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Abstract Resonant inelastic x-ray scattering (RIXS) is a widely used spectroscopic technique, providing access to the electronic structure and dynamics of atoms, molecules, and solids. However, RIXS requires a narrow bandwidth x-ray probe to achieve high spectral resolution. The challenges in delivering an energetic monochromated beam from an x-ray free electron laser (XFEL) thus limit its use in few-shot experiments, including for the study of high energy density systems. Here we demonstrate that by correlating the measurements of the self-amplified spontaneous emission (SASE) spectrum of an XFEL with the RIXS signal, using a dynamic kernel deconvolution with a neural surrogate, we can achieve electronic structure resolutions substantially higher than those normally afforded by the bandwidth of the incoming x-ray beam. We further show how this technique allows us to discriminate between the valence structures of Fe and Fe2O3, and provides access to temperature measurements as well as M-shell binding energies estimates in warm-dense Fe compounds.

Abstract Background Control of humeral torsion can present a challenge, especially intraoperatively during closed reduction and fixation of humeral shaft fractures or 2-part surgical neck fractures of the proximal humerus. The objective of this study is to develop and validate an indirect method for the assessment of humeral torsion using an index that is linearly correlated with rotational arm position and can be derived from only a single plain radiographic image of the proximal humerus. Methods The Humeral Head Offset Index (HHOI) is calculated as the ratio of the medial and lateral offset of the humeral head measured from the outer cortices of the shaft on a plain radiographic or fluoroscopic image. The relationship of HHOI with humeral torsion was first verified on a sawbone model with radiopaque characteristics under fluoroscopic control. Different degrees of retroversion were simulated through manual rotation of the humerus with a digital protractor in 5° increments until 40° internally rotated and then in 5° increments until 40° externally rotated from the neutral position. The same procedure was subsequently performed digitally on Digitally Reconstructed Radiographs (DRRs) from computed tomography (CT) dataset of the sawbone. Next, the HHOI index was applied to eight randomly selected patients with total humerus CT using the same method. Spearman’s rho was calculated for the bivariate analysis of correlation between the simulated degree of retroversion and the HHOI. Strength of correlation was classified according to Koo and Li. Interrater and intrarater reliability of three blinded observers with repetition of measurement after three months were analyzed by assessing the intraclass correlation coefficient (ICC). Results Both in the sawbone model and in DRRs, we demonstrated a high to very high significant linear correlation between simulated retroversion and the HHOI. ICC values demonstrated excellent interrater reliability and excellent intrarater reliability for measurement of the HHOI. Conclusions The HHOI is a new, simple, reliable index that has a linear relationship to the rotation of the humerus and can therefore allow an indirect control of humeral torsion in comparison to the contralateral side.

Abstract The bigmouth buffalo Ictiobus cyprinellus (Catostomidae) is a freshwater fish native to North America that is known for its longevity. During the 1970s, the bigmouth buffalo was recorded as declining in Canada, Minnesota, and North Dakota and became a protected species in Canada. In the USA, population declines are exacerbated by wasteful recreational bowfishing, lack of fisheries management, and overall lack of knowledge. However, recent studies have revealed the exceptional lifespan of bigmouth buffalo, their negligible senescence, slow growth, delayed maturity, and episodic recruitment. Yet little is known about the spawning phenology of bigmouth buffalo, nor their age demographics in east central Minnesota. In this 2021–2023 study of bigmouth buffalo from Rice Lake National Wildlife Refuge we found that 99.7% (389 of 390) of the extant population hatched prior to 1972 despite annual spawning in Rice Lake. Moreover, recruitment success declined significantly since water control measures were established (1953). We found males arrive to spawning grounds with females but depart later, that both the midpoint and duration of spawn significantly vary across years, and that more massive females of the same age range invest disproportionately more in ovaries. Extensive post-spawn seining revealed bigmouth buffalo young-of-the-year in low numbers, but by mid-to-late summer they were no longer evident having likely succumbed to predation. Overall, these findings thoroughly reveal one of the oldest populations of vertebrate currently known (median age of 79 years as of 2024) and expose the stark vulnerability of a bigmouth buffalo population for which substantial recruitment has not occurred for more than six decades. Multiple lines of evidence indicate that the long-lived bigmouth buffalo is vulnerable, that a precautionary approach is immediately needed, and that the unlimited and unregulated kill-fishery be closed.

Abstract Computational fluid dynamics is an essential tool for accelerating the discovery and adoption of transformative designs across multiple engineering disciplines. Despite its many successes, no single approach consistently achieves high accuracy for all flow phenomena of interest, primarily due to limitations in the modeling assumptions. Here, we introduce a closure model for wall-modeled large-eddy simulation to address this challenge. The model, referred to as the Building-block Flow Model (BFM), rests on the premise that a finite collection of simple flows encapsulates the essential missing physics necessary to predict more complex scenarios. The BFM is designed to: (1) predict multiple flow regimes, (2) unify the closure model at solid boundaries and the rest of the flow, (3) ensure consistency with numerical schemes and gridding strategies by accounting for numerical errors, (4) be directly applicable to arbitrary complex geometries, and (5) be scalable to model additional flow physics in the future. The BFM is utilized to predict key quantities in five cases, including an aircraft in landing configuration, demonstrating similar or superior capabilities compared to previous state-of-the-art models. The design of BFM opens up new opportunities for developing closure models that can accurately represent various flow physics across different scenarios.

Abstract Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs.

This article presents an interdisciplinary theory on the causes of crime in Samoa. The theory utilises a cultural practice of building the foundation - fa’avae - of a Samoan house, to explain the causes of crime and to articulate a crime prevention strategy from the nuances of the word fa’avae. The interdisciplinary nature of this theory considers two main aspects of the Samoan life of God and family (aiga) to describe both the causes of crime in Samoa, and a way forward to restore aiga and community fractured by crime. The theory calls upon the church through church ministers – faifeau – to become active in the public sphere. This entails speaking out about the causes of crime and working in collaboration with other stakeholders in devising culturally appropriate crime prevention approaches for Samoa, likely to also be familiar to other ‘South’ Pacific nations.

Abstract Introduction Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab. Methods We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12 months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or

Abstract Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

Background: Some voxels may alter the tractography results due to unintentional alteration of noises and other unwanted factors.Objective: This study aimed to investigate the effect of local phase features on tractography results providing data are mixed by a Gaussian or random distribution noise.Material and Methods: In this simulation study, a mask was firstly designed based on the local phase features to decrease false-negative and -positive tractography results. The local phase features are calculated according to the local structures of images, which can be zero-dimensional, meaning just one point (equivalent to noise in tractography algorithm), a line (equivalent to a simple fiber), or an edge (equivalent to structures more complex than a simple fiber). A digital phantom evaluated the feasibility current model with the maximum complexities of configurations in fibers, including crossing fibers. In this paper, the diffusion images were mixed separately by a Gaussian or random distribution noise in 2 forms: a zero-mean noise and a noise with a mean of data.Results: The local mask eliminates the pixels of unfitted values with the main structures of images, due to noise or other interferer factors. Conclusion: The local phase features of diffusion images are an innovative solution to determine principal diffusion directions.

Abstract Background Studies indicate that the children of mothers who have eating disorders are at an increased risk of developing eating disorders themselves. The aim of this qualitative study was to broaden and extend current understandings of the experiences of mothers with eating disorders. The present report focuses on maternal perspectives, experiences, and support needs in relation to the intergenerational transmission of eating disorders. Method Semi-structured online interviews were conducted with parents living in the UK, USA, and Australia. Participants were eighteen mothers with a self-reported lifetime diagnosis of one or more eating disorders, who had experienced symptoms since becoming a parent, and who had at least one child aged 2 years or older. Data were analysed using reflexive thematic analysis. Results Four major themes relating to the impacts of having an eating disorder on children and intergenerational transmission were identified. These were: impacts (maternal perspectives on the ways having an eating disorder impacted their children, and their reflections around having been impacted by their own parents); breaking the cycle (strategies employed by mothers in efforts to prevent their children developing eating disorders of their own); communicating about the eating disorder (maternal experiences around disclosing or not disclosing having an eating disorder to their children); and support needs (maternal and perceived familial support needs in relation to breaking cycles of intergenerational transmission). Conclusions For mothers with eating disorders, concerns about the potential impacts on their children and fears about intergenerational transmission are salient, and these may vary for children at different ages. The mothers who participated in our study described engaging in a number of conscious strategies in efforts to manage the risks of eating disorder development in their children, but implementing these strategies was not without challenges. Implications for preventative programs to reduce the intergenerational transmission of eating disorders are discussed.

Abstract The phenomenon of BCJ duality implies that gauge theories possess an abstract kinematic algebra, mirroring the non-abelian Lie algebra underlying the colour information. Although the nature of the kinematic algebra is known in certain cases, a full understanding is missing for arbitrary non-abelian gauge theories, such that one typically works outwards from well-known examples. In this paper, we pursue an orthogonal approach, and argue that simpler abelian gauge theories can be used as a testing ground for clarifying our understanding of kinematic algebras. We first describe how classes of abelian gauge fields are associated with well-defined subalgebras of the diffeomorphism algebra. By considering certain special subalgebras, we show that one may construct interacting theories, whose kinematic algebras are inherited from those already appearing in a related abelian theory. Known properties of (anti-)self-dual Yang-Mills theory arise in this way, but so do new generalisations, including self-dual electromagnetism coupled to scalar matter. Furthermore, a recently obtained non-abelian generalisation of the Navier-Stokes equation fits into a similar scheme, as does Chern-Simons theory. Our results provide useful input to further conceptual studies of kinematic algebras.

Abstract Background Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated. Methods During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs). Results Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium and S. mattheei ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni and possible S. haematobium-S. mattheei hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis and other STIs. Conclusion Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated.

Abstract Bacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) systems recognise and methylate 6 bp non-palindromic motifs within the host genome, and prevent replication of non-methylated phage DNA that encodes these same motifs. How BREX recognises cognate motifs has not been fully understood. In this study we characterise BREX from pathogenic Salmonella and present X-ray crystallographic structures of the conserved BREX protein, PglX. The PglX N-terminal domain encodes the methyltransferase, whereas the C-terminal domain is for motif recognition. We also present the structure of PglX bound to the phage-derived DNA mimic, Ocr, an inhibitor of BREX activity. Our analyses propose modes for DNA-binding by PglX and indicate that both methyltransferase activity and defence require larger BREX complexes. Through rational engineering of PglX we broaden both the range of phages targeted, and the host motif sequences that are methylated by BREX. Our data demonstrate that PglX is used to recognise specific DNA sequences for BREX activity, contributing to motif recognition for both phage defence and host methylation.

Abstract Background The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes. Methods IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those. Results In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS. Conclusions Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

Abstract Background Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health concern as they can cause serious illness and outbreaks. In England, STEC incidence is highest among children and guidance recommends that children under six diagnosed with STEC are excluded from childcare until two consecutive stool cultures are negative. We aimed to describe the barriers and facilitators to implementing exclusion and the impact of exclusion policies on young children and their families. Methods Individual level data was obtained from a wider study focusing on shedding duration among STEC cases aged

Abstract Pure red cell aplasia (PRCA) is characterised by normocytic normochromic anaemia, reticulocytopenia and reduced erythroid precursors in bone marrow. PRCA as an immune‐related adverse event secondary to immune checkpoint inhibitor (ICI) therapy is rare. Steroids are usually used first line to treat ICI‐induced PRCA. Here, we report a case of ICI‐induced PRCA with no response to steroids but where intravenous (IV) immunoglobulin was successfully used second line. ICI therapy was reinitiated following PRCA resolution. PRCA recurrence did not occur.

Abstract Background Despite impressive improvements in the safety profile of Transcatheter aortic valve replacement (TAVR), the risk for peri-procedural stroke after TAVR has not declined substantially. In an effort to reduce periprocedural stroke, cerebral embolic protection (CEP) devices have been utilized but have yet to demonstrate benefit in all-comers. There is a paucity of data supporting the utilization of CEP in TAVR patients with an anticipated high risk for peri-procedural stroke. Methods The Transcatheter Aortic Valve Replacement In-Hospital Stroke (TASK) score is a clinical risk tool for predicting the in-hospital stroke risk of patients undergoing transfemoral TAVR. This score was used to identify high-risk patients and calculate the expected in-hospital stroke risk. This was a single-centre cohort study in all consecutive TAVR patients who had placement of CEP. The observed versus expected ratio for peri-procedural stroke was calculated. To obtain 95% credible intervals, we used 1000 bootstrapped samples of the original cohort sample size without replacement and recalculated the TASK predicted scores. Results The study included 103 patients. The median age was 83 (IQR 78,89). 63 were male (61.1%) and 45 (43.69%) had a history of previous Stroke or TIA. Two patients had an in-hospital stroke after TAVR (1.94%). The expected risk of in-hospital stroke based on the TASK score was 3.39% (95% CI 3.07–3.73). The observed versus expected ratio was 0.57 (95% CI 0.52–0.64). Conclusion In this single-center study, we found that in patients undergoing TAVR with high stroke risk, CEP reduced the in-hospital stroke risk by 43% when compared with the risk-score predicted rate. Clinical trial number N/A.

Abstract Background The plasma metabolome reflects the physiological state of various biological processes and can serve as a proxy for disease risk. Plasma metabolite variation, influenced by genetic and epigenetic mechanisms, can also affect the cellular microenvironment and blood cell epigenetics. The interplay between the plasma metabolome and the blood cell epigenome remains elusive. In this study, we performed an epigenome-wide association study (EWAS) of 1183 plasma metabolites in 693 participants from the LifeLines-DEEP cohort and investigated the causal relationships in DNA methylation–metabolite associations using bidirectional Mendelian randomization and mediation analysis. Results After rigorously adjusting for potential confounders, including genetics, we identified five robust associations between two plasma metabolites (l-serine and glycine) and three CpG sites located in two independent genomic regions (cg14476101 and cg16246545 in PHGDH and cg02711608 in SLC1A5) at a false discovery rate of less than 0.05. Further analysis revealed a complex bidirectional relationship between plasma glycine/serine levels and DNA methylation. Moreover, we observed a strong mediating role of DNA methylation in the effect of glycine/serine on the expression of their metabolism/transport genes, with the proportion of the mediated effect ranging from 11.8 to 54.3%. This result was also replicated in an independent population-based cohort, the Rotterdam Study. To validate our findings, we conducted in vitro cell studies which confirmed the mediating role of DNA methylation in the regulation of PHGDH gene expression. Conclusions Our findings reveal a potential feedback mechanism in which glycine and serine regulate gene expression through DNA methylation.

Abstract The eating and feeding disorder section of the Diagnostic and Statistical Manual of Mental Disorders 5 Text Revision (DSM-5-TR) is organized by a diagnostic algorithm that limits the contemporaneous assignment of multiple eating disorder diagnoses. Avoidant/restrictive food intake disorder (ARFID) is a disturbance in food intake typically associated with lack of interest in food, food avoidance based on sensory characteristics, and/or fear of aversive consequences from eating. According to the DSM-5-TR, an ARFID diagnosis cannot be made when weight or shape disturbances are present, and ARFID cannot be co-diagnosed with other eating disorders characterized by these disturbances. However, emerging evidence from both clinical and lived experience contexts suggests that the co-occurrence of ARFID with multiple other types of eating disorders may be problematically invisibilized by this trumping scheme. The diagnostic criteria for ARFID can contribute to inappropriate diagnosis or exclusion from diagnosis due to excessive ambiguity and disqualification based on body image disturbance and other eating disorder pathology, even if unrelated to the food restriction or avoidance. This harmfully limits the ability of diagnostic codes to accurately describe an individual’s eating disorder symptomatology, impacting access to specialized and appropriate eating disorder care. Therefore, revision of the DSM-5-TR criteria for ARFID and removal of limitations on the diagnosis of ARFID concurrent to other full-syndrome eating disorders stands to improve identification, diagnosis, and support of the full spectrum of ARFID presentations.

Abstract Background The effects of environmental disturbances on livestock are often observed indirectly through the variability patterns of repeated performance records over time. Sheep are frequently exposed to diverse extensive environments but currently lack appropriate measures of resilience (or sensitivity) towards environmental disturbance. In this study, random regression models were used to analyse repeated records of the fibre diameter of wool taken along the wool staple (bundle of wool fibres) to investigate how the genetic and environmental variance of fibre diameter changes with different growing environments. Results A model containing a fifth, fourth and second-order Legendre polynomial applied to the fixed, additive and permanent environmental effects, respectively, was optimal for modelling fibre diameter along the wool staple. The additive genetic and permanent environmental variance both showed variability across the staple length trajectory. The ranking of sire estimated breeding values (EBV) for fibre diameter was shown to change along the staple and the genetic correlations decreased as the distance between measurements along the staple increased. This result suggests that some genotypes were potentially more resilient towards the changes in the growing environment compared to others. In addition, the eigenfunctions of the random regression model implied the ability to change the fibre diameter trajectory to reduce its variability along the wool staple. Conclusions These results show that genetic variation in fibre diameter measured along the wool staple exists and this could be used to provide greater insight into the ability to select for resilience in extensively raised sheep populations.

Abstract Background Self-directed violence (SDV) comprises both suicide and self-injury and represents a pressing problem among incarcerated persons. Negative impacts of SDV in correctional settings also extend to behavioral health clinicians (BHCs) (e.g., job turnover). Correctional SDV risk assessment and management standards include staff training as part of the comprehensive approach. The Core Competency Model for Corrections (CCM-C) is a novel, evidence-informed training program for BHCs covering both clinician self-management and clinical care skills. Methods This pilot trial is a type 3 hybrid implementation–effectiveness approach. It will employ a wait-list control sequential cross-over design. Participants (N = 50–100) will be BHCs employed by the North Carolina Department of Adult Corrections. Following stratification for years of clinical experience, BHCs will be randomly assigned to (1) a training group that receives CCM-C immediately and (2) a wait-list control receiving CCM-C approximately 6 weeks later. Electronically administrated survey evaluation will occur across baseline and two follow-up (i.e., 2 weeks after each training session) time points. Discussion The primary outcome is feasibility assessed through collaboration with a Corrections Advisory Panel and feedback from BHCs. Secondary effectiveness outcomes that will be evaluated over time include SDV-related knowledge, attitudes, stigma, and intent to use training content. We will examine a tertiary outcome, namely compassion fatigue. Clinical trial limitations and impacts are discussed. Trial registration Clinicaltrials.gov, NCT06359574. This study was registered on 04/05/2024.

Abstract Background Outreach clinics were part of efforts to maximise uptake in COVID-19 vaccination. Methods We used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed. Results 50% of 288,473 exposed citizens were white British, and 71% were aged 0–49 years. There was no evidence for an overall statistically significant increase in cumulative percentage vaccinated due to the outreach clinic at 6 weeks, with an overall pooled effect estimate of -0.07% (95% CI: -1.15%, 1.02%). The pooled estimate for increased cumulative vaccine uptake varied slightly depending on how the analysis was stratified; by ethnic group it was − 0.12% (95% CI: -0.90%, 0.66%); by age group it was − 0.06% (95% CI: -0.41%, 0.28%); and by deprivation it was 0.03% (95% CI: -0.74%, 0.79%). Conclusions Living within a mile of an outreach clinic was not associated with higher vaccine uptake. Evaluation of future outreach clinics should consider the relative importance of travel amongst other barriers to accessing vaccines.

Abstract Background Domestic and family violence (DFV) is a significant public health issue that poses a high risk to women, globally. Women experiencing DFV have higher rates of healthcare utilisation than women not experiencing DFV. Healthcare services are therefore well placed to address DFV and deliver education and awareness interventions to women. Video interventions are a strategy to deliver education to women, while overcoming barriers such as language, literacy, lack of rapport with clinician, or unwillingness to disclose. The current review will aim to further understand the characteristics, methods of evaluation, and outcomes of DFV video education interventions for perinatal women. Methods The review will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A systematic search will be conducted of the following databases: Medline, Embase, PsycINFO, PsycArticles, Scopus, and Web of Science Core Collection. Two independent reviewers will screen titles and abstracts against the inclusion criteria, followed by a full text screening of eligible articles. A third reviewer will resolve discrepancies. All study types will be included. Only studies published in English will be included. Risk of bias will be assessed using the Quality Assessment with Diverse Studies (QuADS) tool. Data will undergo an aggregate mixed method synthesis informed by The Joanna Briggs Institute, before being analysed using a thematic approach. Discussion This systematic review will provide evidence on best practice for the creation, delivery, and evaluation of DFV video interventions for women in the peripartum. Systematic review registration PROSPERO registration number CRD42023475338.

Abstract The morphology and distribution of airway tree abnormalities enable diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. Furthermore, the segmentation of a complete airway tree is challenging as the intensity, scale/size and shape of airway segments and their walls change across generations. The existing classical techniques either provide an undersegmented or oversegmented airway tree, and manual intervention is required for optimal airway tree segmentation. The recent development of deep learning methods provides a fully automatic way of segmenting airway trees; however, these methods usually require high GPU memory usage and are difficult to implement in low computational resource environments. Therefore, in this study, we propose a data-centric deep learning technique with big interpolated data, Interpolation-Split, to boost the segmentation performance of the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway segments at different scales. In terms of average segmentation performance (dice similarity coefficient, DSC), our method (A) achieves 90.55%, 89.52%, and 85.80%; (B) outperforms the baseline models by 2.89%, 3.86%, and 3.87% on average; and (C) produces maximum segmentation performance gain by 14.11%, 9.28%, and 12.70% for individual cases when (1) nnU-Net with instant normalisation and leaky ReLU; (2) nnU-Net with batch normalisation and ReLU; and (3) modified dilated U-Net are used respectively. Our proposed method outperformed the state-of-the-art airway segmentation approaches. Furthermore, our proposed technique has low RAM and GPU memory usage, and it is GPU memory-efficient and highly flexible, enabling it to be deployed on any 2D deep learning model.

Abstract Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Abstract The cell division cycle 25 phosphatases CDC25A, B and C regulate cell cycle transitions by dephosphorylating residues in the conserved glycine-rich loop of CDKs to activate their activity. Here, we present the cryo-EM structure of CDK2-cyclin A in complex with CDC25A at 2.7 Å resolution, providing a detailed structural analysis of the overall complex architecture and key protein-protein interactions that underpin this 86 kDa complex. We further identify a CDC25A C-terminal helix that is critical for complex formation. Sequence conservation analysis suggests CDK1/2-cyclin A, CDK1-cyclin B and CDK2/3-cyclin E are suitable binding partners for CDC25A, whilst CDK4/6-cyclin D complexes appear unlikely substrates. A comparative structural analysis of CDK-containing complexes also confirms the functional importance of the conserved CDK1/2 GDSEID motif. This structure improves our understanding of the roles of CDC25 phosphatases in CDK regulation and may inform the development of CDC25-targeting anticancer strategies.

Abstract Optically addressable spin defects hosted in two-dimensional van der Waals materials represent a new frontier for quantum technologies, promising to lead to a new class of ultrathin quantum sensors and simulators. Recently, hexagonal boron nitride (hBN) has been shown to host several types of optically addressable spin defects, thus offering a unique opportunity to simultaneously address and utilise various spin species in a single material. Here we demonstrate an interplay between two separate spin species within a single hBN crystal, namely S = 1 boron vacancy defects and carbon-related electron spins. We reveal the S = 1/2 character of the carbon-related defect and further demonstrate room temperature coherent control and optical readout of both S = 1 and S = 1/2 spin species. By tuning the two spin ensembles into resonance with each other, we observe cross-relaxation indicating strong inter-species dipolar coupling. We then demonstrate magnetic imaging using the S = 1/2 defects and leverage their lack of intrinsic quantization axis to probe the magnetic anisotropy of a test sample. Our results establish hBN as a versatile platform for quantum technologies in a van der Waals host at room temperature.

Abstract Introduction Intraoperative Hypotension (IOH) poses a substantial risk during surgical procedures. The integration of Artificial Intelligence (AI) in predicting IOH holds promise for enhancing detection capabilities, providing an opportunity to improve patient outcomes. This systematic review and meta analysis explores the intersection of AI and IOH prediction, addressing the crucial need for effective monitoring in surgical settings. Method A search of Pubmed, Scopus, Web of Science, and Embase was conducted. Screening involved two-phase assessments by independent reviewers, ensuring adherence to predefined PICOS criteria. Included studies focused on AI models predicting IOH in any type of surgery. Due to the high number of studies evaluating the hypotension prediction index (HPI), we conducted two sets of meta-analyses: one involving the HPI studies and one including non-HPI studies. In the HPI studies the following outcomes were analyzed: cumulative duration of IOH per patient, time weighted average of mean arterial pressure

Abstract Background A recent Lancet commission called for more research on palliative care in low- and middle-income (LMIC) countries such as Colombia. A research priority setting approach has been recommended by The Global Forum for Health Research to address the huge gap in research output between LMIC and high-income countries, with influential health service bodies recommending the active involvement of non-research expert stakeholders in establishing research priorities to address service user needs. Method Priority setting partnership (PSP) following the four stages of the James Lind Alliance methodology; establishing the partnership, identifying evidence uncertainties, refining questions and uncertainties, and prioritization. Data from MS forms were analysed using descriptive statistics. Results A total of 33 stakeholders attended an online PSP workshop and completed the Mentimeter exercise in Microsoft Teams. A total of 48 attended the subsequent in person prioritisation exercise in urban Bogota (n = 22) and rural Popayan (n = 25). The stakeholders were a diverse group of health professionals (physicians, medical students, nurses, dentists, physiotherapists, nutritionist, occupational and speech therapists), financial and administrative staff and patients with life-limiting illness and caregivers. Top research priorities included patient and caregiver needs, service provider education and training, and better integration of palliative care with cancer and non-cancer services. The key challenges included a lack of interest in palliative care research, along with funding, time and resource constraints. Key solutions included collaboration across disciplines and settings, highlighting benefits of palliative research to help secure adequate resources, and multicentre, mixed method research, with patient involvement from the research development stage. Conclusion The findings of this PSP should be disseminated among palliative care associations worldwide to inform international multicentre studies, and among governmental and nongovernmental organisations that promote research in Colombia. A focus on patient and family caregiver palliative care needs in Colombia should be prioritised.

Abstract Sinistral portal hypertension, also known as left-sided portal hypertension, is a rare cause of gastric variceal bleeding which occurs secondary to occlusion of the splenic vein. We present a case of venous occlusion and sinistral portal hypertension secondary to distal pancreatic cancer requiring treatment of gastric variceal bleeding. After failing conservative management, transvenous intervention was attempted, but a venous communication with the gastric varices was unable to be identified on multiple venograms. A percutaneous trans-splenic approach using a 21-G needle and ultrasound guidance was successful in directly accessing an intraparenchymal vein feeding the gastric varices, and glue embolization was performed directly through the access needle with excellent results.

Abstract Background Concerns about mental and cognitive health are common among university students. Engaging in regular physical exercise has been shown to enhance both mental health and cognitive performance, yet most students are not participating in the level of exercise required to obtain these benefits. The Behaviour Change Wheel (BCW) provides a framework for developing behavioural interventions that are informed by theory, evidence, and stakeholder perspectives. The current study aimed to apply the BCW to develop the PEAK Mood, Mind, and Marks program (i.e., PEAK), a behaviour change intervention designed to increase university students’ exercise engagement for the benefit of their mental and cognitive health. Methods PEAK was developed across three stages of the BCW: (1) understand the target behaviour, (2) identify intervention options, and (3) identify intervention content and delivery mode. Development was informed by triangulated data from a systematic literature review, co-design consultations with key stakeholders, and knowledge of relevant experts. Consultations with stakeholders involved focus groups with 25 university students and individual interviews with 10 university leaders and staff to identify barriers and facilitators to students’ exercise engagement and the adoption and implementation of PEAK by universities. Template analysis was used to code transcripts to the capability, opportunity, and motivation (COM-B) model of behaviour. The BCW was applied to identify the most appropriate intervention types and behaviour change techniques (BCTs). Results Thirty-one barriers and facilitators were identified and mapped to seven intervention types (Education; Modelling; Persuasion; Environmental Restructuring; Incentivisation; Training; and Enablement) and 26 BCTs, which were delivered across digital channels and in-person. The final intervention consisted of multiple components targeting students’ capability (e.g., increasing knowledge about the mental and cognitive health benefits of exercise), opportunity (e.g., providing a flexible range of accessible exercise options and social support), and motivation (e.g., increasing the perceived importance of exercise) to exercise. Conclusions University students and staff describe a need and appetite for more empowering, scalable solutions to support students’ mental and cognitive health. Exercise-based approaches that are informed by behaviour change frameworks, evidence, and stakeholder perspectives, such as PEAK, have the potential to address this need. Current findings will inform a pilot of PEAK to evaluate its efficacy and implementation.

Abstract Background Recently-updated global guidelines for cervical cancer screening incorporated new technologies—most significantly, the inclusion of HPV DNA detection as a primary screening test—but leave many implementation decisions at countries’ discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. Methods Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing “triage” approaches—i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. Results Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. Conclusions These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

Abstract Background Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. Methods We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. Results 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). Conclusions Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Abstract Background Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing. Methods The human cells from respiratory samples are lysed mechanically using 1.4 mm zirconium-silicate spheres and the human DNA is depleted using a nonspecific endonuclease. The RNA is converted to dsDNA to allow the simultaneous sequencing of DNA and RNA. Results The method decreases human DNA concentration by a median of eight Ct values while detecting a broad range of RNA & DNA viruses, bacteria, including atypical pathogens (Legionella, Chlamydia, Mycoplasma) and fungi (Candida, Pneumocystis, Aspergillus). The first automated reports are generated after 30 min sequencing from a 7 h end-to-end workflow. Sensitivity and specificity for bacterial detection are 90% and 100%, respectively, and viral detection are 92% and 100% after 2 h of sequencing. Prospective validation on 33 consecutive lower respiratory tract samples from ventilated patients with suspected pneumonia shows 60% concordance with routine testing, detection of additional pathogens in 21% of samples and pathogen genomic assembly achieve for 42% of viruses and 33% of bacteria. Conclusions Although further workflow refinement and validation on samples containing a broader range of pathogens is required, it holds promise as a clinically deployable workflow suitable for evaluation in routine microbiology laboratories.

This study utilised lithogeochemistry and stable isotope geochemistry to assess the gold mineralisation in the host rocks of the Abansuoso area. It also studied the isotopic signature of hydrothermally altered and unaltered rocks as a tool for the preliminary prospecting of gold in Ghana’s Birimian belt. The research identified a close association between Au and As, Mo, and W, which is characteristic of orogenic gold deposits. The mineralised and unmineralised rocks show similar content of major and trace elements which suggests that the mineralisation did not significantly affect the primary composition of the mineralised rocks. The concentrations of δ18O (8.9‰ to 17.4‰, n = 22, mean = +13.7‰) and δD (−117 to −33‰, n = 22, mean = −57.9‰) in the rocks are comparable to those from other Birimian regions in Ghana and West Africa. The lack of variation in δ18O suggests a system buffered by rocks, with metamorphic fluid originating from rocks with identical δ18O values. However, the effect of mineralisation on the δD values of rocks is substantially more apparent than its effect on the δ18O values of the rocks.

With the continuous increase of rapid urbanization and population growth, sustainable urban land-use planning is becoming a more complex and challenging task for urban planners and decision-makers. Multi-objective land-use allocation can be regarded as a complex spatial optimization problem that aims to achieve the possible trade-offs among multiple and conflicting objectives. This paper proposes an improved Non-dominated Sorting Biogeography-Based Optimization (NSBBO) algorithm for solving the multi-objective land-use allocation problem, in which maximum accessibility, maximum compactness, and maximum spatial integration were formulated as spatial objectives; and space syntax analysis was used to analyze the potential movement patterns in the new urban planning area of the city of Kigali, Rwanda. Efficient Non-dominated Sorting (ENS) algorithm and crossover operator were integrated into classical NSBBO to improve the quality of non-dominated solutions, and local search ability, and to accelerate the convergence speed of the algorithm. The results showed that the proposed NSBBO exhibited good optimal solutions with a high hypervolume index compared to the classical NSBBO. Furthermore, the proposed algorithm could generate optimal land use scenarios according to the preferred objectives, thus having the potential to support the decision-making of urban planners and stockholders in revising and updating the existing detailed master plan of land use.

Smart ports, utilizing advanced and hybrid technologies, are gaining increasing attention for application in the maritime industry, with driver assistance and autonomous driving being pivotal in container-terminal operations. This study introduces a novel approach for enhancing object detection and distance estimation, focusing principally on decision support for reach stacker container handlers in port terminals by integrating generative and deep learning models. The EfficientDet model, enriched with integrated k-means clustering, is developed to detect and classify objects using a practical dataset of labeled images based on visual features. Moreover, generative models, specifically the diffusion model and generative adversarial network, are utilized to generate depth scenes for estimating object distances. Experimental results indicate that the proposed approach yields superior object detection and distance estimation outcomes in port terminal operations, characterized by high accuracy and reduced computational cost. The proposed method exhibits potential for application across various industries, including transportation, logistics, and security, where precise object detection and distance estimation are vital for efficient and secure operations.

Cobblestone lissencephaly (C-LIS) (TYPE II) is a rare and severe neuronal migration disorder characterized by a smooth brain surface with overmigrated neurons and abnormal formation of cerebral convolutions or gyri during fetal development, resulting in a cobblestone appearance. C-LIS is associated with eye anomalies and muscular dystrophy. This case report presents a detailed clinical and neuroimaging analysis of a patient diagnosed with cobblestone lissencephaly (Type II). It reviews pertinent literature to enhance our understanding of this complex condition. We report a case of a 6-year-old female child with cobblestone lissencephaly (C-LIS) (Type II) severe developmental delays, hypotonia, and recurrent intractable seizures. Magnetic resonance imaging (MRI) revealed a characteristic cobblestone appearance on the brain surface, indicative of abnormal neuronal migration. In addition to the classic findings of Type II Cobblestone lissencephaly, the patient displayed ventriculomegaly and cerebellar hypoplasia, contributing to the overall neurological impairment observed. The literature review highlights the genetic basis of cobblestone lissencephaly, emphasizing the involvement of genes associated with glycosylation processes and basement membrane integrity. Neuroimaging findings, including MRI and computed tomography scans, are crucial for accurate diagnosis and prognostication. Early identification of cobblestone lissencephaly allows for appropriate counseling and management strategies. However, the prognosis remains guarded, and interventions primarily focus on supportive care and seizure management. This case report contributes to the knowledge of cobblestone lissencephaly, shedding light on the clinical spectrum and neuroimaging features associated with this rare disorder. To clarify the underlying genetic mechanisms and possible therapeutic pathways for better patient outcomes, more investigation is necessary.

Background/purpose: Cognitive flexibility is a personality trait, which can influence how effectively a healthcare professional can manage a challenging clinical situation. This study explored the cognitive flexibility of undergraduate dental hygiene students at two universities in Asia to gather baseline information in order to consider whether there was an educational need for pre-clinical students with regards to this personality factor. Materials and methods: Participants were all undergraduate dental hygiene students in the 2022 academic year at Tokyo Medical and Dental University (TMDU; n = 79) and Taipei Medical University (TMU; n = 88). An anonymous questionnaire was distributed, which included questions on demographic information and the Cognitive Flexibility Inventory (CFI). Results: The response rates were 97.5% (TMDU) and 89.8% (TMU). The CFI total scores were 91.77 for TMDU and 95.87 for TMU, and there was no significant difference between the two schools. The Alternatives scores were significantly higher in TMU than TMDU (P = 0.044), but there were no significant differences in the Control scores between the two schools. There were also no significant differences between school years of both universities. Conclusion: The dental hygiene students from both dental schools exhibit moderate cognitive flexibility. The educators in both dental schools may consider whether they should investigate and develop this personality factor further during the undergraduate training of their dental hygiene students.

Background: /purposeIn cases where oral squamous cell carcinoma (OSCC) invades the jawbone, clinicians frequently observe abnormal attenuation on computed tomography (CT) and pathologic signal intensity (SI) on magnetic resonance (MR) imaging of the affected underlying bone marrow. This study introduced a concept of “underlying bone change” to examine its association with clinicopathological features and prognosis of OSCC, as well as its correlation with medullary invasion. Materials and methods: We enrolled 93 consecutive patients diagnosed with OSCC, who underwent mandibulectomy between 2010 and 2016. CT and MR images, along with electronic medical records, were reviewed to evaluate correlations between underlying bone changes, clinicopathological features, five-year overall survival, and medullary invasion. Results: Of the 93 patients, 69 (74.2%) exhibited underlying bone sclerosis on CT, and 74 (79.6%) displayed pathological SI on MR images. These underlying bone changes correlated with the T stage and recurrence, but not with overall survival.Medullary invasion, observed in 61 (65.6%) patients, was strongly associated with T and TNM stages and was linked to poorer overall survival.The underlying bone changes on CT and MR images were positively associated with medullary invasion; however, no significant differences were found in the occurrence of underlying bone changes between the subtypes based on the extent of medullary invasion. Conclusion: Underlying bone changes on CT and MR images can provide valuable insights into the aggressiveness of bone invasion by OSCC. Accurate interpretation of these imaging findings might be crucial for correctly delineating surgical margins and preventing the overestimation of tumor extent.

This review comprehensively examines the evolution and current state of interbody cage technology for lumbar interbody fusion (LIF). This review highlights the biomechanical and clinical implications of the transition from traditional static cage designs to advanced expandable variants for spinal surgery. The review begins by exploring the early developments in cage materials, highlighting the roles of titanium and polyetheretherketone in the advancement of LIF techniques. This review also discusses the strengths and limitations of these materials, leading to innovations in surface modifications and the introduction of novel materials, such as tantalum, as alternative materials. Advancements in three-dimensional printing and surface modification technologies form a significant part of this review, emphasizing the role of these technologies in enhancing the biomechanical compatibility and osseointegration of interbody cages. In addition, this review explores the increase in biodegradable and composite materials such as polylactic acid and polycaprolactone, addressing their potential to mitigate long-term implant-related complications. A critical evaluation of static and expandable cages is presented, including their respective clinical and radiological outcomes. While static cages have been a mainstay of LIF, expandable cages are noted for their adaptability to the patient’s anatomy, reducing complications such as cage subsidence. However, this review highlights the ongoing debate and the lack of conclusive evidence regarding the superiority of either cage type in terms of clinical outcomes. Finally, this review proposes future directions for cage technology, focusing on the integration of bioactive substances and multifunctional coatings and the development of patient-specific implants. These advancements aim to further enhance the efficacy, safety, and personalized approach of spinal fusion surgeries. Moreover, this review offers a nuanced understanding of the evolving landscape of cage technology in LIF and provides insights into current practices and future possibilities in spinal surgery.

Objectives Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Abstract Background Along the southern shoreline of Lake Malawi, the incidence of schistosomiasis is increasing with snails of the genera Bulinus and Biomphalaria transmitting urogenital and intestinal schistosomiasis, respectively. Since the underlying distribution of snails is partially known, often being focal, developing pragmatic spatial models that interpolate snail information across under-sampled regions is required to understand and assess current and future risk of schistosomiasis. Methods A secondary geospatial analysis of recently collected malacological and environmental survey data was undertaken. Using a Bayesian Poisson latent Gaussian process model, abundance data were fitted for Bulinus and Biomphalaria. Interpolating the abundance of snails along the shoreline (given their relative distance along the shoreline) was achieved by smoothing, using extracted environmental rainfall, land surface temperature (LST), evapotranspiration, normalised difference vegetation index (NDVI) and soil type covariate data for all predicted locations. Our adopted model used a combination of two-dimensional (2D) and one dimensional (1D) mapping. Results A significant association between normalised difference vegetation index (NDVI) and abundance of Bulinus spp. was detected (log risk ratio − 0.83, 95% CrI − 1.57, − 0.09). A qualitatively similar association was found between NDVI and Biomphalaria sp. but was not statistically significant (log risk ratio − 1.42, 95% CrI − 3.09, 0.10). Analyses of all other environmental data were considered non-significant. Conclusions The spatial range in which interpolation of snail distributions is possible appears < 10km owing to fine-scale biotic and abiotic heterogeneities. The forthcoming challenge is to refine geospatial sampling frameworks with future opportunities to map schistosomiasis within actual or predicted snail distributions. In so doing, this would better reveal local environmental transmission possibilities. Graphical Abstract

Abstract Stroke is one of the major causes of death worldwide, and is closely associated with atherosclerosis of the carotid artery. Panoramic radiographs (PRs) are routinely used in dental practice, and can be used to visualize carotid artery calcification (CAC). The purpose of this study was to automatically and robustly classify and segment CACs with large variations in size, shape, and location, and those overlapping with anatomical structures based on deep learning analysis of PRs. We developed a cascaded deep learning network (CACSNet) consisting of classification and segmentation networks for CACs on PRs. This network was trained on ground truth data accurately determined with reference to CT images using the Tversky loss function with optimized weights by balancing between precision and recall. CACSNet with EfficientNet-B4 achieved an AUC of 0.996, accuracy of 0.985, sensitivity of 0.980, and specificity of 0.988 in classification for normal or abnormal PRs. Segmentation performances for CAC lesions were 0.595 for the Jaccard index, 0.722 for the Dice similarity coefficient, 0.749 for precision, and 0.756 for recall. Our network demonstrated superior classification performance to previous methods based on PRs, and had comparable segmentation performance to studies based on other imaging modalities. Therefore, CACSNet can be used for robust classification and segmentation of CAC lesions that are morphologically variable and overlap with surrounding structures over the entire posterior inferior region of the mandibular angle on PRs.

Abstract Background The onset of the COVID-19 pandemic catalysed a monumental shift in the field of continuing professional development (CPD). Prior to this, the majority of CPD group-learning activities were offered in-person. However, the pandemic forced the field to quickly pivot towards more novel methods of learning and teaching in view of social distancing regulations. The purpose of this study was to obtain the perspectives of CPD leaders on the impact of the pandemic to elucidate trends, innovations, and potential future directions in the field. Methods Semi-structured interviews were conducted between April-September 2022 with 23 CPD leaders from Canada and the USA. Interviews were audio-recorded, transcribed, and de-identified. A thematic analysis approach was used to analyse the data and generate themes. Results Participants characterised COVID-19 as compelling widespread change in the field of CPD. From the interviews, researchers generated six themes pertaining to the impact of the pandemic on CPD: (1) necessity is the mother of innovation, (2) the paradox of flexibility and accessibility, (3) we’re not going to unring the bell, (4) reimagining design and delivery, (5) creating an evaluative culture, and (6) a lifeline in times of turmoil. Conclusion This qualitative study discusses the impact of the pandemic on the field of CPD and leaders’ vision for the future. Despite innumerable challenges, the pandemic created opportunities to reform design and delivery. Our findings indicate a necessity to maintain an innovative culture to best support learners, to improve the healthcare system, and to prepare for future emergencies.

Impaired respiratory function secondary to acute or chronic respiratory disease poses a significant clinical and healthcare burden. Intrapulmonary percussive ventilation (IPV) is used in various clinical settings to treat excessive airway secretions, pulmonary atelectasis, and impaired gas exchange. Despite IPV’s wide use, there is a lack of clinical guidance on IPV application which may lead to inconsistency in clinical practice. This scoping review aimed to summarise the clinical application methods and dosage of IPV used by clinicians and researchers to provide guidance. A two-staged systematic search was conducted to retrieve studies that used IPV in inpatient and outpatient settings. MEDLINE, EMBASE, CINAHL, Scopus, and Google scholar were searched from January 1979 till 2022. Studies with patients aged ≥16 years and published in any language were included. Two reviewers independently screened the title and abstract, reviewed full text articles, and extracted data. Search yielded 514 studies. After removing duplicates and irrelevant studies, 25 studies with 905 participants met the inclusion criteria. This is the first scoping review to summarise IPV application methods and dosages from the available studies in intensive care unit (ICU), acute inpatient (non-ICU), and outpatient settings. Some variations in clinical applications and prescribed dosages of IPV were noted. Despite variations, common trends in clinical application and prescription of IPV dosages were observed and summarised to assist clinicians with IPV intervention. Although an evidence-based clinical guideline could not be provided, this review provides detailed information on IPV application and dosages in order to provide clinical guidance and lays a foundation towards developing a clinical practice guideline in the future.

Objective(s): Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins.Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed.Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group.Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

Abstract Thermal radiation is intrinsically broadband, incoherent and non-directional. The ability to beam thermal energy preferentially in one direction is not only of fundamental importance, but it will enable high radiative efficiency critical for many thermal sensing, imaging, and energy devices. Over the years, different photonic materials and structures have been designed utilizing resonant and propagating modes to generate directional thermal emission. However, such thermal emission is narrowband and polarised, leading to limited thermal transfer efficiency. Here we experimentally demonstrate ultrabroadband polarisation-independent directional control of thermal radiation with a pixelated directional micro-emitter. Our compact pixelated directional micro-emitter facilitates tunable angular control of thermal radiation through non-imaging optical principles, producing a large emissivity contrast at different view angles. Using this platform, we further create a pixelated infrared display, where information is only observable at certain directions. Our pixelated non-imaging micro-optics approach can enable efficient radiative cooling, infrared spectroscopy, thermophotovoltaics, and thermal camouflaging.

Abstract Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.