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Abstract The purpose of this study was to examine how demographics, etiology, and clinical examination findings are related to visual outcomes in subjects with open globe injury (OGI) across a large and generalizable sample. A retrospective cohort analysis was performed using data collected from the electronic medical records of four tertiary university centers for subjects with OGI presenting from 2018 to 2021. Demographic information, injury mechanisms, clinical exam findings, visual acuity (VA) at presentation and most recent follow-up were recorded. In subjects with bilateral OGIs, only right eyes were included. A modified ocular trauma score (OTS) using presenting VA, the presence of perforating injury, OGI, and afferent pupillary defect was calculated. The risk of subjects’ demographic characteristics, ocular trauma etiology, clinical findings and modified OTS on the presence of monocular blindness at follow-up were assessed using univariable and multivariable regression models. 1426 eyes were identified. The mean age was 48.3 years (SD: ± 22.4 years) and the majority of subjects were men (N = 1069, 75.0%). Univariable analysis demonstrated that subjects of Black race were 66% (OR: 1.66 [1.25–2.20]; P

Abstract We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress β-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Abstract The IL-22RA1 receptor is highly expressed in the pancreas, and exogenous IL-22 has been shown to reduce endoplasmic reticulum and oxidative stress in human pancreatic islets and promote secretion of high-quality insulin from beta-cells. However, the endogenous role of IL-22RA1 signaling on these cells remains unclear. Here, we show that antibody neutralisation of IL-22RA1 in cultured human islets leads to impaired insulin quality and increased cellular stress. Through the generation of mice lacking IL-22ra1 specifically on pancreatic alpha- or beta-cells, we demonstrate that ablation of murine beta-cell IL-22ra1 leads to similar decreases in insulin secretion, quality and islet regeneration, whilst increasing islet cellular stress, inflammation and MHC II expression. These changes in insulin secretion led to impaired glucose tolerance, a finding more pronounced in female animals compared to males. Our findings attribute a regulatory role for endogenous pancreatic beta-cell IL-22ra1 in insulin secretion, islet regeneration, inflammation/cellular stress and appropriate systemic metabolic regulation.

Synchrotron light sources can provide the required spatial coherence, stability and control to support the development of advanced lithography at the extreme ultraviolet and soft X-ray wavelengths that are relevant to current and future fabricating technologies. Here an evaluation of the optical performance of the soft X-ray (SXR) beamline of the Australian Synchrotron (AS) and its suitability for developing interference lithography using radiation in the 91.8 eV (13.5 nm) to 300 eV (4.13 nm) range are presented. A comprehensive physical optics model of the APPLE-II undulator source and SXR beamline was constructed to simulate the properties of the illumination at the proposed location of a photomask, as a function of photon energy, collimation and monochromator parameters. The model is validated using a combination of experimental measurements of the photon intensity distribution of the undulator harmonics. It is shown that the undulator harmonics intensity ratio can be accurately measured using an imaging detector and controlled using beamline optics. Finally, the photomask geometric constraints and achievable performance for the limiting case of fully spatially coherent illumination are evaluated.

Background: Arbaeen in Iraq has been one of the largest mass gatherings during the COVID-19 pandemic with 14.5 million attendees in 2020. We set out to assess the prevalence of current or past COVID-19 among 2020 Arbaeen participants, and establish associations between COVID-19 test results, symptoms, and known recent exposure. Methods: This was a cross-sectional study involving participants who joined Arbaeen walk in Iraq in October 2020. COVID-19 PCR and/or rapid antibody test were conducted among consented participants. A short questionnaire was administered. Rapid antibody testing was done onsite. Nasal and throat swab samples were transferred to the laboratory for PCR testing. Results: A total of 835 (88.3% male; 11.7% female) participants were recruited. The most common symptom overall was cough (9.6%) followed by sore throat, fever, and loss of taste/smell (6.6%, 5.5%, and 5.0%, respectively). One in five (20.3%) participants reported close contact with a confirmed COVID-19 case in the past 14 days. Of the 237 participants with a PCR test, 18 (7.6%) were positive. Of the 765 participants with rapid antibody test, 19.3% tested positive for IgM, 39.3% for IgG, and 16.4% for both. Approximately 40% of the participants had evidence of current or past COVID-19 infection based on antibody and PCR. Conclusions: The almost 1 in 10 COVID-19 cases within such a multimillion person gathering, illustrates the difficulty in limiting the participation of infectious individuals in religious mass gatherings. There is a pressing need to explore measures to reduce the risk of transmission of infectious diseases at major mass gathering events.

Intraocular foreign bodies (IOFBs) remain a severe complication of ocular trauma commonly encountered worldwide. This literature review aimed to discuss current practice patterns, areas of controversy, and advances in the management of IOFBs. Injuries involving IOFBs carry significant ocular morbidity and management can be extremely challenging. A systematic approach to preoperative evaluation and IOFB surgical management is detailed in this article and should be applied in each case. The location and composition of an IOFB have important implications on surgical approach and timing, especially in cases of toxic metals and vegetable matter. The advantages, disadvantages, and previous literature regarding immediate versus delayed foreign body removal are presented. Surgical approaches are described, with an emphasis on posterior chamber IOFB management and removal via pars plana vitrectomy. Final visual acuity is variable, but approaches have been used to prognosticate outcomes including the Ocular Trauma Score. By synthesizing current IOFB literature, the goal is to provide practitioners with guidance that will maximize the chances of surgical success and patient outcomes.

En los estudios de la lingüística maya se suele identificar una clase excepcional de adverbios que se han llamado “adverbios dependientes”, “adverbios incorporados” o “adverbios clíticos”, entre otros nombres. Su característica más llamativa es que aparecen entre la raíz verbal y el pronombre del juego A o el marcador de aspecto o modo. El objetivo de este trabajo es presentar un argumento a favor de la idea de que, en el maya yucateco, tal clase de palabras debe tratarse como su propia categoría léxica, distinta de los adverbios, que denominamos preverbos. Presentamos evidencia morfológica, sintáctica y semántica a favor de distinguir los preverbos de los adverbios por un lado y de raíces incorporadas en bases verbales compuestas por otro. Finalmente, hacemos una clasificación semántica detallada de los preverbos y proponemos un análisis sintáctico que explica su comportamiento.

Summary: Retinoic acid (RA), controls the immunoregulatory functions of many immune cells, including dendritic cells (DCs), and is important for mucosal immunity. In DCs, RA regulates the expression of pattern recognition receptors and stimulates interferon production. Here, we investigated the role of RA in DCs in mounting immunity to respiratory syncytial virus (RSV). To abolish RA signaling in DCs, we used mice expressing a dominant negative form of retinoic acid receptor-α (RARα) under the CD11c promoter (CD11c-dnRARα). Paradoxically, upon RSV challenge, these animals had lower viral burden, reduced pathology, and greater Th1 polarized immunity than wild-type (WT) mice. Moreover, CD11c-dnRARα DCs infected with RSV showed enhancement in innate and adaptive immunity genes, while genes associated with viral replication were downregulated. These findings suggest that the absence of RA signaling in DCs enhances innate immunity against RSV infection leading to decreased viral load and reduced pathogenicity.

Abstract Rationale The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm). Methods and design PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10–14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Purpose This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings. Trial registration ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613 . Protocol: MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions—none.

Abstract Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. Previously, the current authors have discussed the similarities and differences between SANS and idiopathic intracranial hypertension to try to elucidate a possible pathophysiology. Recently, a theory has been advanced that SANS may occur secondary to failure of the glymphatic system caused by venous dilatation within the brain and optic nerves. There is recent evidence to suggest glymphatic obstruction occurs in childhood hydrocephalus, multiple sclerosis and syringomyelia due to venous outflow dilatation similar to that proposed in SANS. The purpose of the current paper is to discuss the similarities and differences between the known CSF and venous pathophysiology in SANS with these other terrestrial diseases, to see if they can shed any further light on the underlying cause of this microgravity-induced disease.

Abstract Senecavirus A (SVA) causes vesicular disease in swine and has been responsible for a rampant increase in the yearly number of foreign animal disease investigations conducted in the United States. Diagnostic investigations for SVA are typically performed by sampling animals individually, which is labor-intensive and stressful. Developing an alternative aggregate sampling method would facilitate the detection of this virus at the population level. In a preliminary study, SVA was detected in processing fluids (PF) collected in a breeding herd before and after outbreak detection. The objective of this study was to estimate the average number of weeks PF remain SVA-positive after an SVA outbreak. Ten farrow-to-wean breeding herds volunteered to participate in this studyby longitudinally collecting PF samples after an SVA outbreak was detected and submitting samples for RT-rtPCR testing. The PF samples from the 10 farms were SVA-positive for an average of 11.8 weeks after the outbreak. Here, we show that testing of PF may be a cost-effective method to detect SVA and help halt its spread in SVA-endemic regions.

Background and Aims: Hemostatic iron regulator-hemochromatosis can result in progressive iron-loading and advanced hepatic fibrosis in some individuals. We studied total body and hepatic iron loading to determine whether the distribution of iron-loading influences the risk of advanced fibrosis. Methods: One hundred thirty-eight men and 66 women with hemochromatosis who underwent liver biopsy for staging of hepatic fibrosis had evaluation of hepatic iron concentration (HIC), hepatic iron index (HIC/age), total body iron stores (mobilizable iron), and mobilizable iron/HIC ratio (a marker of total body iron relative to hepatic iron). The potential impact of liver volume on mobilizable iron stores was assessed using magnetic resonance imaging in a separate cohort of 19 newly diagnosed individuals with hemochromatosis. Results: Of 204 biopsied subjects, 41 had advanced fibrosis and exhibited 60% greater accumulation of mobilizable iron relative to HIC (mean 0.070 ± 0.008 g Fe/[μmol Fe/g]) compared with 163 subjects with low-grade fibrosis (mean 0.044 ± 0.002 g Fe/[μmol Fe/g], P < .0001). Linear regression modeling confirmed a discrete advanced hepatic fibrosis phenotype associated with greater mobilizable iron stores relative to HIC. The ratios of the upper to lower 95% limits of the distributions of liver volumes and the mobilizable iron/HIC ratios were 2.7 (95% confidence interval 2.3–3.0) and 9.7 (95% confidence interval 8.0–11.7), respectively, indicating that the distribution of liver volumes is not sufficiently wide to explain the variability in mobilizable iron/HIC ratios, suggesting that significant extrahepatic iron loading is present in those with advanced hepatic fibrosis. Conclusion: Advanced hepatic fibrosis develops in hemostatic iron regulator-hemochromatosis individuals who also have excessive extrahepatic mobilizable iron stores.

Abstract Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

Cell division presents a challenge for eukaryotic cells: how can chromosomes effectively segregate within the confines of a membranous nuclear compartment? Different organisms have evolved diverse solutions by modulating the degree of nuclear compartmentalization, ranging from complete nuclear envelope breakdown to complete maintenance of nuclear compartmentalization via nuclear envelope expansion. Many intermediate forms exist between these extremes, suggesting that nuclear dynamics during cell division are surprisingly plastic. In this review, we highlight the evolutionary diversity of nuclear divisions, focusing on two defining characteristics: (1) chromosome compartmentalization and (2) nucleocytoplasmic transport. Further, we highlight recent evidence that nuclear behavior during division can vary within different cellular contexts in the same organism. The variation observed within and between organisms underscores the dynamic evolution of nuclear divisions tailored to specific contexts and cellular requirements. In-depth investigation of diverse nuclear divisions will enhance our understanding of the nucleus, both in physiological and pathological states.

AbstractThe entrepreneurship field is increasingly interlaced with diverse disciplines, tackling complex societal issues from sustainability to digitalization and family business dynamics. Recognizing the necessity to steer future research, the editorial team of Cogent Business and Management’s Entrepreneurship and Innovation section present ten research domains identified through collective expertise. These areas, ranging from corporate innovation to entrepreneurship education and transitional entrepreneurship, are critical for academic investigation and hold potential for significant societal impact. These domains are not intended to constitute a ‘top 10’ list, nor are they exhaustive; rather, they are intended to help guide scholars toward research domains we believe are ripe for exploration and with the potential to be highly impactful. These domains embody the field’s ever-evolving nature, encapsulating the entrepreneurial spirit as a quilt of interconnected patches rather than isolated pieces. They encourage an interdisciplinary approach, highlighting the need for a comprehensive understanding of entrepreneurial activity. As the entrepreneurship literature grows, its adaptability will be crucial for theoretical advancement and practical applications. The proposed research roadmap aims to ignite cross-disciplinary dialogue, driving the impact of entrepreneurship research beyond academic circles and into the realms of policy and practice.

Substantial urban expansion is expected in global biodiversity hotspots over the next decade, especially in Asia. One such hotspot is Sulawesi, Indonesia, which hosts a diverse array of wild mammals, including bats. While urbanization may threaten some bats, species are not uniformly sensitive to urbanization. Many bat species’ sensitivity to urbanization is associated with their foraging strategies (or foraging guild), but information from Asia, generally, is severely lacking. Here we address this knowledge gap regarding urban sensitivity among insectivorous, echolocating bats within the context of urban informal settlements around the city of Makassar, South Sulawesi. Globally and in Makassar, informal settlements often exist on the fringe of cities, forming an urban-undeveloped land interface. Consequently, they may present opportunities to support conservation for some bats, given a growing focus on nature-based sustainable development solutions to improve the lives of informal settlement residents. We examined how, among informal settlements across Makassar, relative activity of bat sonotypes (in lieu of taxonomic species) from different foraging guilds was related to environmental factors associated with urban expansion. We found bat activity was influenced by processes interacting across multiple spatial scales ranging from the landscape- (e.g., spatial location relative to dense development in the urban core) to local-level (e.g., particular environmental features within 500 m). Broadly, we found some foraging guilds had lower overall relative activity, as well lower activity within the urban core compared to the peri-urban zone, indicating differential sensitivity to urbanization among Makassar’s bats that matches findings elsewhere. However, intensity of both urban and peri-urban informal settlement habitat use by particular bats was driven by a combination of landscape- and local-scale features. At the local scale, tree cover and inland water area frequently influenced sonotype activity in settlements, including urban core habitat use by urban-sensitive bats. Our work demonstrates that, especially if coordinated across broader spatial scales, local nature-based upgrades in informal settlements incorporating diverse green and blue spaces have the potential to enhance suitability of urban zones for both bats and for people.

An 11-month-old girl with severe acidosis, lethargy and vomiting, was diagnosed with holocarboxylase synthetase deficiency. She received biotin and was stable until age 8 years when vomiting, severe acidosis, hypoglycemia, and hyperammonemia developed. Management with intravenous glucose aiming to stimulate anabolism led to hyperglycemic ketoacidosis. Insulin therapy rapidly corrected biochemical parameters, and clinical status improved. We propose that secondary Krebs cycle disturbances affecting pancreatic beta cells impaired glucose-stimulated insulin secretion, resulting in insulinopenia.

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1–mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

By definition, ill and injured animals are on the negative valence of animal welfare. For beef cattle kept in feedlot settings, advances in cattle health management have resulted in a greater understanding and prevention of illness and injury. However, the management of cattle once they become ill and injured is an understudied area, and there are gaps in knowledge that could inform evidence-based decision-making and strengthen welfare for this population. The aim of this review is to provide a comprehensive overview of the acquired knowledge regarding ill and injured feedlot cattle welfare, focusing on existing knowledge gaps and implications for hospital and chronic pen management and welfare assurance. Ill and injured feedlot cattle consist of acutely impaired animals with short-term health conditions that resolve with treatment and chronically impaired animals with long-term health conditions that may be difficult to treat. A literature search identified 110 articles that mentioned welfare and ill and injured feedlot cattle, but the population of interest in most of these articles was healthy cattle, not ill and injured cattle. Articles about managing ill and injured cattle in specialized hospital (n = 12) or chronic (n = 2) pens were even more sparse. Results from this literature search will be used to outline the understanding of acutely and chronically ill and injured feedlot cattle, including common dispositions and welfare considerations, behavior during convalescence, and strategies for identifying and managing ill and injured cattle. Finally, by working through specific ailments common in commercial feedlot environments, we illustrate how the Five Domains Model can be used to explore feelings and experiences and subsequent welfare state of individual ill or injured feedlot cattle. Using this approach and our knowledge of current industry practices, we identify relevant animal-based outcomes and critical research questions to strengthen knowledge in this area. A better understanding of this overlooked topic will inform future research and the development of evidence-based guidelines to help producers care for this vulnerable population.

Support for political violence in the United States appears to be growing. We outline a model that positions ingroup projection—seeing ingroup values as the shared values of a larger inclusive societal group—as a key psychological process through which identification with political ingroups (Democrats/Republicans) and with national superordinate categories (Americans) influence support for political violence. We tested this model in two studies. Study 1 (N = 297) included original survey data collected during the 2016 US Presidential election, and analyses revealed that identification with Democrats or Republicans and identification with Americans both had positive indirect effects on support for political violence that were mediated by ingroup projection. Study 2 (N = 642) provided a preregistered replication of these results using original data collected during the 2022 US Midterm Senate elections. These results provide insight into the psychological processes that underlie support for political violence in the United States and elucidate a generalizable model for understanding destructive intergroup behaviors in a variety of real-world intergroup contexts.

Abstract Hospital-acquired diarrhoea (HAD) is common, and often associated with gut microbiota and metabolome dysbiosis following antibiotic administration. Clostridioides difficile is the most significant antibiotic-associated diarrhoeal (AAD) pathogen, but less is known about the microbiota and metabolome associated with AAD and C. difficile infection (CDI) with contrasting antibiotic treatment. We characterised faecal microbiota and metabolome for 169 HAD patients (33 with CDI and 133 non-CDI) to determine dysbiosis biomarkers and gain insights into metabolic strategies C. difficile might use for gut colonisation. The specimen microbial community was analysed using 16 S rRNA gene amplicon sequencing, coupled with untargeted metabolite profiling using gas chromatography-mass spectrometry (GC-MS), and short-chain fatty acid (SCFA) profiling using GC-MS. AAD and CDI patients were associated with a spectrum of dysbiosis reflecting non-antibiotic, short-term, and extended-antibiotic treatment. Notably, extended antibiotic treatment was associated with enterococcal proliferation (mostly vancomycin-resistant Enterococcus faecium) coupled with putative biomarkers of enterococcal tyrosine decarboxylation. We also uncovered unrecognised metabolome dynamics associated with concomitant enterococcal proliferation and CDI, including biomarkers of Stickland fermentation and amino acid competition that could distinguish CDI from non–CDI patients. Here we show, candidate metabolic biomarkers for diagnostic development with possible implications for CDI and vancomycin-resistant enterococci (VRE) treatment.

The leucine catabolism pathway intermediate, trans-3-methylglutaconyl (3MGC) CoA, is considered to be the precursor of 3MGC acid, a urinary organic acid associated with specific inborn errors of metabolism (IEM). trans-3MGC CoA is an unstable molecule that can undergo a sequence of non-enzymatic chemical reactions that lead to either 3MGC acid or protein 3MGCylation. Herein, the susceptibility of trans-3MGC CoA to protein 3MGCylation was investigated. trans-3MGC CoA was generated through the activity of recombinant 3-methylcrotonyl CoA carboxylase (3MCCCase). Following enzyme incubations, reaction mixtures were spin-filtered to remove 3MCCCase. The recovered filtrates, containing trans-3MGC CoA, were then incubated in the presence of bovine serum albumin (BSA). Following this, sample aliquots were subjected to α-3MGC IgG immunoblot analysis to probe for 3MGCylated BSA. Experiments revealed a positive correlation between trans-3MGC CoA incubation temperature and 3MGCylated BSA immunoblot signal intensity. A similar correlation was observed between incubation time and 3MGCylated BSA immunoblot signal intensity. When trans-3MGC CoA hydratase (AUH) was included in incubations containing trans-3MGC CoA and BSA, 3MGCylated BSA immunoblot signal intensity decreased. Evidence that protein 3MGCylation occurs in vivo was obtained in studies with liver-specific 3-hydroxy-3-methylglutaryl (HMG) CoA lyase knockout mice. Therefore, trans-3MGC CoA is a reactive, potentially toxic metabolite, and under normal physiological conditions, lowering trans-3MGC CoA levels via AUH-mediated hydration to HMG CoA protects against aberrant non-enzymatic chemical reactions that lead to protein 3MGCylation and 3MGC acid production.

While genotoxic chemotherapeutic agents are among the most effective tools to combat cancer, they are often associated with severe adverse effects caused by indiscriminate DNA damage in non-tumor tissue as well as increased risk of secondary carcinogenesis. This study builds on our previous work demonstrating that the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 elicits a non-canonical DNA damage response and our discovery of a critical role for Topoisomerase 2α (Top2α) in the initiation of Pol I-dependent transcription. Here, we identify Top2α as a mediator of CX-5461 response in the murine Eµ-Myc B lymphoma model whereby sensitivity to CX-5461 is dependent on cellular Top2α expression/activity. Most strikingly, and in contrast to canonical Top2α poisons, we found that the Top2α-dependent DNA damage induced by CX-5461 is preferentially localized at the ribosomal DNA (rDNA) promoter region, thereby highlighting CX-5461 as a loci-specific DNA damaging agent. This mechanism underpins the efficacy of CX-5461 against certain types of cancer and can be used to develop effective non-genotoxic anticancer drugs.

Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development Goals previously identified childhood blindness as a key issue in the twentieth century, and while public health measures are underway, the precise etiologies and management require ongoing investigation and care, particularly within resource-limited settings such as sub-Saharan Africa. We systematically reviewed the literature on childhood blindness in West Africa to identify the anatomic classification and etiologies, particularly those causes of childhood blindness with systemic health implications. Treatable causes included cataract, refractive error, and corneal disease. Systemic etiologies identified included measles, rubella, vitamin A deficiency, and Ebola virus disease. While prior public health measures including vitamin A supplementation and vaccination programs have been deployed in most countries with reported data, multiple studies reported preventable or reversible etiologies of blindness and vision impairment. Ongoing research is necessary to standardize reporting for anatomies and/or etiologies of childhood blindness to determine the necessity of further development and implementation of public health measures that would ameliorate childhood blindness and vision impairment.

Recently, Clarke et al. published a study using spinal cord susceptibility weighted imaging in multiple sclerosis patients at 7T. They discovered dilated intradural extramedullary veins surrounding the cord. The purpose of this commentary is to point out some recent research by our group, which suggests this dilatation also occurs in the bridging cortical veins surrounding the brain. The dilatation indicates a focal elevation in the venous pressure secondary to impedance mismatching. Due to the shared outflow geometry, dilatation of the outflow veins will obstruct the glymphatic pathway of the spinal cord altering the immune response.

The underrepresentation of the female population in exercise sciences could be attributed, at least in part, to difficulty in appropriately accounting for the effects of the menstrual cycle (MC). Previous studies examining the effects of the MC on aerobic performance and subjective measures of aerobic performance show conflicting results.Purpose: The study examined how the MC affects the objective and subjective measures of aerobic performance within untrained female participants and in comparison with untrained male participants assessed at similar time intervals.Methods: Twenty-one participants (12 females and 9 males) completed a graded exercise test (GXT) on a cycle ergometer. The female participants were tested during their early follicular (EF; menses), ovulatory (O), and mid-luteal (ML) phases of the MC. The male participants were included as the control group and were randomly assigned to a menstrual cycle phase for each visit. During GXT, maximal oxygen consumption (VO2max), respiratory exchange ratio (RER), maximal heart rate (HRmax), peak blood lactate, and rating of perceived exertion (RPE) were determined. Twenty-four hours post-exercise, the perceived recovery status (PRS) was assessed. The MC phase was estimated using basal body temperature (BBT) in the female participants.Results: The male participants obtained a higher peak power and VO2max compared to the female participants (p < 0.05). All objective measures of aerobic performance did not significantly differ across the MC phases or time points that were tested. In the untrained female participants, an effect of the MC phase on RPE was found, with RPE being higher at EF (8.92 ± 0.79) compared to O (7.67 ± 1.23; p < 0.05) and ML (7.75 ± 1.06; p < 0.05). In addition, an effect of the MC phase on PRS was found, with perceived recovery being lower at EF (6.83 ± 0.94) compared to O (8.83 ± 1.12) and ML (8.67 ± 0.65; all p < 0.005) for the untrained female participants. No significant differences in RPE and PRS were found between tests in the untrained male participants. The female participants had lower perceived recovery following EF (6.83 ± 0.94) compared with the male participants (9.00 ± 1.00; p < 0.001).Conclusion: The untrained female participants perceived greater exertion during GXT and impaired recovery following GXT in EF compared to O and ML. These results may be attributed to either a drop in female sex hormone concentrations or discomfort associated with menses. The male participants did not exhibit any changes over time. Future studies using subjective parameters such as perceived exertion to track the internal load of training in the naturally menstruating female population should consider menses.

IntroductionA health and lifestyle advisor service embedded within primary care was piloted in Kingston-upon-Hull from January 2021. We aimed to evaluate the first two years of service delivery by identifying patient demographics referred to the service, reason for referral, determine uptake and retention rates, and monitor individual lifestyle-related risk factor changes following discharge.MethodsAnonymised data were extracted from the SystmOne database for all patients referred to the service between January 2021 and January 2023.ResultsIn the initial two years of the service, 705 unique patients were referred at a mean rate of ∼29 per month. Each unique patient received a median (robust median absolute deviation; [MAD]) of 3 (Steel N, et al 2018) planned consultations prior to discharge over this period. The majority of referrals were for symptom management and health promotion purposes (95%). Of those referred, 69% attended their appointments, and 14% did not attend. The majority of referrals were white British (55%), however, the service did receive a substantial number of referrals from minority ethnic groups, with only 67% of referrals speaking English as their main language. Eighteen distinct languages were spoken. Most referrals were classified as class I obese (59.4%). Across initial and final appointments, median (robust MAD) systolic blood pressure was 130 (15) mmHg and 130 (15) mmHg, and median (robust MAD) waist circumference was 103.0 (13.3) cm and 101.0 (13.3) cm.ConclusionThe evaluation highlighted the demand for this service embedded within primary care settings in Kingston-upon-Hull. Service engagement was evident, and a large proportion of those who engaged were from minority ethnic groups. A high proportion of referrals presented with obesity and/or hypertension which requires further investigation.

Multiple studies report that melanomas are innervated tumors with sensory and sympathetic fibers where these neural fibers play crucial functional roles in tumor growth and metastasis with branch specificity. Yet there is no study which reports the direct neural recording and its pattern during in-vivo progression of the cancer. We performed daily neural recordings from male and female mice bearing orthotopic metastasizing- melanomas and melanomas with low metastatic poential, derived from B16-F10 and B16-F1 cells, respectively. Further, to explore the origins of neural activity, 6-Hydroxidopamine mediated chemical sympathectomy was performed followed by daily microneurographic recordings. We also performed the daily bioluminescent imaging to track in vivo growth of primary tumors and distant metastasis to the cranial area. Our results show that metastasizing tumors display high levels of neural activity while tumors with low metastatic potential lack it indicating that the presence of neural activity is linked to the metastasizing potential of the tumors. Moreover, the neural activity is not continuous over the tumor progression and has a sex-specific temporal patterns where males have two peaks of high neural activity while females show a single peak. The neural peak activity originated in peripheral sympathetic nerves as sympathectomy completely eliminated the peak activity in both sexes. Peak activities were highly correlated with the distant metastasis in both sexes. These results show that sympathetic neural activity is crucially involved in tumor metastasis and has sex-specific role in malignancy initiation.

As technology continues to evolve, the possibility for a wide range of dangers to people, organizations, and countries escalate globally. The United States federal government classifies types of threats with the capability of inflicting mass casualties and societal disruption as Chemical, Biological, Radiological, Nuclear, and Energetics/Explosives (CBRNE). Such incidents encompass accidental and intentional events ranging from weapons of mass destruction and bioterrorism to fires or spills involving hazardous or radiologic material. All of these have the capacity to inflict death or severe physical, neurological, and/or sensorial disabilities if injuries are not diagnosed and treated in a timely manner. Ophthalmic injury can provide important insight into understanding and treating patients impacted by CBRNE agents; however, improper ophthalmic management can result in suboptimal patient outcomes. This review specifically addresses the biological agents the Center for Disease Control and Prevention (CDC) deems to have the greatest capacity for bioterrorism. CBRNE biological agents, encompassing pathogens and organic toxins, are further subdivided into categories A, B, and C according to their national security threat level. In our compendium of these biological agents, we address their respective CDC category, systemic and ophthalmic manifestations, route of transmission and personal protective equipment considerations as well as pertinent vaccination and treatment guidelines.

Abstract Background The literature regarding the global cerebral blood flow (CBF) in idiopathic intracranial hypertension (IIH) is divergent leading to skepticism about the significance of blood flow to the disease’s underlying pathophysiology. Methods The purpose of the current paper is to perform a PRISMA scoping review of the literature describing the CBF in IIH. The review investigated the PUBMED and Scopus data bases looking at case mix, technique and the methodologies employed by the studies selected. Discussion Many studies indicate that the flow in IIH is normal but others show the flow to be altered. These later studies show a range of flows from a reduction of 20% to an increase of 50% compared to control values. Obesity is a common finding in IIH and is known to reduce CBF, anemia occurs in approximately 20% of IIH patients and is a potent cause of an increased CBF. Thus, variations in case mix may have a significant effect on the final outcome in those studies which are underpowered. The varying techniques which have been used to estimate CBF have differing strengths and weaknesses which may also have a bearing on the outcome. Some papers have significant confounding methodological issues. Conclusions This review suggests each of the variables investigated are responsible for the divergent CBF findings in IIH.

The ability to utilize a hybrid-photon-counting detector to its full potential can significantly influence data quality, data collection speed, as well as development of elaborate data acquisition schemes. This paper facilitates the optimal use of EIGER2 detectors by providing theory and practical advice on (i) the relation between detector design, technical specifications and operating modes, (ii) the use of corrections and calibrations, and (iii) new acquisition features: a double-gating mode, 8-bit readout mode for increasing temporal resolution, and lines region-of-interest readout mode for frame rates up to 98 kHz. Examples of the implementation and application of EIGER2 at several synchrotron sources (ESRF, PETRA III/DESY, ELETTRA, AS/ANSTO) are presented: high accuracy of high-throughput data in serial crystallography using hard X-rays; suppressing higher harmonics of undulator radiation, improving peak shapes, increasing data collection speed in powder X-ray diffraction; faster ptychography scans; and cleaner and faster pump-and-probe experiments.

Abstract Background The objective of this systematic review is to identify characteristics, trends, and gaps in measurement in Science, Technology, Engineering, and Mathematics (STEM) education research. Methods We searched across several peer-reviewed sources, including a book, similar systematic reviews, conference proceedings, one online repository, and four databases that index the major STEM education research journals. We included empirical studies that reported on psychometric development of scales developed on college/university students for the context of post-secondary STEM education in the US. We excluded studies examining scales that ask about specific content knowledge and contain less than three items. Results were synthesized using descriptive statistics. Results Our final sample included the total number of N = 82 scales across N = 72 studies. Participants in the sampled studies were majority female and White, most scales were developed in an unspecified STEM/science and engineering context, and the most frequently measured construct was attitudes. Internal structure validity emerged as the most prominent validity evidence, with exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) being the most common. Reliability evidence was dominated by internal consistency evidence in the form of Cronbach’s alpha, with other forms being scarcely reported, if at all. Discussion Limitations include only focusing on scales developed in the United States and in post-secondary contexts, limiting the scope of the systematic review. Our findings demonstrate that when developing scales for STEM education research, many types of psychometric properties, such as differential item functioning, test–retest reliability, and discriminant validity are scarcely reported. Furthermore, many scales only report internal structure validity (EFA and/or CFA) and Cronbach’s alpha, which are not enough evidence alone. We encourage researchers to look towards the full spectrum of psychometric evidence both when choosing scales to use and when developing their own. While constructs such as attitudes and disciplines such as engineering were dominant in our sample, future work can fill in the gaps by developing scales for disciplines, such as geosciences, and examine constructs, such as engagement, self-efficacy, and perceived fit.

Abstract Climate change poses an ever-increasing risk to our stone built heritage. Among conservation actions, the use of consolidant products is considered a possible response to this challenge, and the adoption of nanolimes has been widely studied showing promising results. However, while the effectiveness and method of application has been assessed, few studies have probed the changes in drying kinetics following treatment. In fact, a drastic alteration of the water transport might lead to further anomalies. This study investigates the influence of nanolimes dispersed in ethanol on the drying kinetics of Clipsham limestone using cavity ring-down spectroscopy. The degree of treatment was assessed by gravimetry, Raman spectroscopy, optical microscopy, colorimetry, optical profilometry and thin section analysis. Results showed an increase in the dry mass, observable colour changes and decrease in surface roughness. Small but reproducible increases were observed in the evaporation flux for phase I behaviour following treatment, however, no changes were observed in the total mass of water released or the phase II diffusivity. Determination of the activation energy associated with phase II drying was unchanged following treatment . These results indicate that following treatment there has been little-to-no change in the internal surfaces and structure of the stone to affect vapour transport.

Abstract Advanced hepatic fibrosis occurs in up to 25% of individuals with C282Y homozygous hemochromatosis. Our aim was to determine whether human leukocyte antigen (HLA)-A3 and B7 alleles act as genetic modifiers of the likelihood of advanced hepatic fibrosis. Between 1972 and 2013, 133 HFE C282Y homozygous individuals underwent clinical and biochemical evaluation, HLA typing, liver biopsy for fibrosis staging and phlebotomy treatment. Hepatic fibrosis was graded according to Scheuer as F0–2 (low grade hepatic fibrosis), F3–4 (advanced hepatic fibrosis), and F4 cirrhosis. We analysed associations between the severity of fibrosis and HLA-A3 homozygosity, heterozygosity or absence, with or without the presence of HLA-B7 using categorical analysis. The mean age of HLA-A3 homozygotes (n = 24), heterozygotes (n = 65) and HLA-A3 null individuals (n = 44) was 40 years. There were no significant differences between the groups for mean(± SEM) serum ferritin levels (1320 ± 296, 1217 ± 124, 1348 ± 188 $$\upmu$$ μ g/L), hepatic iron concentration (178 ± 26, 213 ± 22, 199 ± 29 $$\upmu$$ μ mol/g), mobilizable iron stores (9.9 ± 1.5, 9.5 ± 1.5, 11.5 ± 1.7 g iron removed via phlebotomy), frequency of advanced hepatic fibrosis (5/24[12%], 13/63[19%], 10/42[19%]) or cirrhosis (3/24[21%], 12/63[21%], 4/42[24%]), respectively. The presence or absence of HLA-B7 did not influence the outcome. Thus, HLA-A3 and HLA-B7 alleles are not associated with the risk of advanced hepatic fibrosis or cirrhosis in C282Y hemochromatosis.

Abstract Sound exerts wide‐ranging influence on humans. The quality of that influence depends on the sound source and context in which it is perceived, but nature sounds are generally preferred by people and associated with health and well‐being benefits. In many environments, sounds are highly mixed giving rise to a multi‐source ‘soundscape’ that may vary through days or seasons. The complex and dynamic nature of soundscapes makes them challenging to quantify or classify to rigorously compare them and their contributing sources quantitatively through space and time. We address this challenge by developing an analytical procedure resulting in a generalized soundscape classification framework that (i) elucidates dominant sound sources (e.g. biophony vs. anthrophony) and (ii) can be used to improve our understanding of spatial and temporal variation in soundscapes across different contexts. We also address a knowledge gap in urban sound research by describing the soundscapes of urban informal settlements in Fiji and Indonesia. Despite the growing emphasis on improving the physical design and quality of life in urban informal settlements, little is known about soundscapes in these settings or their relationship to human health and well‐being. We identified seven soundscape classes representing relative dominance by (i) sustained geophony, biophony dominated by (ii) insect stridulation or (iii) bird song, anthrophony dominated by (iv) machines, (v) vehicles, (vi) human voices or (vii) a mixture of the former. These classes were applicable in both Indonesia and Fiji but differed in their prevalence between the countries, times of day and seasons in expected ways. Future automatic sorting of new sound data into this classification framework is provided by a supervised classification model that attained an overall testing accuracy of 94% and Cohen's kappa of 0.93. Our procedure yields broadly applicable, informative soundscape classes indicative of dominant sound sources, including natural sounds, that are known to have different effects on human health. Therefore, our soundscape classification framework can be used in conjunction with health, well‐being, or economic data, to aid the development, assessment and scaling of sustainable design solutions for liveable cities and especially for improving urban informal settlement environments. Read the free Plain Language Summary for this article on the Journal blog.

Humanising pedagogy has been a focus of recent research as more universities move to online and blended models of instruction. Online learning has been linked to feelings of isolation, disconnection, and depersonalisation of the learning experience for many students. In South Africa, the shift to online instruction took place in the context of the Covid-19 pandemic and recent student movements that brought attention to how the country’s violent history resulted in structural inequalities in terms of race and class that affect learning environments. Thus, humanising pedagogy also meant recognising and addressing how students’ contextual challenges might affect their feelings of connection in the learning environment. In this article, we present a case study of a first-year course at a South African university where we used online discussion forums that required students to engage with weekly forum tasks. Through thematic content analysis of students’ dialogic responses on these forum tasks, we demonstrate how the tasks facilitated humanising pedagogy by allowing students to use their authentic voices, to form social connections, and to reflect their affective and personal experiences. We argue that interactive, asynchronous online forums can be effective tools to facilitate humanising online pedagogy when these forums are designed in ways that encourage dialogic learning, use content that is relevant to students’ contexts, and give students agency by allowing them to select texts for discussion and share their diverse perspectives. Our analysis also showed limitations to forum discussions which include students echoing responses and instances of silencing and unsupportive group dynamics.

Abstract Surface deformation plays a key role in illuminating magma transport at active volcanoes, however, unambiguous separation of deep and shallow transport remains elusive. The Socorro Magma Body (SMB) lacks an upper crustal magma transport system, allowing us to link geodetic measurements with predictions of numerical models investigating rheologic heterogeneities and magma‐mush interaction in the mid‐/lower crust. New InSAR observations confirm that a pattern of central surface uplift surrounded by a region of subsidence (previously coined “sombrero” deformation) has persisted over >100 years at the SMB. Our models suggest this pattern may reflect the presence of a large (>100 km width), weaker‐than‐ambient, compliant region (CR) surrounding the mid‐crustal magma body. Interactions between a pressurizing (e.g., due to melt injection and/or volatile exsolution) sill‐like magma body and CR drive the sombrero pattern, depending on both viscoelastic relaxation and pressurization timescales, explaining its rare observation and transient nature.

Abstract Iron garnets that combine robust perpendicular magnetic anisotropy (PMA) with low Gilbert damping are desirable for studies of magnetization dynamics as well as spintronic device development. This paper reports the magnetic properties of low‐damping bismuth‐substituted iron garnet thin films (Bi0.8Y2.2Fe5O12) grown on a series of single‐crystal gallium garnet substrates. The anisotropy is dominated by magnetoelastic and growth‐induced contributions. Both stripe and triangular domains form during field cycling of PMA films, with triangular domains evident in films with higher PMA. Ferromagnetic resonance measurements show damping as low as 1.3 × 10−4 with linewidths of 2.7 to 5.0 mT. The lower bound for the spin‐mixing conductance of BiYIG/Pt bilayers is similar to that of other iron garnet/Pt bilayers.

Chemical agents have been utilized for centuries in warfare and pose a health threat to civilians and military personnel during armed conflict. Despite treaties and regulations against their use, chemical agent exposure remains a threat and measures to understand their effects and countermeasures for systemic and organ-specific health are needed. Many of these agents have ocular complications, both acute and chronic. This mini-review focuses on key chemical agents including vesicants (mustards, lewisite), nerve agents (sarin, VX), knockdown gasses (hydrogen cyanide), and caustics (hydrofluoric acid). Their ophthalmic manifestations and appropriate treatment are emphasized. Acute interventions include removal of the source and meticulous decontamination, as well as normalization of pH to 7.2–7.4 if alteration of the ocular pH is observed. Besides vigorous lavage, acute therapies may include topical corticosteroids and non-steroid anti-inflammatory therapies. Appropriate personal protective equipment (PPE) and strict donning and doffing protocols to avoid healthcare provider exposure are also paramount in the acute setting. For more severe disease, corneal transplantation, amniotic membrane graft, and limbal stem cell transplantation may be needed. Orbital surgery may be required in patients in whom cicatricial changes of the ocular surface have developed, leading to eyelid malposition. Multidisciplinary care teams are often required to handle the full spectrum of findings and consequences associated with emerging chemical threats.

Yucatec Spanish displays a type of sentence that appears to mix elements of an active impersonal and a passive. For example, “te castigaron por mi tío” may be interpreted as “you were punished by my uncle”, where a by-phrase headed by the preposition por introduces an agent rather than a cause or reason. The verb has active morphology—it is always third-person plural, and accusative clitics (e.g., te) and DOM-marked objects are possible. This type of sentence, which I descriptively label an active–passive (A-P) hybrid, has been mentioned in previous literature on contact varieties in Mayan-speaking regions of Mexico and Guatemala, but it has not been precisely described or analyzed formally. I argue that A-P hybrid constructions are instances of grammatical object passives. Grammatical object passives have certain active properties—accusative case is assigned to a theme argument and the morphology of the verb is active, but like passives, they require that the expression of the agent be a by-phrase rather than a grammatical subject. I claim that this is possible in this variety of Spanish due to the emergence of a null pronoun, absent in other varieties of Spanish, that can merge in the specifier of Voice and restrict, rather than saturate, an agent argument, permitting the subsequent addition of a third-person by-phrase. I demonstrate that this analysis is able to explain its hybrid properties as well as other person restrictions on the by-phrases that express the agent. Finally, I describe avenues of future research that will help discern the role that language contact may have played in the emergence of A-P hybrids.

A comprehensive aircraft survey of onshore oil and gas infrastructure in British Columbia finds that methane emissions may be 1.7 times higher than the official inventory and introduces a framework for compiling measurement-led regional greenhouse gas emissions data.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

There is a lack of cost-effective, environmentally-friendly tools available to manage marine biofouling accumulation on static artificial structures such as drilling rigs, wind turbines, marine farms, and port and marina infrastructure. For there to be uptake and refinement of tools, emerging technologies need to be tested and proven at an operational scale. This study aimed to see whether biofouling accumulation could be suppressed on marine infrastructure under real-world conditions through the delivery of continuous bubble streams. Submerged surfaces of a floating marina pontoon were cleaned in-situ by divers, and the subsequent colonisation by biofouling organisms was monitored on treated (bubbles applied) and untreated sections. Continuous bubble streams proved highly effective (>95%) in controlling macrofouling accumulation on the underside surface of the marina pontoon for the first 2 months after deployment, but efficacy dropped off rapidly once bubble stream delivery was partially obscured due to biofouling accumulation on the diffuser itself. Although extensive macrofouling cover by mussels, bryozoans and hydroids was observed on treated surfaces by 4 months (27.5%, SE = 4.8%), biofouling % cover and diversity was significantly higher on untreated surfaces (79.6%, SE = 2.9%). While this study demonstrates that continuous bubble streams greatly restrict biofouling accumulation over short-to-medium timescales, improved system design, especially the incorporation of diffusers resistant to fouling, is needed for the approach to be considered a viable long-term option for biofouling management on static artificial structures.

Purpose To assess how resident and attending ophthalmologists perceive and evaluate ethically controversial scenarios regarding mentorship, authorship, and ethics compliance that may occur during research involving residents.

Abstract Rationale The effectiveness of universal immunisation with pneumococcal conjugate vaccine (PCV) has been evident in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in several countries. Reducing the cost of PCV programmes may facilitate vaccine introduction in some countries and improve the sustainability of PCV in EPIs in low-income countries when they transition away from subsidised vaccine supply. Methods and design PVS is a real-world field trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. the alternative ‘1+1’ schedule) compared to the standard schedule of three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. the standard ‘3+0’ schedule). Delivery of the interventions began in late 2019 in 68 geographic clusters and will continue for 4 years. The primary endpoint is the prevalence of nasopharyngeal vaccine-type pneumococcal carriage in children aged 2–260 weeks with clinical pneumonia in year 4. Secondary endpoints are the prevalence of vaccine-type pneumococcal carriage among all ages in year 4 and the incidence of radiological pneumonia in children enrolled to receive the interventions. Additional disease and carriage endpoints are included. Purpose This statistical analysis plan (SAP) describes the cohorts and populations, and follow-up criteria, to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe how analyses will account for the effect of clustering and stratified randomisation. The SAP defines the approach to non-inferiority and other analyses. Defining the SAP early in the trial will avoid bias in analyses that may arise from prior knowledge of trial findings.

Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.

In October 2022, New Brunswick Minister of Education and Early Childhood Development Dominic Cardy publicly resigned and widely disclosed his disappointment with Premier Blaine Higgs' leadership. Using Cardy's unprecedented public resignation letter as a primary source, this paper explores the inner workings of neoliberal governance and privatization in public education and critically analyzes data manipulation, governance shifts, and problematic conservative "hands-offism." Applying a rhizomatic methodological framing and theoretically drawing from Bourdieu and Passeron's (1977) conceptualization of symbolic violence and Gilmore's (2008) notion of "organized abandonment," we argue that neoliberal governance and privatization disproportionately affect vulnerable communities and weaken democratic processes. To understand these complexities, we utilize a rhizomatic analysis, simultaneously considering historical and geographical contexts, governance structures, and political narratives. We conclude that neoliberal governance and privatization are inherently symbolically violent, as they are used in tandem to perpetually defund and dismantle public institutions.