito population, no significant correlation was found between Wolbachia density and either viral load or vector competence parameters for DENV-1. Our results highlight the importance of using natural mosquito populations for a better understanding of transmission patterns of dengue., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hafsia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We recently showed that vestibular stimulation can produce a long-lasting alleviation of motor features in Parkinson's disease. Here we investigated whether components of the motor related cortical response that are commonly compromised in Parkinson's - the Bereitschaftspotential and mu-rhythm event-related desynchronization - are modulated by concurrent, low frequency galvanic vestibular stimulation (GVS) during repetitive limb movement amongst 17 individuals with idiopathic Parkinson's disease. Relative to sham, GVS was favourably associated with higher amplitudes during the late and movement phases of the Bereitschaftspotential and with a more pronounced decrease in spectral power within the mu-rhythm range during finger-tapping. These data increase understanding of how GVS interacts with the preparation and execution of voluntary movement and give added impetus to explore its therapeutic effects on Parkinsonian motor features., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Serine proteinase inhibitors (serpins) are a family of structurally similar proteins which regulate many diverse biological processes from blood coagulation to extracellular matrix (ECM) remodelling. Chondrogenesis involves the condensation and differentiation of mesenchymal stem cells (MSCs) into chondrocytes which occurs during early development. Here, and for the first time, we demonstrate that one serpin, SERPINA3 (gene name SERPINA3, protein also known as alpha-1 antichymotrypsin), plays a critical role in chondrogenic differentiation. We observed that SERPINA3 expression was markedly induced at early time points during in vitro chondrogenesis. We examined the expression of SERPINA3 in human cartilage development, identifying significant enrichment of SERPINA3 in developing cartilage compared to total limb, which correlated with well-described markers of cartilage differentiation. When SERPINA3 was silenced using siRNA, cartilage pellets were smaller and contained lower proteoglycan as determined by dimethyl methylene blue assay (DMMB) and safranin-O staining. Consistent with this, RNA sequencing revealed significant downregulation of genes associated with cartilage ECM formation perturbing chondrogenesis. Conversely, SERPINA3 silencing had a negligible effect on the gene expression profile during osteogenesis suggesting the role of SERPINA3 is specific to chondrocyte differentiation. The global effect on cartilage formation led us to investigate the effect of SERPINA3 silencing on the master transcriptional regulator of chondrogenesis, SOX9. Indeed, we observed that SOX9 protein levels were markedly reduced at early time points suggesting a role for SERPINA3 in regulating SOX9 expression and activity. In summary, our data support a non-redundant role for SERPINA3 in enabling chondrogenesis via regulation of SOX9 levels., Competing Interests: Declaration of compting interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study explored potential quality measures to improve skin cancer management in primary care settings, and the barriers and facilitators associated with their implementation., Design: Semistructured interviews and qualitative proforma surveys were conducted with skin cancer experts from a range of healthcare settings. Framework analysis was employed to identify key groups of quality measures within the domains of the Donabedian model of healthcare quality (structure, process, outcome). Interview and survey data were triangulated to identify common groups of quality measures, barriers and facilitators., Participants: We purposively recruited skin cancer experts from Australia and internationally with knowledge and experience in skin cancer management. The final sample consisted of 15 participants who had clinical or academic backgrounds., Results: Participants unequivocally expressed the need for quality measures to guide skin cancer care. Ten groups of quality measures were identified: three groups related to the structural elements of care (eg, diagnostic tools), four related to the processes of care (eg, diagnostic process) and three related to outcomes of care (eg, treatment outcomes). Implementation barriers included clinician resistance, system inadequacies and external factors (eg, patient risk). Facilitators included incentives, education, agreed and feasible indicators and support and guidance., Conclusions: To service a growing population of skin cancer patients in Australia, the role of primary care needs to be more clearly specified, and its care providers supported and more engaged in quality improvement processes. Structure, process and outcome quality measures, derived from detailed guidance for primary care settings, can be used to track practitioner performance and facilitate ongoing improvement., Competing Interests: Competing interests: DW is a member of the National Skin Cancer Centres board of directors., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The plasma protein binding (PPB) of a drug plays a key role in both its pharmacokinetic and pharmacodynamic properties. During lead optimisation, medium and high throughput methods for the early determination of PPB can provide important information about potential PKPD profile within a chemotype or between different chemotype series. Diffusion ordered spectroscopy (DOSY) is an NMR spectroscopic technique that measures the diffusion of a molecule through the magnetic field gradient, according to its molecular size/weight. Here, we describe the use of DOSY for a rapid and straightforward method to evaluate the PPB of drug molecules, using their binding to bovine serum albumin (BSA) as a model., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Doctors' strikes are legally permissible in the UK, with the situation differing in other countries. But are they morally permissible? Doug McConnell and Darren Mann have systematically attempted to dismiss the arguments for the moral impermissibility of doctors' strikes and creatively attempted to provide further moral justification for them. Unfortunately for striking doctors, they fail to achieve this. Meanwhile, junior doctors' strikes have continued in the UK through 2023 and have now extended into 2024. In this response, which focuses on the UK situation and specifically junior doctors' strikes in the National Health Service (NHS) in England, I will demonstrate a central problem with their arguments-namely that they underplay the harms caused by prolonged doctors' strikes by ignoring the harms to patients with cancer. This weakens their conclusion that strikes are morally permissible in terms of the conditions and thresholds they set. I then provide a psychological critique of their justification for strikes in terms of the interests of the public. It follows that invoking the controversial concept of supererogatory action is ungrounded but also absurd when you consider time-critical cancer care. If those representing striking doctors wish to maintain a modicum of moral respectability, they should mitigate for patients with cancer and negotiate reasonably and with urgency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dengue is a major public health concern in Reunion Island, marked by recurrent epidemics, including successive outbreaks of dengue virus serotypes 1 and 2 (DENV1 and DENV2) with over 70,000 cases confirmed since 2017., Methodology/principal Findings: In this study, we used Oxford Nanopore NGS technology for sequencing virologically-confirmed samples and clinical isolates collected between 2012 and 2022 to investigate the molecular epidemiology and evolution of DENV in Reunion Island. Here, we generated and analyzed a total of 499 DENV1, 360 DENV2, and 18 DENV3 sequences. By phylogenetic analysis, we show that different genotypes and variants of DENV have circulated in the past decade that likely originated from Seychelles, Mayotte and Southeast Asia and highly affected areas in Asia and Africa., Conclusions/significance: DENV sequences from Reunion Island exhibit a high genetic diversity which suggests regular introductions of new viral lineages from various Indian Ocean islands. The insights from our phylogenetic analysis may inform local health authorities about the endemicity of DENV variants circulating in Reunion Island and may improve dengue management and surveillance. This work emphasizes the importance of strong local coordination and collaboration to inform public health stakeholders in Reunion Island, neighboring areas, and mainland France., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Frumence et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cerebrovascular surgery has many intraoperative imaging modalities available. Modern technologies include intraoperative digital subtraction angiogram, indocyanine green (ICG) angiography, relative fluorescent measurement with ICG, and ultrasound. Each of these can be used effectively in the treatment of open aneurysm and arteriovenous malformation surgeries, in addition to arteriovenous fistula surgery, and cerebral bypass surgery., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the contribution of dizziness to postconcussion symptoms, depression, and anxiety symptoms., Setting: Mild traumatic brain injury (mTBI) service, Defence Medical Rehabilitation Centre, Stanford Hall., Participants: Two hundred eighty-three UK military personnel from the Royal Navy, Royal Airforce, Royal Marines, and British Army., Design: A retrospective analysis of data from the Ministry of Defence medical records database., Main Measures: Sixteen-item Rivermead Post Concussion Symptoms Questionnaire, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, The Dizziness Handicap Inventory., Results: Injuries from sports or falls were the most common mechanism of mTBI, accounting for 23%, respectively. Chi-square analysis indicated that individuals with dizziness and postconcussion symptoms (PCS) had greater severity of PCS, depression, and anxiety than those with PCS alone. Mediation analysis showed dizziness directly and independently influenced the severity of PCS, despite the indirect effects of mediating depression and anxiety symptoms., Conclusion: Comorbid dizziness and PCS were predictive of poorer mental health compared with PCS alone. In addition, dizziness directly influenced the severity of PCS irrespective of the indirect effects of mental health symptoms. These observations suggest that treating dizziness with vestibular rehabilitation may improve PCS and mental health., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation., Method: An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice., Results: Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise., Conclusion: Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.

Unilateral visual neglect is a condition that negatively impacts the lives of many stroke survivors. Studies have investigated different forms of vestibular stimulation as a potential therapy, but evidence is yet to be systematically reviewed. We therefore reviewed the effects of vestibular stimulation on outcomes of neglect and activities of daily living (ADL) for people with visual neglect. We searched relevant databases up until September 2022. Eligible articles included any form of vestibular stimulation, study design, or control condition. Included participants were 18 years or older, presenting with neglect following a haemorrhagic or ischaemic stroke. Relevant outcomes were clinically validated measures of neglect and ADL. Cochrane risk of bias tools were used to assess study quality. Meta-analyses and narrative methods were used to synthesize the data. Our search returned 17 relevant studies comprising 180 participants. Meta-analyses showed no difference between galvanic vestibular stimulation and sham conditions on outcomes, whereas caloric vestibular stimulation led to improvement compared to pre-stimulation scores. Narrative syntheses showed mixed results. Clinical and methodological heterogeneity was found both within and between studies. Overall, results were inconsistent regarding the effects of vestibular stimulation as a treatment for neglect. Further trials are warranted but require more careful methodological planning.

Many journals in ecology and evolutionary biology encourage or require authors to make their data and code available alongside articles. In this study we investigated how often this data and code could be used together, when both were available, to computationally reproduce results published in articles. We surveyed the data and code sharing practices of 177 meta-analyses published in ecology and evolutionary biology journals published between 2015-17: 60% of articles shared data only, 1% shared code only, and 15% shared both data and code. In each of the articles which had shared both (n = 26), we selected a target result and attempted to reproduce it. Using the shared data and code files, we successfully reproduced the targeted results in 27-73% of the 26 articles, depending on the stringency of the criteria applied for a successful reproduction. The results from this sample of meta-analyses in the 2015-17 literature can provide a benchmark for future meta-research studies gauging the computational reproducibility of published research in ecology and evolutionary biology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kambouris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Multiple studies suggest routine post-operative intensive care unit (ICU) stays after endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs) is unnecessary, though rates of ICU utilization nationwide are unknown. We aim to evaluate rates and characteristics of ICU utilization in patients undergoing elective endovascular repair of UIAs., Methods: This is a retrospective cohort study utilizing a nationwide private-payer database in the United States to evaluate the ICU utilization in patients undergoing elective endovascular repair of UIAs between 2005 and 2019. Demographics and pre-operative comorbidities as well as post-procedural complications and discharge status were compared. An analysis of charges and costs was also performed., Results: Among 6218 patients who underwent elective EVT of a UIA, 4890 (78.6%) were admitted to the ICU post-operatively. There were no differences in age, sex, or Charlson comorbidity scores in patients admitted to the ICU post-operatively compared to those admitted elsewhere. ICU utilization was more common in urban locations compared to rural. 12.7% of patients had ICU-specific needs sufficient to be billed by a critical care provider. Total provider costs were significantly higher in patients utilizing the ICU post-operatively, even among uncomplicated patients with routine discharges., Conclusion: Most patients undergoing elective endovascular UIA repair in the United States are admitted to the ICU postoperatively. Only 12.7% have ICU needs, and these patients are predictable from pre-operative characteristics or peri-operative complications. Reducing ICU use in this subgroup of patients may be an important target to improve healthcare value in this patient population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO., Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression., Results: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups., Conclusion: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life., Competing Interests: Declaration of competing interest Pinal Patel's Research Post was funded by Calea, Fresenius Kabi, UK., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Vestibular disorders are prevalent and debilitating conditions of the inner ear and brain which affect balance, coordination, and the integration of multisensory inputs. A growing body of research has linked vestibular disorders to cognitive problems, most notably attention, visuospatial perception, spatial memory, and executive function. However, the mechanistic bases of these cognitive sequelae remain poorly defined, and there is a gap between our theoretical understanding of vestibular cognitive dysfunction, and how best to identify and manage this within clinical practice. This article takes stock of these shortcomings and provides recommendations and priorities for healthcare professionals who assess and treat vestibular disorders, and for researchers developing cognitive models and rehabilitation interventions. We highlight the importance of multidisciplinary collaboration for developing and evaluating clinically relevant theoretical models of vestibular cognition, to advance research and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Smith, Wilkinson, Bodani and Surenthiran.)

Ducks and geese are little studied dispersal vectors for plants lacking a fleshy fruit, and our understanding of the traits associated with these plants is limited. We analyzed 507 faecal samples of mallard ( Anas platyrhynchos ) and Canada goose ( Branta canadensis ) from 18 natural and urban wetlands in England, where they are the dominant resident waterfowl. We recovered 930 plant diaspores from 39 taxa representing 18 families, including 28 terrestrial and five aquatic species and four aliens. Mallards had more seeds and seed species per sample than geese, more seeds from barochory and hydrochory syndromes, and seeds that on average were larger and from plants with greater moisture requirements (i.e., more aquatic). Mallards dispersed more plant species than geese in natural habitats. Plant communities and traits dispersed were different between urban (e.g., more achenes) and natural (e.g., more capsules) habitats. Waterfowl can readily spread alien species from urban into natural environments but also allow native terrestrial and aquatic plants to disperse in response to climate heating or other global change. Throughout the temperate regions of the Northern Hemisphere, the mallard is accompanied by a goose (either the Canada goose or the greylag goose) as the most abundant waterfowl in urbanized areas. This combination provides a previously overlooked seed dispersal service for plants with diverse traits., Competing Interests: Authors have no conflict of interest to declare., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The emergence of SARS-like coronaviruses is a multi-stage process from wildlife reservoirs to people. Here we characterize multiple drivers-landscape change, host distribution, and human exposure-associated with the risk of spillover of zoonotic SARS-like coronaviruses to help inform surveillance and mitigation activities. We consider direct and indirect transmission pathways by modeling four scenarios with livestock and mammalian wildlife as potential and known reservoirs before examining how access to healthcare varies within clusters and scenarios. We found 19 clusters with differing risk factor contributions within a single country (N = 9) or transboundary (N = 10). High-risk areas were mainly closer (11-20%) rather than far ( < 1%) from healthcare. Areas far from healthcare reveal healthcare access inequalities, especially Scenario 3, which includes wild mammals and not livestock as secondary hosts. China (N = 2) and Indonesia (N = 1) had clusters with the highest risk. Our findings can help stakeholders in land use planning, integrating healthcare implementation and One Health actions., (© 2023. The Author(s).)

Eutrophication and harmful algal blooms have severe effects on water quality and biodiversity in lakes and reservoirs. Ecological regime shifts of phytoplankton blooms are generally thought to be driven by the rapidly rising nutrient use efficiency of bloom-forming species over short periods, and often exhibit nonlinear dynamics. Regime shifts of trophic state, eutrophication, stratification, and clear or turbid waters are well-studied topics in aquatic ecology. However, information on the prevalence of regime shifts in relationships between trophic states and phytoplankton resource transfer efficiencies in ecosystems is still lacking. Here, we provided a first insight into regime shifts in nitrogen use efficiency of phytoplankton along the trophic state gradient. We explored the regime shifts of phytoplankton resource use efficiency and detected the tipping points by combining four temporal or spatial datasets from tropical to temperate zones in Asia and Europe. We first observed significant abrupt transitions (abruptness > 1) in phytoplankton nitrogen use efficiency along the trophic state gradient. The tipping point values were lower in subtropical/tropical waterbodies (mesotrophic states; TSIc: around 50) than those in temperate zones (eutrophic states; TSIc: 60-70). The regime shifts significantly reduced the primary production transfer efficiency via zooplankton (from 0.15 ± 0.03 to 0.03 ± 0.01; mean ± standard error) in the aquatic food web. Nitrogen-fixing filamentous cyanobacteria can drive eutrophication under mesotrophic state. Our findings imply that the time-window of opportunity for harmful algae prevention and control in lakes and reservoirs is earlier in subtropical/tropical regions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The appropriate choice of perioperative sedation during endovascular thrombectomy for ischemic stroke is unknown. Few studies have evaluated the role of nursing-administered conscious sedation supervised by a trained interventionalist., Objective: To compare the safety and efficacy of endovascular thrombectomy for ischemic stroke performed with nursing-administered conscious sedation supervised by a trained interventionalist with monitored anesthesia care supervised by an anesthesiologist., Methods: A retrospective review of a prospectively collected stroke registry was performed. The primary outcome was functional independence at 90 days, defined as a modified Rankin score of 0-2. Propensity score matching was performed to control for known confounders including patient comorbidities, access type, and direct-to-suite transfers., Results: A total of 355 patients underwent endovascular thrombectomy for large vessel occlusion between 2018 and 2022. Thirty five patients were excluded as they arrived at the endovascular suite intubated. Three hundred and twenty patients were included in our study, 155 who underwent endovascular thrombectomy with nursing-administered conscious sedation and 165 who underwent endovascular thrombectomy with monitored anesthesia care. After propensity score matching, there were 111 patients in each group. There was no difference in modified Rankin score 0-2 at 90 days (26.1% vs 35.1%, p =  0.190). Patients undergoing monitored anesthesia care received significantly more vasoactive medications (23.4% vs 49.5%, p <  0.001) and had a lower intraoperative minimum systolic blood pressure (134 vs 123   mmHg, p <  0.046). There was no difference in procedural efficacy, safety, intubation rates, and postoperative complications., Conclusion: Perioperative sedation with nursing-administered conscious sedation may be safe and effective in patients undergoing endovascular thrombectomy for ischemic stroke., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The use of laparoscopy for paediatric inguinal hernia repairs has increased significantly over the past 2 decades. However, there is significant variation in the reported recurrence rates in the literature, with many studies reporting higher rates than the open operation. This may be explained by the range of different techniques currently included under the term laparoscopic inguinal hernia repair. The purpose of this study is to determine whether dividing the hernia sac before ligation improves surgical outcomes following a paediatric laparoscopic inguinal hernia repair compared to ligation alone., Methods: A systematic review of the literature was performed following PRISMA guidelines of all studies reporting the outcomes following paediatric laparoscopic inguinal hernia repair where the technique was recorded as laparoscopic suture ligation alone (LS) or laparoscopic sac division and suture ligation (LSDS). Studies were assessed for risk of bias and exclusion criteria included reported follow-up of less than 6 months., Results: A total of 8518 LS repairs and 6272 LSDS repairs were included in the final analysis. LSDS repair was associated with a significantly lower recurrence rate (odds ratio 0.51, 95% CI 0.36-0.71, p = 0.001). There was no significant difference in the rates of testicular ascent or atrophy., Conclusion: Recreating the open operation by hernia sac division followed by suture ligation significantly reduces the risk of hernia recurrence., (© 2023. The Author(s).)

Developing tissues are sequentially patterned by extracellular signals that are turned on and off at specific times. In the zebrafish hindbrain, fibroblast growth factor (Fgf) signalling has different roles at different developmental stages: in the early hindbrain, transient Fgf3 and Fgf8 signalling from rhombomere 4 is required for correct segmentation, whereas later, neuronal Fgf20 expression confines neurogenesis to specific spatial domains within each rhombomere. How the switch between these two signalling regimes is coordinated is not known. We present evidence that the Zbtb16 transcription factor is required for this transition to happen in an orderly fashion. Zbtb16 expression is high in the early anterior hindbrain, then gradually upregulated posteriorly and confined to neural progenitors. In mutants lacking functional Zbtb16, fgf3 expression fails to be downregulated and persists until a late stage, resulting in excess and more widespread Fgf signalling during neurogenesis. Accordingly, the spatial pattern of neurogenesis is disrupted in Zbtb16 mutants. Our results reveal how the distinct stage-specific roles of Fgf signalling are coordinated in the zebrafish hindbrain., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

There has been a recent upsurge in human cases of leptospirosis in New Zealand, with wildlife a suspected emerging source, but up-to-date knowledge on this topic is lacking. We conducted a cross-sectional study in two farm environments to estimate Leptospira seroprevalence in wildlife and sympatric livestock, PCR/culture prevalence in wildlife, and compare seroprevalence and prevalence between species, sex, and age groups. Traps targeting house mice (Mus musculus), black rats (Rattus rattus), hedgehogs (Erinaceus europaeus) and brushtail possums (Trichosurus vulpecula) were set for 10 trap-nights in March-April 2017 on a dairy (A) and a beef and sheep (B) farm. Trapped wild animals and an age-stratified random sample of domestic animals, namely cattle, sheep and working dogs were blood sampled. Sera were tested by microagglutination test for five serogroups and titres compared using a Proportional Similarity Index (PSI). Wildlife kidneys were sampled for culture and qPCR targeting the lipL32 gene. True prevalence in mice was assessed using occupancy modelling by collating different laboratory results. Infection profiles varied by species, age group and farm. At the MAT cut-point of ≥ 48, up to 78% of wildlife species, and 16-99% of domestic animals were seropositive. Five of nine hedgehogs, 23/105 mice and 1/14 black rats reacted to L. borgpetersenii sv Ballum. The sera of 4/18 possums and 4/9 hedgehogs reacted to L. borgpetersenii sv Hardjobovis whilst 1/18 possums and 1/9 hedgehogs reacted to Tarassovi. In ruminants, seroprevalence for Hardjobovis and Pomona ranged 0-90% and 0-71% depending on the species and age group. Titres against Ballum, Tarassovi and Copenhageni were also observed in 4-20%, 0-25% and 0-21% of domestic species, respectively. The PSI indicated rodents and livestock had the most dissimilar serological responses. Three of nine hedgehogs, 31/105 mice and 2/14 rats were carrying leptospires (PCR and/or culture positive). True prevalence estimated by occupancy modelling in mice was 38% [95% Credible Interval 26, 51%] on Farm A and 22% [11, 40%] on Farm B. In the same environment, exposure to serovars found in wildlife species was commonly detected in livestock. Transmission pathways between and within species should be assessed to help in the development of efficient mitigation strategies against Leptospira., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moinet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Aotearoa New Zealand, 90% of patients with notified leptospirosis (a zoonotic bacterial disease) have been men working in agricultural industries. However, since 2008, the epidemiology of notified cases has been gradually changing, that is, more women are affected; there are more cases associated with occupations traditionally not considered high risk in New Zealand; infecting serovars have changed; and many patients experience symptoms long after infection. We hypothesized that there is a shift in leptospirosis transmission patterns with substantial burden on affected patients and their families., Objective: In this paper, we aimed to describe the protocols used to conduct a nationwide case-control study to update leptospirosis risk factors and follow-up studies to assess the burden and sources of leptospirosis in New Zealand., Methods: This study used a mixed methods approach, comprising a case-control study and 4 substudies that involved cases only. Cases were recruited nationwide, and controls were frequency matched by sex and rurality. All participants were administered a case-control questionnaire (study 1), with cases being interviewed again at least 6 months after the initial survey (study 2). A subset of cases from two high-risk populations, that is, farmers and abattoir workers, were further engaged in a semistructured interview (study 3). Some cases with regular animal exposure had their in-contact animals (livestock for blood and urine and wildlife for kidney) and environment (soil, mud, and water) sampled (study 4). Patients from selected health clinics suspected of leptospirosis also had blood and urine samples collected (study 5). In studies 4 and 5, blood samples were tested using the microscopic agglutination test to test for antibody titers against Leptospira serovars Hardjo type bovis, Ballum, Tarassovi, Pomona, and Copenhageni. Blood, urine, and environmental samples were also tested for pathogenic Leptospira DNA using polymerase chain reaction., Results: Participants were recruited between July 22, 2019, and January 31, 2022, and data collection for the study has concluded. In total, 95 cases (July 25, 2019, to April 13, 2022) and 300 controls (October 19, 2019, to January 26, 2022) were interviewed for the case-control study; 91 cases participated in the follow-up interviews (July 9, 2020, to October 25, 2022); 13 cases participated in the semistructured interviews (January 26, 2021, to January 19, 2022); and 4 cases had their in-contact animals and environments sampled (October 28, 2020, and July 29, 2021). Data analysis for study 3 has concluded and 2 manuscripts have been drafted for review. Results of the other studies are being analyzed and the specific results of each study will be published as individual manuscripts.., Conclusions: The methods used in this study may provide a basis for future epidemiological studies of infectious diseases., International Registered Report Identifier (irrid): DERR1-10.2196/47900., (©Shahista Nisa, Emilie Vallee, Jonathan Marshall, Julie Collins-Emerson, Polly Yeung, Gerard Prinsen, Jeroen Douwes, Michael G Baker, Jackie Wright, Tanya Quin, Maureen Holdaway, David A Wilkinson, Ahmed Fayaz, Stuart Littlejohn, Jackie Benschop. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.06.2023.)

This paper explores judgements about the replicability of social and behavioural sciences research and what drives those judgements. Using a mixed methods approach, it draws on qualitative and quantitative data elicited from groups using a structured approach called the IDEA protocol ('investigate', 'discuss', 'estimate' and 'aggregate'). Five groups of five people with relevant domain expertise evaluated 25 research claims that were subject to at least one replication study. Participants assessed the probability that each of the 25 research claims would replicate (i.e. that a replication study would find a statistically significant result in the same direction as the original study) and described the reasoning behind those judgements. We quantitatively analysed possible correlates of predictive accuracy, including self-rated expertise and updating of judgements after feedback and discussion. We qualitatively analysed the reasoning data to explore the cues, heuristics and patterns of reasoning used by participants. Participants achieved 84% classification accuracy in predicting replicability. Those who engaged in a greater breadth of reasoning provided more accurate replicability judgements. Some reasons were more commonly invoked by more accurate participants, such as 'effect size' and 'reputation' (e.g. of the field of research). There was also some evidence of a relationship between statistical literacy and accuracy., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Extensive drainage of peatlands in north-west Europe for the purposes of afforestation for timber production and harvesting has altered the carbon balance and biodiversity value. Large-scale restoration projects aim to reinstate hydrological conditions to keep carbon locked up in the peat and to restart active peat growth. Testate amoebae are an informal grouping of well-studied protists in peatland environments and as microbial consumers play an important role in nutrient and carbon cycling. Using a space for time substitution approach, this study investigated the response of testate amoebae assemblages and vegetation composition after tree removal on a drained raised bog. There was a clear difference in microbial assemblages between open and a chronosequenceof restoration areas. Results suggest microbial recovery after rewetting is a slow process with plant composition showing a faster response than the microbial assemblage. Mixotrophic testate amoebae had not recovered seventeen years following plantation removal and the establishment of Sphagnum mosses in the wetter microforms. These results suggest that vegetation composition and Testate amoeba assemblages respond differently to environmental drivers at forest-to-bog restoration areas. Local physicochemical peat properties were a stronger driver of the testate assemblage compared with vegetation. Complete recovery of microbial assemblages may take place over decadal timescales., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: An unprecedent increase in the number of cases and deaths reported from dengue virus (DENV) infection has occurred in the southwestern Indian ocean in recent years. From 2017 to mid-2021 more than 70,000 confirmed dengue cases were reported in Reunion Island, and 1967 cases were recorded in the Seychelles from 2015 to 2016. Both these outbreaks displayed similar trends, with the initial circulation of DENV-2 which was replaced by DENV-1. Here, we aim to determine the origin of the DENV-1 epidemic strains and to explore their genetic characteristics along the uninterrupted circulation, particularly in Reunion., Methods: Nucleic acids were extracted from blood samples collected from dengue positive patients; DENV-1 was identified by RT-qPCR. Positive samples were used to infect VERO cells. Genome sequences were obtained from either blood samples or infected-cell supernatants through a combination of both Illumina or MinION technologies., Results: Phylogenetic analyses of partial or whole genome sequences revealed that all DENV-1 sequences from Reunion formed a monophyletic cluster that belonged to genotype I and were closely related to one isolate from Sri Lanka (OL752439.1, 2020). Sequences from the Seychelles belonged to the same major phylogenetic branch of genotype V, but fell into two paraphyletic clusters, with greatest similarity for one cluster to 2016-2017 isolate from Bangladesh, Singapore and China, and for the other cluster to ancestral isolates from Singapore, dating back to 2012. Compared to publicly available DENV-1 genotype I sequences, fifteen non-synonymous mutations were identified in the Reunion strains, including one in the capsid and the others in nonstructural proteins (NS) (three in NS1, two in NS2B, one in NS3, one in NS4B, and seven in NS5)., Conclusion: In contrast to what was seen in previous outbreaks, recent DENV-1 outbreaks in Reunion and the Seychelles were caused by distinct genotypes, all likely originating from Asia where dengue is (hyper)endemic in many countries. Epidemic DENV-1 strains from Reunion harbored specific non-synonymous mutations whose biological significance needs to be further investigated., (© 2023. The Author(s).)

Overcoming the sluggish electrode kinetics of both oxygen reduction and evolution reactions (ORR/OER) with non-precious metal electrocatalysts will accelerate the development of rechargeable metal-air batteries and regenerative fuel cells. The authors investigated the electrochemical behavior and ORR/OER catalytic activity of core-porous shell Mn/Mn 3 O 4 nanoparticles in comparison with other manganese dioxides (β- and γ-MnO 2 ), and benchmarked against Pt/C and Pt/C-IrO 2 . Under reversible operation in O 2 -saturated 5 M KOH at 22 °C, the early stage activity of core-shell Mn/Mn 3 O 4 shows two times higher ORR and OER current density compared to the other MnO 2 structures at 0.32 and 1.62 V versus RHE, respectively. It is revealed that Mn(III) oxidation to Mn(IV) is the primary cause of Mn/Mn 3 O 4 activity loss during ORR/OER potential cycling. To address it, an electrochemical activation method using Co(II) is proposed. By incorporating Co(II) into MnO x , new active sites are introduced and the content of Mn(II) is increased, which can stabilize the Mn(III) sites through comproportionation with Mn(IV). The Co-incorporated Mn/Mn 3 O 4 has superior activity and durability. Furthermore, it also surpassed the activity of Pt/C-IrO 2 with similar durability. This study demonstrates that cost-effective ORR/OER catalysis is possible., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Skin cancer is a growing global problem and a significant health and economic burden. Despite the practical necessity for skin cancer to be managed in primary care settings, little is known about how quality of care is or should be measured in this setting. This scoping review aimed to capture the breadth and range of contemporary evidence related to the measurement of quality in skin cancer management in primary care settings. Six databases were searched for relevant texts reporting on quality measurement in primary care skin cancer management. Data from 46 texts published since 2011 were extracted, and quality measures were catalogued according to the three domains of the Donabedian model of healthcare quality (structure, process and outcome). Quality measures within each domain were inductively analysed into 13 key emergent groups. These represented what were deemed to be the most relevant components of skin cancer management as related to structure, process or outcomes measurement. Four groups related to the structural elements of care provision (e.g. diagnostic tools and equipment), five related to the process of care delivery (e.g. diagnostic processes) and four related to the outcomes of care (e.g. poor treatment outcomes). A broad range of quality measures have been documented, based predominantly on articles using retrospective cohort designs; systematic reviews and randomised controlled trials were limited., (© 2023 The Authors. Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Victor Goldman specialised in dental anaesthesia from an early age. He published his research all over the world and demonstrated how safety could be improved and how important monitoring of the anaesthetised patient should be. He made films, wrote books, created courses, and invented a myriad of apparatus to improve the speciality and to show trainees how dental anaesthesia should be performed. He was outspoken in his views and although well respected by his peers he did not receive many tangible accolades until the twilight of his career. His passing was hardly recorded, and his name is largely forgotten. He deserves wider recognition for his broad depth of contribution to his speciality.

Objective: Sialic acid-binding immunoglobulin-type lectins (Siglecs) are commonly present on immune cells and often mediate cell-to-cell interactions and signaling. Studies have shown the presence of Siglecs 1, 2, 5, 6, 10 and 14 on human spermatozoa. To the best of our knowledge, the expression of CD33 on spermatozoa has not yet been studied. Semen samples were collected from 25 healthy men with normal semen status. CD33 expression on purified spermatozoa was evaluated by flow cytometry methods., Results: The results demonstrate the expression of CD33 on the surface of purified spermatozoa. The mean (± SD) of MFI (mean fluorescence intensity) was 12.85 (± 1.33) and the mean percentage of spermatozoa that express CD33 was 73.75 (± 3.75). Results were obtained showing that spermatozoa express CD33 (or Siglec-3) on their surface. The physiological role of these molecules on spermatozoa remains to be determined. It is recommended that further research be undertaken regarding the role of Siglecs (such as CD33) on spermatozoa apoptosis., (© 2023. The Author(s).)

Background and Objective: There is a need for better integration of services across communities and sectors for people living with traumatic brain injury (TBI) to meet their complex needs. Building on insights gained from earlier pilot work, here we report the outcomes of a participatory workshop that sought to better understand the challenges, barriers and opportunities that currently exist within the care pathway for survivors of TBI., Methods: A diverse range of stakeholders from the acute and rehabilitation care pathway and the health and social care system were invited to participate in a 3-h workshop. The participants worked in four mixed subgroups using practice development methodology, which promotes person-centred, inclusive and participatory action., Results: Thematic analysis identified shared purposes and values that were used to produce a detailed implementation and impact framework for application at both the level of the care interface and the overarching integrated care system. A variety of enablers were identified that related to collective values and behaviours, case management, team leadership and integrated team working, workforce capability, evidence-based practice and resourcing. The clinical, economic, cultural and social outcomes associated with these enablers were also identified, and included patient safety, independence and well-being, reduced waiting times, re-admission rates, staff retention and professional development., Conclusion: The co-produced recommendations made within the implementation and impact framework described here provide a means by which the culture and delivery of health and social care services can be better tailored to meet the needs of people living with TBI. We believe that the recommendations will help shape the formation of new services as well as the development of existing ones., Patient or Public Contribution: Patient and public involvement have been established over a 10-year history of relationship building through a joint forum and events involving three charities representing people with TBI, carers, family members, clinicians, service users, researchers and commissioners, culminating in a politically supported event that identified concerns about the needs of people following TBI. These relationships formed the foundation for the interactive workshop, the focus of this publication., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The COVID-19 pandemic has caused unexpected disruptions to Western countries which affected women more adversely than men. Previous studies suggest that gender differences are attributable to: women being over-represented in the most affected sectors of the economy, women's labour market disadvantage as compared to their partners, and mothers taking a bigger share childcare responsibilities following school closures. Using the data from four British nationally representative cohort studies, we test these propositions. Our findings confirm that the adverse labour market effects were still experienced by women a year into the COVID-19 pandemic and that these effects were the most severe for women who lived with a partner and children, even if they worked in critical occupations. We show that adjusting for pre-pandemic job characteristics attenuates the gaps, suggesting that women were over-represented in jobs disproportionately affected by COVID-19 pandemic. However, the remaining gaps are not further attenuated by adjusting for the partner's job and children characteristics, suggesting that the adversities experienced by women were not driven by their relative labour market position, as compared to their partners or childcare responsibilities. The residual gender differences observed in the rates of active, paid work and furlough for those who live with partner and children point to the importance of unobserved factors such as social norms, preferences, or discrimination. These effects may be long-lasting and jeopardise women's longer-term position through the loss of experience, leading to reinforcement of gender inequalities or even reversal of the progress towards gender equality.

Introduction:  Opinion remains divided on whether to resect an asymptomatic congenital lung malformation (CLM) and on optimal timing of resection. This study aimed to determine if age at resection of CLM correlates with the presence of histological inflammation and/or incidence of prior antibiotic administration for lower respiratory tract infection (LRTI)., Materials and Methods:  A retrospective review of all CLMs resected between 2009 and 2021 was carried out. Data on antenatal detection, incidence of preoperative antibiotic use for LRTI, operative details, and histological reports were analyzed. Fisher's exact test and logistic regression were used to look for correlation between age at resection and (1) histological inflammation and/or (2) preoperative LRTI., Results:  A total of 102 patients underwent resection at age 14 months (interquartile range: 6-23). Eighty percent of children were asymptomatic in the neonatal period and 22% of these went on to develop a respiratory symptom. In total, 59% of specimens had histological evidence of inflammation, with a significantly higher rate of inflammation after 10 months of age (71 vs. 35%; p  = 0.0012). Logistic regression showed there was a positive correlation between age at resection and treatment for previous LRTI ( p  = 0.020)., Conclusion:  Detection rates of inflammation in specimens resected after 10 months of age are double the rates of those resected prior to 10 months. Delaying resection of CLMs showed a higher frequency of treatment of LRTI. Earlier resection may therefore be advantageous for centers pursuing a resection strategy for asymptomatic lesions., Competing Interests: None declared., (Thieme. All rights reserved.)

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fraser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception., Methods and Findings: Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring <10th percentile in ≥2/5 developmental domains (physical health and wellbeing, social competence, emotional maturity, language and cognitive skills, communication skills, and general knowledge). The second, educational outcome at age 7 to 9, was assessed using National Assessment Program-Literacy and Numeracy (NAPLAN) data (n = 342,311) and defined by overall z-score across 5 domains (grammar and punctuation, reading, writing, spelling, and numeracy). Inverse probability weighting with regression adjustment was used to estimate population average causal effects. The study included 412,713 children across the 2 outcome cohorts. Linked records were available for 4,697 IVF-conceived cases and 168,503 controls for AEDC, and 8,976 cases and 333,335 controls for NAPLAN. There was no causal effect of IVF-conception on the risk of developmental vulnerability at school-entry compared with spontaneously conceived children (AEDC metrics), with an adjusted risk difference of -0.3% (95% CI -3.7% to 3.1%) and an adjusted risk ratio of 0.97 (95% CI 0.77 to 1.25). At age 7 to 9 years, there was no causal effect of IVF-conception on the NAPLAN overall z-score, with an adjusted mean difference of 0.030 (95% CI -0.018 to 0.077) between IVF- and spontaneously conceived children. The models were adjusted for sex at birth, age at assessment, language background other than English, socioeconomic status, maternal age, parity, and education. Study limitations included the use of observational data, the potential for unmeasured confounding, the presence of missing data, and the necessary restriction of the cohort to children attending school., Conclusions: In this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BV has a paid role as a member of the Therapeutic Goods Administration. BV, FA and KS own shares in respective IVF companies (Monash IVF, Virtus Health and Melbourne IVF)., (Copyright: © 2023 Kennedy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The ever-increasing demand for flexible and portable electronics has stimulated research and development in building advanced electrochemical energy devices which are lightweight, ultrathin, small in size, bendable, foldable, knittable, wearable, and/or stretchable. In such flexible and portable devices, semi-solid/solid electrolytes besides anodes and cathodes are the necessary components determining the energy/power performances. By serving as the ion transport channels, such semi-solid/solid electrolytes may be beneficial to resolving the issues of leakage, electrode corrosion, and metal electrode dendrite growth. In this paper, the fundamentals of semi-solid/solid electrolytes (e.g., chemical composition, ionic conductivity, electrochemical window, mechanical strength, thermal stability, and other attractive features), the electrode-electrolyte interfacial properties, and their relationships with the performance of various energy devices (e.g., supercapacitors, secondary ion batteries, metal-sulfur batteries, and metal-air batteries) are comprehensively reviewed in terms of materials synthesis and/or characterization, functional mechanisms, and device assembling for performance validation. The most recent advancements in improving the performance of electrochemical energy devices are summarized with focuses on analyzing the existing technical challenges (e.g., solid electrolyte interphase formation, metal electrode dendrite growth, polysulfide shuttle issue, electrolyte instability in half-open battery structure) and the strategies for overcoming these challenges through modification of semi-solid/solid electrolyte materials. Several possible directions for future research and development are proposed for going beyond existing technological bottlenecks and achieving desirable flexible and portable electrochemical energy devices to fulfill their practical applications. It is expected that this review may provide the readers with a comprehensive cross-technology understanding of the semi-solid/solid electrolytes for facilitating their current and future researches on the flexible and portable electrochemical energy devices.

Objective: To evaluate the feasibility, usability, safety, and potential health benefits of using an exoskeleton device for rehabilitation of people living with multiple sclerosis., Design: Single-group preliminary study., Subjects: Eleven adults living with multiple sclerosis, with Expanded Disability Status Scores that ranged from 6 to 7.5 (mean age (standard deviation; SD) 54.2 (11.8) years), were recruited., Methods: Individual participants undertook a balance rehabilitation exercise programme using the Rex Rehab robotic exoskeleton device. Each participant undertook 4 × 45-60 min supervised, balance exercise sessions. Primary outcomes were: (i) the number of participants who completed the trial protocol safely, and (ii) the number and nature of adverse events reported. Secondary outcomes were: mobility; balance; spasticity; sleep; functional independence; quality of life; and device satisfaction., Results: Ten out of 11 participants completed the trial protocol safely. Four adverse events were recorded (1 serious), all of which were deemed unrelated to the trial. Secondary outcomes showed allied improvements in balance, joint mobility, spasticity and quality of life. All participants found the device acceptable to use., Conclusion: These results suggest that it is feasible and safe to use the Rex Rehab exoskeleton device to assist with balance rehabilitation for people living with multiple sclerosis.

The disturbance of microbiota composition in the female reproductive tract (FRT) can result in several reproductive disorders. Spermatozoa express toll like receptors (TLRs) and may encounter many types of microbiota in the FRT, however no study has been performed regarding the interaction between spermatozoa TLRs and FRT microbiota in unexplained recurrent spontaneous abortion (URSA) and fertile couples. In this study, we investigate the interaction of vaginal lactobacillus casei probiotic as a representative of FRT microbiota with TLR2 and 4 on spermatozoa. Ten fertile couples and ten URSA couples were involved in this study. Untreated and lactobacillus casei probiotic treated purified spermatozoa were evaluated for TLR2 and 4 expression by flow cytometry. Vaginal lactobacillus casei probiotic treatment of spermatozoa led to increased expression of TLR4 and decreased expression of TLR2 on spermatozoa in both URSA and fertile couples. Vaginal lactobacillus casei probiotic led to an increase in TLR4 expression and a decrease in TLR2 expression on spermatozoa in fertile and URSA groups. However, the disturbed expression of TLR2 and 4 was not completely correct, and further studies with other types of vaginal lactobacilli are needed. In contrast to our expectation, vaginal lactobacillus casei probiotic could not improve the disturbed expression of TLR2 and TLR4 in the RSA group. This could be due to small sample size and the use of one type of lactobacillus. Therefore, further study needs to be performed with other types of lactobacilli to determine the effect of microbiota and probiotics on spermatozoa function such as motility, acrosome reaction, sperm capacitation, sperm and egg fusion and spermatozoa motility and apoptosis and etc. Nevertheless, this study can provide a first step to investigate the effectiveness of vaginal microbiota on spermatozoa, and consequently design new strategies for RSA couples., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2022 The Authors.)

Richard Gordon (1921-2017) was a prolific writer of both humorous fiction and historical reviews. He trained in medicine at St Bartholomew's Hospital (Barts) in London and specialised in anaesthesia working at Hill End Hospital, St Albans (where a large proportion of Barts work took place to avoid the impact of the Blitz during the Second World War) and at the Radcliffe Infirmary, Oxford with Robert Macintosh. He published multiple papers and a book on trichlorethylene anaesthesia and edited a textbook of anaesthesia for medical students which ran for 10 editions. His gift for writing and his prominent public persona placed him in a unique position to highlight the importance of the newly emerging speciality of anaesthesia. He did the exact opposite of this and instead created a representation of an uninterested spectator to surgical activity, a representation which still persists in some quarters today.

Island communities are interesting study sites for microbial evolution during epidemics, as their insular nature reduces the complexity of the population's connectivity. This was particularly true on Reunion Island during the first half of 2021, when international travel was restricted in order to mitigate the risk for SARS-CoV-2 introductions. Concurrently, the SARS-CoV-2 Beta variant became dominant and started to circulate at high levels for several months before being completely replaced by the Delta variant as of October 2021. Here, we explore some of the particularities of SARS-CoV-2 genomic evolution within the insular context of Reunion Island. We show that island isolation allowed the amplification and expansion of unique genetic lineages that remained uncommon across the globe. Islands are therefore potential hotspots for the emergence of new genetic variants, meaning that they will play a key role in the continued evolution and propagation of COVID-19 as the pandemic persists., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Given their central role in supporting children's development, childcare professionals' overall physical and mental health is important. We evaluated the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among US childcare professionals., Methods: Data were obtained from US childcare professionals (N = 81,682) through an online survey from May 22, 2020, through June 8, 2020. We used multivariable logistic and linear regression models to assess the association of sociodemographic characteristics with 4 physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness., Results: For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) obesity. For mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and sex/gender disparities were found for physical health conditions but not mental health of childcare professionals during the COVID-19 pandemic., Conclusion: Our findings highlighted that childcare professionals' depression rates during the pandemic were higher than before the pandemic, and depression, stress, and asthma rates were higher than rates among US adults overall during the pandemic. Given the essential work childcare professionals provided during the pandemic, policy makers and public health officials should consider what can be done to support their physical and mental health.