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Due to the adverse ecological impacts of prolonged and excessive use of agrochemicals, many researchers have called for the adoption of eco-friendly materials in farming. Consequently, the aim of this study is to profile the biocontrol agents, nitrogen-fixing, and indole-acetic-acid-producing bacteria present in anthill soil. Anthill soils and adjacent soils were collected, and their physicochemical properties were analysed using standard analytical methods. Viable bacteria were isolated and screened for plant growth-promoting (PGP) activity using standard biochemical, morphological, and bacteriological methods. The PGP capacity of the isolates was evaluated using standard protocol for nitrogen fixation and indole-acetic-acid production, while antagonistic effect against plant pathogens was evaluated using the disk diffusion assay. Results revealed that Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus sp. isolated from the anthill soil demonstrated PGP characteristics including IAA production and nitrogen fixation. Bacillus sp. exhibited zones of clearance with values of 20.00 ± 1.50 mm, 20.00 ± 1.75 mm, 17.00 ± 1.33 mm, and 17.00 ± 1.33 mm against Aspergillus niger, Trichoderma sp., Penicillium sp., and Fusarium sp., respectively. This study demonstrated that anthill soils contain beneficial microbes with the potential to stimulate plant growth and suppress soil-borne plant pathogens

Abstract Background Reliable ECGs are crucial for diagnosing arrhythmias, yet a lack of standardization impedes arrhythmia diagnosis and treatment in horses. Objectives To objectively determine an optimal position of Einthoven's triangle for ECG recordings in horses at rest, which can form the basis for standardized ECG recording and improve diagnosis and treatment of arrhythmias. Animals The study involved 72 healthy, warmblood horses aged between 3 and 20 years. Methods In view of future 12‐lead studies and vectorcardiography, requiring an orthogonal system, Einthoven's triangle was positioned around the heart, in the transverse plane. Therefore, 11 electrodes were placed encircling the thorax behind the olecranon, to construct triangles with a horizontal base. Electrocardiogram recordings from different triangles were analyzed. Signal processing involved filtering, R peak detection, and median complex generation. Principal component analysis (PCA) and Euclidean distance measures were employed for data analysis. Results The left mid‐thoracic and ventral regions had high PCA scores, indicating high information content. Base‐down triangles exhibited higher summed Euclidean distances, contributing to enhanced diagnostic capabilities. A base‐down triangle, called “Delta (Δ) configuration” emerged as most informative, while meeting all criteria. Conclusions and Clinical Importance The base‐down “Delta configuration” is the optimal Einthoven's triangle adapted for horses, providing large amplitudes and potential to provide basic insights into the mechanisms and origins of cardiac arrhythmias. Because the Delta configuration is positioned in the transverse plane, it forms the ideal basis for 12‐lead ECG recordings that provide vectorcardiograms in an orthogonal coordinate system. Standardizing electrode positioning could improve ECG data comparability in equine cardiology.

Abstract Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aβ levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aβ-binding monocytes may play a role in CNS Aβ clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

Abstract Background Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences. Therefore, we specifically investigated sex-specific effects on the interaction between emotionally induced changes in physiology and behavioral performance on a decision-making task. Methods Skin conductance responses of twenty-nine adults with ADHD (n = 16 male; n = 13 female) and thirty-three adults in the control group (n = 14 male; n = 19 female) were recorded during the performance in a modified version of the Balloon Analogue Risk Task (BART). Additional questionnaires were used to reveal insights in the self-assessment of emotional competence, risk perception, and feedback sensitivity. Emotional arousal and decision-making behavior were analyzed using linear mixed-effects models. Results Results showed different effects of sex on risk behaviors in controls and ADHD. In contrast to healthy controls, female adults with ADHD showed a significantly greater risk engagement in the BART compared to males with ADHD. This contrary sex relation was not observed in skin conductance responses and revealed a significantly different sex-dependent correlation of body response and behavioral task performance in ADHD. Comparisons with results from self-assessments furthermore indicate a reduced behavioral self-perception in women with ADHD, but not in men. Conclusion In summary, we found an altered interaction between physiological activity and risky behavior in women with ADHD. Thus, the present study indicates a reduced sensitivity towards the own bodily responses in women with ADHD, which could consequently cause increased risky DM behavior in daily life. The current results suggest that more consideration needs to be given to sex-specific effects on physiological processes and behavior in adults with ADHD.

Abstract Background Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths. Methods We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states. Results We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1–5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles. Conclusions Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10–30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged.

Abstract Robust object detection is crucial for automating underwater marine debris collection. While supervised deep learning achieves state-of-the-art performance in discriminative tasks, replicating this success on underwater data is challenging. The generalization of these methods suffers due to a lack of available annotated data considering different sources of variation in the unstructured underwater environment and imaging conditions. In this paper, we present the Seaclear Marine Debris Dataset, the first publicly available shallow-water marine debris dataset annotated for instance segmentation/object detection. The dataset contains 8610 images collected using ROVs at multiple locations and with different cameras, annotated for 40 object categories, encompassing not only litter but also observed animals, plants, and robot parts. As part of the technical validation, we provide baseline results for object detection using Faster RCNN and YOLOv6 models. Furthermore, we demonstrate the non-triviality of generalizing the trained model performance to unseen sites and cameras due to domain shift. This underscores the value of the presented dataset in further developing robust models for underwater debris detection.

This study aimed to investigate the physiological, perceptual, and biomechanical differences between male and female soldiers across several military-relevant load and walking speed combinations. Eleven female and twelve male soldiers completed twelve 12 min walking trials at varying speeds (3.5 km·h−1, 5.5 km·h−1, 6.5 km·h−1) and with varying external loads (7.2 kg, 23.2 kg, 35.2 kg). Physiological (indirect calorimetry, heart rate), perceptual (perceived exertion), and biomechanical (spatiotemporal, kinematic, kinetic) outcomes were measured throughout each trial. Females had a lower aerobic capacity and lower body strength than males, which resulted in them working at a greater exercise intensity (%VO2peak and heart rate) but with a lower oxygen pulse. Females demonstrated higher breathing frequency and perceived exertion with specific loads. At selected loads and speeds, frontal and sagittal pelvis, hip, and knee motions and forces were greater for females. Females consistently displayed greater relative stride length and step width. In conclusion, this study demonstrates the importance of tailored interventions, periodisation, and nutritional strategies for female military personnel, given their higher relative work rate and increased injury risk during load carriage tasks. Understanding these differences is crucial for preparing female soldiers for the physical demands of military service.

Abstract Electrocorticography is an established neural interfacing technique wherein an array of electrodes enables large-area recording from the cortical surface. Electrocorticography is commonly used for seizure mapping however the implantation of large-area electrocorticography arrays is a highly invasive procedure, requiring a craniotomy larger than the implant area to place the device. In this work, flexible thin-film electrode arrays are combined with concepts from soft robotics, to realize a large-area electrocorticography device that can change shape via integrated fluidic actuators. We show that the 32-electrode device can be packaged using origami-inspired folding into a compressed state and implanted through a small burr-hole craniotomy, then expanded on the surface of the brain for large-area cortical coverage. The implantation, expansion, and recording functionality of the device is confirmed in-vitro and in porcine in-vivo models. The integration of shape actuation into neural implants provides a clinically viable pathway to realize large-area neural interfaces via minimally invasive surgical techniques.

IntroductionPencil pine (Athrotaxis cupressoides) is an iconic, paleoendemic tree restricted to historic fire refugia in Tasmania’s western mountains. Anthropogenic climate change is increasingly exposing these areas to wildfire. Given that pencil pines have little capacity to recover from fire, and show scarce natural recruitment across their core range, they will be lost from many areas without interventions to restore population viability to burnt stands.MethodsWe conducted a large-scale field study targeting pencil pine stands burnt in recent (2016) and historic (1960) fires. Using small (0.5 m2) experimental plots distributed across a range of topography and vegetation, we trialled three interventions: i) protecting groups of naturally germinated seedlings from herbivores in situ (35 plots); ii) introducing seeds via multiple sowing methods (300 plots); and iii) transplanting tube stock propagated from seed or cutting material, with and without herbivore protection (1007 plots).ResultsWe found that protecting natural germinants from herbivores did not prevent seedling mortality over 2.5 years, and sowing interventions largely failed. Most transplants exposed to herbivores failed to establish after 1.5 years, but establishment rates were high with herbivore exclusion, indicating strong predation by native macropod herbivores. Transplant establishment also varied with fine-scale topography, with the best outcomes in well-drained and Sphagnum dominated positions, and the worst outcomes in poorly-drained positions, suggesting young pencil pines are sensitive to waterlogging. Transplant establishment rates varied little between recently and historically burnt sites, and were insensitive to how plants were propagated.DiscussionIn summary, transplanting tube stock with herbivore protection is a promising method for restoring burnt pencil pine stands, and establishment rates can be improved by selecting favourable planting positions at fine scales. Our findings suggest pencil pine stands burnt decades previously are suitable for restoration. Managers seeking to conserve pencil pines may begin restoring both historically and recently burnt stands, alongside protecting unburned stands from fire. Interventions should be refined through adaptive management, including re-surveys of this long-term trial.

The genus Amblyomma contains the highest percentage of reptile-associated ticks, and comprises approximately nine subgenera. One of these subgenera is Adenopleura, which also encompasses Amblyomma javanense, and its type species Amblyomma compressum. This study describes a new Amblyomma species associated with Bengal monitor lizards (Varanus bengalensis) based on morphology and its mitogenome in Khyber Pakhtunkhwa, Pakistan. Reptiles belonging to different genera were examined for Amblyomma ticks and only the monitor lizard was infested with ticks in the District Bajaur. Collected Amblyomma cf. javanense ticks were analyzed and formally described as a new species. Overall, 57 A. cf. javanense ticks were collected on monitor lizards (4/27) with a 15% prevalence of infestation, 2.1 mean abundance, and 14.3 mean intensity. Ticks comprised males (n = 23, 40%), females (n = 14, 25%) and nymphs (n = 20, 35%), while no larvae were found. BLAST analysis of A. cf. javanense sequences showed the following maximum identities; 98.25% with undetermined Amblyomma species based on 12S rRNA, 96.07% with A. javanense based on 16S rRNA, 99.56% and 90.95% with an Amblyomma sp. and A. javanense, respectively, based on ITS2. Moreover, the mitochondrial genome of A. cf. javanense showed maximum identities of 80.75%, 80.48% and 79.42% with Amblyomma testudinarium, A. javanense, and Amblyomma sp., respectively. The phylogenetic analysis of A. cf. javanense revealed that its 12S rRNA and 16S rRNA are closely related to an Amblyomma sp. and A. javanense, respectively, from Sri Lanka, its ITS2 is closely related to A. javanense from China and an Amblyomma sp. from Sri Lanka, and its mitogenome is closely related to A. javanense and Amblyomma sp. from China. The pairwise distance analysis resulted in divergence of 0–1.71% (12S rRNA), 0–17.5% (16S rRNA), 0–9.1% (ITS2) and 0–20.5% (mitochondrial genome). We also contributed the full-length mitochondrial genome sequence of A. compressum and showed that this species does not share a most recent common ancestor with A. javanense. As the subgenus Adenopleura is paraphyletic, this study could help to understand the systematics and phylogeny of this taxon.

Summary: Background: There have been no detailed descriptions of infants born to mothers treated for drug resistant TB in pregnancy. Critical case history assessment is important to identify risks and guide clinical practice. Methods: In a cohort of pregnant women with multidrug or rifampicin resistant (MDR/RR)-TB enrolled between 1 January 2013 and 31 December 2022, we followed mother-infant pairs until the infant was 12 months old. We performed critical case history assessments to explore potential mechanisms of Mycobacterium tuberculosis transmission to the infant, and to describe the clinical presentation and disease trajectories observed in infants diagnosed with TB. Findings: Among 101 mother-infant pairs, 23 (23%) included infants diagnosed with TB disease; 16 were clinically diagnosed and seven had microbiological confirmation (five MDR/RR-TB, two drug-susceptible TB). A positive maternal sputum culture at the time of delivery was significantly associated with infant TB risk (p = 0.023). Of the 12 infants diagnosed with TB in the first three months of life, seven (58%) of the mothers were culture positive at delivery; of whom four reported poor TB treatment adherence. However, health system failures, including failing to diagnose and treat maternal MDR/RR-TB, inadequate screening of newborns at birth, not providing appropriate TB preventive therapy (TPT), and M. tuberculosis transmission from non-maternal sources also contributed to TB development in infants. Interpretation: Infants born to mothers with MDR/RR-TB are at greatest risk if maternal adherence to MDR/RR-TB treatment or antiretroviral therapy (ART) is sub-optimal. In a high TB incidence setting, infants are also at risk of non-maternal household and community transmission. Ensuring maternal TB diagnosis and appropriate treatment, together with adequate TB screening and prevention in all babies born to mothers or households with TB will minimise the risk of infant TB disease development. Funding: South African Medical Research Council.

Abstract Non-small cell lung carcinoma (NSCLC) exhibits a heightened propensity for brain metastasis, posing a significant clinical challenge. Mucin 5ac (MUC5AC) plays a pivotal role in the development of lung adenocarcinoma (LUAD); however, its role in causing brain metastases remains unknown. In this study, we aimed to investigate the contribution of MUC5AC to brain metastasis in patients with LUAD utilizing various brain metastasis models. Our findings revealed a substantial increase in the MUC5AC level in LUAD brain metastases (LUAD-BrM) samples and brain-tropic cell lines compared to primary samples or parental control cell lines. Intriguingly, depletion of MUC5AC in brain-tropic cells led to significant reductions in intracranial metastasis and tumor growth, and improved survival following intracardiac injection, in contrast to the observations in the control groups. Proteomic analysis revealed that mechanistically, MUC5AC depletion resulted in decreased expression of metastasis-associated molecules. There were increases in epithelial-to-mesenchymal transition, tumor invasiveness, and metastasis phenotypes in tumors with high MUC5AC expression. Furthermore, immunoprecipitation and proteomic analysis revealed a novel interaction of MUC5AC with Annexin A2 (ANXA2), which activated downstream matrix metalloproteases and facilitated extracellular matrix degradation to promote metastasis. Disrupting MUC5AC-ANXA2 signaling with a peptide inhibitor effectively abrogated the metastatic process. Additionally, treatment of tumor cells with an astrocyte-conditioned medium or the chemokine CCL2 resulted in upregulation of MUC5AC expression and enhanced brain colonization. In summary, our study demonstrates that the MUC5AC/ANXA2 signaling axis promotes brain metastasis, suggesting a potential therapeutic paradigm for LUAD patients with high MUC5AC expression.

Abstract Objective Many patients with melanoma treated with immune checkpoint inhibitors (ICIs) do not derive response. Preclinical and retrospective studies identified that inhibition of the cyclooxygenase (COX) pathway may improve response to ICI treatment. Methods This prospective single site phase II trial accrued patients with advanced/metastatic melanoma. Participants underwent high-dose aspirin daily combined with pembrolizumab and ipilimumab every 3 weeks for 4 cycles followed by high-dose aspirin and pembrolizumab monotherapy. The primary endpoint was objective response rate (ORR). Longitudinal sampling of blood was performed to assess peripheral immune correlates. Results Twenty-seven subjects were enrolled with median follow-up of 32 months. An ORR of 62.9% was reached prior to discontinuation due to low likelihood of achieving the pre-specified ORR of 80%. 17 patients (63%) experienced a treatment-related adverse event (TRAEs) grade 3 or higher. A per-protocol analysis showed that patients able to continue aspirin alongside ICI through the induction period experienced significant survival benefit. Ten cytokines and increased regulatory T cells in the periphery correlated with beneficial response. Conclusions The addition of high-dose aspirin to combination ICI within this study results in response comparable to ICI alone. Future clinical studies of COX inhibition will need to focus on mitigation of AEs to establish the clinical utility of this combination.

Abstract Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming “Candidatus Methanoperedens” archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding nanowire-like electron-transferring cytochromes and cell surface proteins are more highly expressed than those of host Methanoperedens, indicating that Borgs augment the Methanoperedens activity in situ. We reconstructed the first complete 4.00 Mbp genome for a Methanoperedens that is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enable Methanoperedens to distinguish their genomes from those of Borgs. Very high Borg to Methanoperedens ratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.

Objectives: Climate change is expected to have major impacts on plant species distribution worldwide. These changes can affect plant species in three ways: the timing of seasonal activities (phenology), physiology and distribution. This study aims to predict the effect of shifting climatic conditions on the major vegetation units along an aridity gradient through Namibia. Study area: Namibia’s vegetation is characterised by open woodland in the northeast to low open shrubland in the southern part of the country. These differences are a result of increasing aridity from north to south with a rainfall gradient from 100 mm to 600 mm. Namibia is projected to have an increase in annual mean temperature of 2°C by the end of the 21st century. Methods: A vegetation classification was done for 1,986 relevés using cluster analysis, a Multi-Response Permutation Procedure and indicator species analysis. The current distribution of the vegetation classes was modelled with Random Forest. Future projections for the most important climate variables were used to model the potential distribution of the vegetation units in 2080. This modelling approach used two scenarios of Representative Concentration Pathways (4.5 and 8.5) from two Global Climate Models – the IPSL–CM5A–LR and HAdGEM2–ES. Results: The predicted distribution shows a high expansion potential of Eragrostis rigidior-Peltophorum africanum mesic thornbush savannas, Combretum africanum-Terminalia sericea broad-leafed savannas and Senegalia mellifera-Dichrostachys cinerea degraded thornbush savannas towards the south under both scenarios. Conclusions: The model indicated the ability to classify and predict vegetation units to future climatic conditions. Half of the vegetation units are expected to undergo significant contraction. Overall, RCP8.5 conditions favour the proliferation of certain vegetation types, particularly Combretum collinum-Terminalia sericea broad-leafed savannas and Senegalia mellifera-Dichrostachys cinerea degraded thornbush savannas, potentially displacing other vegetation types. Taxonomic reference: Klaassen and Kwembeya (2013) for vascular plants, except Kyalangalilwa et al. (2013) for the genera Senegalia and Vachellia s.l. (Fabaceae). Abbreviations: CDM = Community Distribution Model; CMIP5 = Coupled Model Inter-comparison Project Phase 5; EVI = Enhanced Vegetation Index; GCM = General Circulation Model; IV = Indicator Value; ISA = Indicator Species Analysis; MAP = mean annual precipitation; MAT = mean annual temperature; MRPP = Multi-Response Permutation Procedure; NMS = Non-Metric Multidimensional Scaling; RF = Random Forest; RCPs = Representative Concentration Pathways; SDM = species distribution model.

Abstract Most genetic variants associated with fertility in mammals fall in non-coding regions of the genome and it is unclear how these variants affect fertility. Here we use genome-wide association summary statistics for Heifer puberty (pubertal or not at 600 days) from 27,707 Bos indicus, Bos taurus and crossbred cattle; multi-trait GWAS signals from 2119 indicine cattle for four fertility traits, including days to calving, age at first calving, pregnancy status, and foetus age in weeks (assessed by rectal palpation of the foetus); and expression quantitative trait locus for whole blood from 489 indicine cattle, to identify 87 putatively functional genes affecting cattle fertility. Our analysis reveals a significant overlap between the set of cattle and previously reported human fertility-related genes, impling the existence of a shared pool of genes that regulate fertility in mammals. These findings are crucial for developing approaches to improve fertility in cattle and potentially other mammals.

Ixodid ticks are obligate blood-feeding arthropods and important vectors of pathogens. In Mallorca, almost no data on the tick fauna are available. Herein, we investigated ticks and tick-borne pathogens in ticks collected from dogs, a cat and humans in Mallorca as result of a citizen science project. A total of 91 ticks were received from German tourists and residents in Mallorca. Ticks were collected from March to October 2023 from dogs, cat and humans, morphologically and genetically identified and tested for pathogens by PCRs. Six tick species could be identified: Ixodes ricinus (n = 2), Ixodes ventalloi (n = 1), Hyalomma lusitanicum (n = 7), Hyalomma marginatum (n = 1), Rhipicephalus sanguineus s.l. (n = 71) and Rhipicephalus pusillus (n = 9). Rhipicephalus sanguineus s.l. adults were collected from dogs and four females from a cat and the 16S rDNA sequences identified it as Rh. sanguineus s.s. Hyalomma lusitanicum was collected from 1 human, 1 dog and 5 specimens were collected from the ground in the community of Santanyi, together with one H. marginatum male. This is the first report of Hyalomma marginatum in Mallorca. Both I. ricinus were collected from humans and I. ventalloi female was collected from a dog. All ticks tested negative for Anaplasma phagocytophilum, Coxiella spp., Francisella spp., and piroplasms. In 32/71 (45%) specimens of Rh. sanguineus s.s., Rickettsia spp. could be detected and in 18/32 (56.2%) sequenced tick DNAs R. massiliae was identified. Ixodes ventalloi female and both I. ricinus tested positive in the screening PCR, but the sequencing for the identification of the Rickettsia sp. failed.

Abstract The causes of temporal fluctuations in adult traits are poorly understood. Here, we investigate the genetic determinants of within-person trait variability of 8 repeatedly measured anthropometric traits in 50,117 individuals from the UK Biobank. We found that within-person (non-directional) variability had a SNP-based heritability of 2–5% for height, sitting height, body mass index (BMI) and weight (P $$\le$$ ≤ 2.4 × 10− 3). We also analysed longitudinal trait change and show a loss of both average height and weight beyond about 70 years of age. A variant tracking the Alzheimer’s risk APOE- $${{{{{\mathcal{E}}}}}}4$$ E 4 allele (rs429358) was significantly associated with weight loss ( $$\beta$$ β = −0.047 kg per yr, s.e. 0.007, P = 2.2 × 10−11), and using 2-sample Mendelian Randomisation we detected a relationship consistent with causality between decreased lumbar spine bone mineral density and height loss (b xy = 0.011, s.e. 0.003, P = 3.5 × 10−4). Finally, population-level variance quantitative trait loci (vQTL) were consistent with within-person variability for several traits, indicating an overlap between trait variability assessed at the population or individual level. Our findings help elucidate the genetic influence on trait-change within an individual and highlight disease risks associated with these changes.

Abstract Electron-electron interactions in materials lead to exotic many-body quantum phenomena, including Mott metal-insulator transitions (MITs), magnetism, quantum spin liquids, and superconductivity. These phases depend on electronic band occupation and can be controlled via the chemical potential. Flat bands in two-dimensional (2D) and layered materials with a kagome lattice enhance electronic correlations. Although theoretically predicted, correlated-electron Mott insulating phases in monolayer 2D metal-organic frameworks (MOFs) with a kagome structure have not yet been realised experimentally. Here, we synthesise a 2D kagome MOF on a 2D insulator. Scanning tunnelling microscopy (STM) and spectroscopy reveal a MOF electronic energy gap of ∼200 meV, consistent with dynamical mean-field theory predictions of a Mott insulator. Combining template-induced (via work function variations of the substrate) and STM probe-induced gating, we locally tune the electron population of the MOF kagome bands and induce Mott MITs. These findings enable technologies based on electrostatic control of many-body quantum phases in 2D MOFs.

Purpose: In postoperative breast irradiation, changes in the breast contour and arm positioning can result in patient positioning errors and offline replanning. This can lead to increased treatment burden and strain on departmental logistics because of the need for additional cone beam computed tomography (CBCT) images or even a new radiation therapy treatment plan (TP). Online daily adaptive radiation therapy (oART) could provide a solution to these challenges. We have clinically implemented and evaluated the feasibility of oART for whole breast irradiation. Methods and Materials: Twenty patients treated with postoperative whole breast right irradiation (5 × 5.2 Gy) were included in BREAST-ART, a prospective single-arm trial. The dosimetry of the reference TP calculated on the daily anatomy and adaptive TP were compared. Duration of the oART workflow, in-house satisfaction questionnaires, and acute toxicity (National Cancer Institute Common Terminology Criteria for Adverse Event v5.0) were collected. The oART workflow was evaluated by investigating the impact of manual corrections of influencer and target contours on treatment time and quality. Results: In the first 17 patients (85 fractions), the on-couch time, ie, the time between the end of CBCT1 and CBCT3, was a median of 13.8 minutes (range, 11–25). Retrospective evaluation of the use of the influencer (ie, breast) in 4 patients (20 fractions) and manual correction of the most cranial and caudal target contours (ie, 4 mm) in 10 patients (36 fractions) was done. This resulted in a reduced on-couch time in the last 3 clinical patients to a median of 13.0 minutes (range, 11–19). No grade 3 or higher toxicity was observed, and 19 of 20 patients indicated that they preferred the same treatment again. Skin marks for patient positioning during treatment were no longer necessary. Conclusions: This study showed the feasibility, challenges, and practical solutions for the implementation of oART for breast cancer patients. Future work will focus on more complex breast indications, such as whole breast, including axillary nodes, to further investigate the benefits and challenges of oART in breast cancer.

Background Gambling disorder (GD) has become a wide concern in Indonesia, as many negative consequences arise from this psychiatric condition. Prompt treatment with an appropriate method of delivery is required to achieve optimal outcomes in GD patients. This protocol paper outlines a study to determine the effectiveness, acceptability, and feasibility of internet-based cognitive behavioral therapy (iCBT) in treating GD in Indonesia. Methods This non-randomized pilot and feasibility study will recruit 20 people with GD. All participants will receive the iCBT intervention through self-learning videos and guided weekly group sessions. The effectiveness of the intervention will be assessed at baseline (week 0), post- treatment completion (week 10), and 6 weeks post-treatment (week 16). The outcomes measured will be the change in gambling symptoms, gambling urges, cognitive distortions, readiness to change, emotional problems, and quality of life of the participants. Discussion The feasibility of iCBT for GD patients in Indonesia will be assessed by this study. The study’s results will give an indication of the acceptability of the intervention and the feasibility of a subsequent conclusive trial. The delivery of iCBT may help to address the issue of treatment access in an extensive geographical region and provide immediate implications as a treatment resource for GD in practice.

IntroductionBovine Genital Campylobacteriosis (BGC), caused by Campylobacter fetus subsp. venerealis, is a sexually transmitted bacterium that significantly impacts cattle reproductive performance. However, current detection methods lack consistency and reliability due to the close genetic similarity between C. fetus subsp. venerealis and C. fetus subsp. fetus. Therefore, this study aimed to utilize complete genome analysis to distinguish genetic features between C. fetus subsp. venerealis and other subspecies, thereby enhancing BGC detection for routine screening and epidemiological studies.Methods and resultsThis study reported the complete genomes of four C. fetus subsp. fetus and five C. fetus subsp. venerealis, sequenced using long-read sequencing technologies. Comparative whole-genome analyses (n = 25) were conducted, incorporating an additional 16 complete C. fetus genomes from the NCBI database, to investigate the genomic differences between these two closely related C. fetus subspecies. Pan-genomic analyses revealed a core genome consisting of 1,561 genes and an accessory pangenome of 1,064 genes between the two C. fetus subspecies. However, no unique predicted genes were identified in either subspecies. Nonetheless, whole-genome single nucleotide polymorphisms (SNPs) analysis identified 289 SNPs unique to one or the C. fetus subspecies. After the removal of SNPs located on putative genomic islands, recombination sites, and those causing synonymous amino acid changes, the remaining 184 SNPs were functionally annotated. Candidate SNPs that were annotated with the KEGG “Peptidoglycan Biosynthesis” pathway were recruited for further analysis due to their potential association with the glycine intolerance characteristic of C. fetus subsp. venerealis and its biovar variant. Verification with 58 annotated C. fetus genomes, both complete and incomplete, from RefSeq, successfully classified these seven SNPs into two groups, aligning with their phenotypic identification as CFF (Campylobacter fetus subsp. fetus) or CFV/CFVi (Campylobacter fetus subsp. venerealis and its biovar variant). Furthermore, we demonstrated the application of mraY SNPs for detecting C. fetus subspecies using a quantitative PCR assay.DiscussionOur results highlighted the high genetic stability of C. fetus subspecies. Nevertheless, Campylobacter fetus subsp. venerealis and its biovar variants encoded common SNPs in genes related to glycine intolerance, which differentiates them from C. fetus subsp. fetus. This discovery highlights the potential of employing a multiple-SNP assay for the precise differentiation of C. fetus subspecies.

IntroductionChanges to bone physiology play a central role in the development of osteoarthritis with the mechanosensing osteocyte releasing factors that drive disease progression. This study developed a humanised in vitro model to detect osteocyte responses to either interleukin-6, a driver of degeneration and bone remodelling in animal and human joint injury, or mechanical loading, to mimic osteoarthritis stimuli in joints.MethodsHuman MSC cells (Y201) were differentiated in 3-dimensional type I collagen gels in osteogenic media and osteocyte phenotype assessed by RTqPCR and immunostaining. Gels were subjected to a single pathophysiological load or stimulated with interleukin-6 with unloaded or unstimulated cells as controls. RNA was extracted 1-hour post-load and assessed by RNAseq. Markers of pain, bone remodelling, and inflammation were quantified by RT-qPCR and ELISA.ResultsY201 cells embedded within 3D collagen gels assumed dendritic morphology and expressed mature osteocytes markers. Mechanical loading of the osteocyte model regulated 7564 genes (Padj p90% of the genes in the osteocyte transcriptome signature. Mechanical loading and inflammatory stimulation regulated genes and proteins implicated in osteoarthritis symptoms of pain as well as inflammation and degeneration underlying disease progression. Nearly half of the genes classified as ‘effectors’ in GWAS were mechanically regulated in this model. This model will be useful in identifying new mechanisms underlying bone and joint pathologies and testing drugs targeting those mechanisms.

Porphyry-type Cu ± Au ± Mo deposits form in the upper (ca. 2–5 km deep) parts of large, long-lived magmatic-hydrothermal systems in which mineralising fluids are thought to be derived from mid-to shallow-crustal magma chambers. Increasingly, however, magmatic systems are viewed as consisting of mush with minor and transient lenses of magma, with mush being a variably packed framework of crystals with interstitial melt and magmatic volatile phase (MVP). In this context, questions remain as to the source (mainly depth) and mechanisms of transport and focussing of the vast volumes of fluids required for shallow level porphyry-type mineralisation. Even more problematic is a paucity of first-order textural evidence for the presence of mush in magmatic-hydrothermal systems, including those which host porphyry-type deposits. To address this, we have studied the aplitic porphyry cupola of the Saginaw Hill magmatic system, Tuscon, Arizona, United States, where magmatic-hydrothermal features are exceptionally well exposed, including a massive silica cap, quartz unidirectional solidification textures (USTs), stockworks of multiple generations of variably mineralised quartz veins and mineralised miarolitic cavities. From field-to micro-scale textural and geochemical studies, particularly observations of vermiform quartz between earlier generations of magmatic quartz and feldspar, we evidence the development of fluid pathways through mush at the magmatic-hydrothermal transition. These are shown to connect and provide fluids and ore constituents to the mineralised miarolitic cavities and early quartz vein stockworks. We suggest that this process should be considered in all new genetic, exploration and numerical models for porphyry and similar types of magmatic-hydrothermal ore-deposits.

Abstract Background Amblyomma is the third most diversified genus of Ixodidae that is distributed across the Indomalayan, Afrotropical, Australasian (IAA), Nearctic and Neotropical biogeographic ecoregions, reaching in the Neotropic its highest diversity. There have been hints in previously published phylogenetic trees from mitochondrial genome, nuclear rRNA, from combinations of both and morphology that the Australasian Amblyomma or the Australasian Amblyomma plus the Amblyomma species from the southern cone of South America, might be sister-group to the Amblyomma of the rest of the world. However, a stable phylogenetic framework of Amblyomma for a better understanding of the biogeographic patterns underpinning its diversification is lacking. Methods We used genomic techniques to sequence complete and nearly complete mitochondrial genomes –ca. 15 kbp– as well as the nuclear ribosomal cluster –ca. 8 kbp– for 17 Amblyomma ticks in order to study the phylogeny and biogeographic pattern of the genus Amblyomma, with particular emphasis on the Neotropical region. The new genomic information generated here together with genomic information available on 43 ticks (22 other Amblyomma species and 21 other hard ticks–as outgroup–) were used to perform probabilistic methods of phylogenetic and biogeographic inferences and time-tree estimation using biogeographic dates. Results In the present paper, we present the strongest evidence yet that Australasian Amblyomma may indeed be the sister-group to the Amblyomma of the rest of the world (species that occur mainly in the Neotropical and Afrotropical zoogeographic regions). Our results showed that all Amblyomma subgenera (Cernyomma, Anastosiella, Xiphiastor, Adenopleura, Aponomma and Dermiomma) are not monophyletic, except for Walkeriana and Amblyomma. Likewise, our best biogeographic scenario supports the origin of Amblyomma and its posterior diversification in the southern hemisphere at 47.8 and 36.8 Mya, respectively. This diversification could be associated with the end of the connection of Australasia and Neotropical ecoregions by the Antarctic land bridge. Also, the biogeographic analyses let us see the colonization patterns of some neotropical Amblyomma species to the Nearctic. Conclusions We found strong evidence that the main theater of diversification of Amblyomma was the southern hemisphere, potentially driven by the Antarctic Bridge's intermittent connection in the late Eocene. In addition, the subgeneric classification of Amblyomma lacks evolutionary support. Future studies using denser taxonomic sampling may lead to new findings on the phylogenetic relationships and biogeographic history of Amblyomma genus. Graphical Abstract

Abstract Emotion recognition shows large inter-individual variability, and is substantially affected by childhood trauma as well as modality, emotion portrayed, and intensity. While research suggests childhood trauma influences emotion recognition, it is unclear whether this effect is consistent when controlling for interrelated individual differences. Further, the universality of the effects has not been explored, most studies have not examined differing modalities or intensities. This study examined childhood trauma’s association with accuracy, when controlling for alexithymia and psychopathy traits, and if this varied across modality, emotion portrayed, and intensity. An adult sample (N = 122) completed childhood trauma, alexithymia, and psychopathy questionnaires and three emotion tasks: faces, voices, audio-visual. When investigating childhood trauma alone, there was a significant association with poorer accuracy when exploring modality, emotion portrayed, and intensity. When controlling for alexithymia and psychopathy, childhood trauma remained significant when exploring emotion portrayed, however, it was no longer significant when exploring modality and intensity. In fact, alexithymia was significant when exploring intensity. The effect sizes overall were small. Our findings suggest the importance of controlling for interrelated individual differences. Future research should explore more sensitive measures of emotion recognition, such as intensity ratings and sensitivity to intensity, to see if these follow accuracy findings.

Abstract The skin is the primary feeding site of ticks that infest livestock animals such as cattle. The highly specialised functions of skin at the molecular level may be a factor contributing to variation in susceptibility to tick infestation; but these remain to be well defined. The aim of this study was to investigate the bovine skin transcriptomic profiles of tick-naïve and tick-infested cattle and to uncover the gene expression networks that influence contrasting phenotypes of host resistance to ticks. RNA-Seq data was obtained from skin of Brangus cattle with high (n = 5) and low (n = 6) host resistance at 0 and 12 weeks following artificial tick challenge with Rhipicephalus australis larvae. No differentially expressed genes were detected pre-infestation between high and low resistance groups, but at 12-weeks there were 229 differentially expressed genes (DEGs; FDR

Abstract Major depressive disorder (MDD) is marked by altered processing of emotional stimuli, including facial expressions. Recent neuroimaging research has attempted to investigate how these stimuli alter the directional interactions between brain regions in those with MDD; however, methodological heterogeneity has made identifying consistent effects difficult. To address this, we systematically examined studies investigating MDD-associated differences present in effective connectivity during the processing of emotional facial expressions. We searched five databases: PsycINFO, EMBASE, PubMed, Scopus, and Web of Science, using a preregistered protocol (registration number: CRD42021271586). Of the 510 unique studies screened, 17 met our inclusion criteria. These studies identified that compared with healthy controls, participants with MDD demonstrated (1) reduced connectivity from the dorsolateral prefrontal cortex to the amygdala during the processing of negatively valenced expressions, and (2) increased inhibitory connectivity from the ventromedial prefrontal cortex to amygdala during the processing of happy facial expressions. Most studies investigating the amygdala and anterior cingulate cortex noted differences in their connectivity; however, the precise nature of these differences was inconsistent between studies. As such, commonalities observed across neuroimaging modalities warrant careful investigation to determine the specificity of these effects to particular subregions and emotional expressions. Future research examining longitudinal connectivity changes associated with treatment response may provide important insights into mechanisms underpinning therapeutic interventions, thus enabling more targeted treatment strategies.

Abstract Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Abstract Loss of genetic diversity in elite crop breeding pools can severely limit long‐term genetic gains and limit ability to make gains in new traits, like heat tolerance, that are becoming important as the climate changes. Here, we investigate and propose potential breeding program applications of optimal haplotype stacking (OHS), a selection method that retains useful diversity in the population. OHS selects sets of candidates containing, between them, haplotype segments with very high segment breeding values for the target trait. We compared the performance of OHS, a similar method called optimal population value (OPV), truncation selection on genomic estimated breeding values (GEBVs), and optimal contribution selection (OCS) in stochastic simulations of recurrent selection on founder wheat genotypes. After 100 generations of intercrossing and selection, OCS and truncation selection had exhausted the genetic diversity, while considerable diversity remained in the OHS population. Gain under OHS in these simulations ultimately exceeded that from truncation selection or OCS. OHS achieved faster gains when the population size was small, with many progeny per cross. A promising hybrid strategy, involving a single cycle of OHS in the first generation followed by recurrent truncation selection, substantially improved long‐term gain compared with truncation selection and performed similarly to OCS. The results of this study provide initial insights into where OHS could be incorporated into breeding programs.

Shallow water Antarctic marine macroepifaunal assemblages live in one of the most naturally disturbed marine environments due to the impact of icebergs scouring the seafloor. They are, however, amongst the least anthropogenically impacted assemblages and are afforded protection under the Antarctic Treaty system. When the British Antarctic Survey’s Rothera Research Station wharf needed extending to accommodate the newly constructed UK polar research vessel, the RRS Sir David Attenborough, a Comprehensive Environmental Evaluation (CEE) was conducted to assess the impact. The macroepifaunal likely to be impacted by the construction was surveyed through ROV videos of five transects, centered on the middle of the construction zone, from 10–100 m deep. A pre-construction survey was completed in March 2017, as part of the CEE impact assessment, and a post-build survey in 2022 (delayed from 2021, and reduced in scope, due to the COVID-19 pandemic). Sedimentation rates were also measured before and during construction and were high during the second summer when the wharf pilings were being back filled with crushed rock. The measured differences between pre- and post-construction assemblages were minor and were not reflected in the overall number of taxa (operational taxonomic units – OTU), or diversity, but there were subtle shifts in species composition. The largest differences in the macroepifauna were a reduction in the number of the common urchin, Sterechinus neumayeri, and seastar, Odontaster validus, and were within expected variability. The small changes detected in the macroepifauna indicate it was minimally impacted and/or recovered in the subsequent two years, therefore during wharf construction the accompanying mitigation measures were robust.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.MethodsA multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.FindingsA total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score 60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Abstract Lowland grassland fragments in southeast Australia are valued for both sheep grazing and conservation. Many fragments are now rarely burnt, despite being shaped by millennia of Aboriginal fire‐use. Restoring fire could potentially reduce fuels, control exotic plant species, promote native species and renew Aboriginal cultural burning. However, this requires understanding of how fire and large herbivores, both native and exotic, are coupled and influence vegetation. We implemented a single round of low‐intensity experimental burns in an area of remnant grassland and patchy eucalypt woodlands in Tasmania that is managed for conservation, albeit intermittently grazed by sheep, as well as by native and exotic wild herbivores. We compared herbivore activity between burnt and unburnt areas over 2 years using cameras and scat transects, and assessed how fire and herbivory influenced herbaceous biomass and the cover of broad vegetation classes with and without herbivore exclusion. Contrary to expectations, burnt areas did not disproportionately attract the main herbivores: domestic sheep, introduced deer and native wallabies. In the predominant grassy sward, grazing and fire both reduced herbaceous biomass but we found no support for our hypothesis that grazing reduces biomass more strongly after burning. This contrasts with isolated patches of Poa tussock grassland, where fire reduced biomass much more strongly than grazing, and grazing effects on biomass were more pronounced following burning. The cover of broad vegetation classes was little affected by burning, but excluding herbivores increased exotic grass cover in both burnt and unburnt plots. Practical implication. In degraded fragments of lowland native grassland, burning and grazing do not necessarily act as strongly synergistic disturbances. Grazing by sheep and wild herbivores can help to control exotic grasses and reduce herbaceous biomass, although burning is much more effective than grazing for reducing biomass of unpalatable Poa tussock grassland. Our results suggest that returning occasional low‐intensity fires to our study system, and other degraded grassland‐woodland fragments, can be compatible with livestock production and conservation goals, but this requires caution and adaptive management.

Purpose: The landmark randomized trial on chest irradiation in extensive disease small cell lung cancer (CREST) demonstrated that consolidative thoracic radiation therapy (cTRT) improved overall (OS) and progression-free survival (PFS) after initial chemotherapy (chemo) in extensive-stage small cell lung cancer, with potentially increased benefit in women compared with men. It is unknown whether similar findings would apply after chemoimmunotherapy became the standard first-line treatment. In this analysis, we report national practice patterns and survival outcomes of cTRT according to patient sex. Methods and Materials: We included patients from de-identified electronic health record-derived database diagnosed with stage IV small cell lung cancer (2014-2021) who completed 4 to 6 cycles of first-line systemic therapy (platinum-doublet chemotherapy or chemoimmunotherapy). We evaluated OS and PFS using multivariable Cox proportional hazards regression with receipt of cTRT as an independent variable and stratified by sex. As a sensitivity analysis, we weighted the models by the inverse probability of receiving cTRT. Results: A total of 1227 patients were included (850 chemotherapy, 377 chemoimmunotherapy). There were no statistically significant differences in baseline characteristics between patients who did and did not receive cTRT. Among women, cTRT was associated with superior OS (adjusted hazard ratio [HR], 0.67; 95% CI, 0.52-0.87) and PFS (HR, 0.63; 95% CI, 0.49-0.82) compared with those not receiving cTRT. Conversely, no OS or PFS benefit with cTRT was observed in men (OS HR, 1.03; 95% CI, 0.80-1.31; PFS HR, 1.12; 95% CI, 0.85-1.47). Findings were similar in weighted analyses. Conclusions: The survival efficacy of cTRT may be moderated by sex, with female patients appearing more likely to benefit than male patients. These findings reflect sex-based survival trends with similar effect sizes to those observed in the CREST trial. Although the underpinnings of this association need to be elucidated, stratification by sex should be considered for randomized-controlled trials studying cTRT in extensive-stage small cell lung cancer.

Abstract The brain’s default mode network has a central role in the processing of information concerning oneself. Dysfunction in this self-referential processing represents a key component of multiple mental health conditions, particularly social anxiety disorder (SAD). This case-control study aimed to clarify alterations to network dynamics present during self-appraisal in SAD participants. A total of 38 adolescents and young adults with SAD and 72 healthy control participants underwent a self-referential processing fMRI task. The task involved two primary conditions of interest: direct self-appraisal (thinking about oneself) and reflected self-appraisal (thinking about how others might think about oneself). Dynamic causal modeling and parametric empirical Bayes were then used to explore differences in the effective connectivity of the default mode network between groups. We observed connectivity differences between SAD and healthy control participants in the reflected self-appraisal but not the direct self-appraisal condition. Specifically, SAD participants exhibited greater excitatory connectivity from the posterior cingulate cortex (PCC) to medial prefrontal cortex (MPFC) and greater inhibitory connectivity from the inferior parietal lobule (IPL) to MPFC. In contrast, SAD participants exhibited reduced intrinsic connectivity in the absence of task modulation. This was illustrated by reduced excitatory connectivity from the PCC to MPFC and reduced inhibitory connectivity from the IPL to MPFC. As such, participants with SAD showed changes to afferent connections to the MPFC which occurred during both reflected self-appraisal as well as intrinsically. The presence of connectivity differences in reflected and not direct self-appraisal is consistent with the characteristic fear of negative social evaluation that is experienced by people with SAD.

Aims: The Karstveld in Namibia has been recognized as an area of high plant diversity. However, this area is also recognised as a hotspot of various forms of degradation including bush encroachment. Minimal baseline data on the composition and diversity of vegetation in this area is available, therefore this paper is a first attempt to rectify this data deficiency. Study area: The Karstveld in Namibia is formed around the Otavi Mountain Range in northern Central Namibia, consisting of strongly karstified carbonate bedrock, rising up to 2000 m a.s.l. The Karstveld includes the Ovambo Basin plains with shallow calcrete soils north of the range, up to the Omuramba Ovambo. Because of orographic effects, the area receives some of the highest rainfall in Namibia, with up to 600 mm per year. Methods: A set of 889 relevés with 868 species was selected from the GVID ID AF-NA-001 database. A partial data set, using trees, shrubs, dwarf shrubs and grasses only, was used for the classification with modified TWINSPAN. The initial result yielded four main groups, according to which the data was split and further classified. Several vegetation types observed during field surveys were not reflected in the classification results; these were refined using Cocktail with known characteristic species. Results: The four main units represented wetlands and grasslands with six associations, a Thornbush savanna – Karstveld transition zone with four associations, Kalahari vegetation with four associations and the Karstveld proper with eight associations. The latter are grouped together as the Terminalietea prunioides, with two orders and three alliances recognised under them. We describe 16 associations according to the ICPN. Conclusions: Although the associations presented in this paper are clearly defined, there exists a high degree of diversity within these. The Karstveld is also extraordinary species rich within the context of the arid to semi-arid Namibian environment. Taxonomic reference: Klaassen and Kwembeya (2013) for vascular plants, with the exception of the genus Acacia s.l. (Fabaceae), for which Kyalangalilwa et al. (2013) was followed. Abbreviations: ga = annual grass; gp = perennial grass; GPS = Global Positioning System, referring to a hand-held ground receiver; hl = herb layer, containing all hemicryptophytes, therophytes and geophytes, but excluding grasses (Poaceae); ICPN = International Code of Phytosociological Nomenclature (Theurillat et al. 2021); MAP = mean annual precipitation; NMS = nonmetric multidimensional scaling (Kruskal 1964); RDL = Red Data List (IUCN Species Survival Commission 2001); s1 = tall shrubs, i.e. multi-stemmed phanerophytes between 1 and 5 m; s2 = short shrubs, i.e. chamaephytes or ‘dwarf shrubs’ below 1 m; SOTER = Global and National Soils and Terrain Digital Database (FAO 1993); t1 = tall trees, > 10 m; t2 = short trees, between 5 and 10 m; t3 = low trees, i.e. single-stemmed phanerophytes between 2 and 5 m; TWINSPAN = Two Way Indicator Species Analysis (Roleček et al. 2009); WGS84 = World Geodetic System, 1984 ensemble.

Abstract Background It has been challenging to implement genomic selection in multi-breed tropical beef cattle populations. If commercial (often crossbred) animals could be used in the reference population for these genomic evaluations, this could allow for very large reference populations. In tropical beef systems, such animals often have no pedigree information. Here we investigate potential models for such data, using marker heterozygosity (to model heterosis) and breed composition derived from genetic markers, as covariates in the model. Models treated breed effects as either fixed or random, and included genomic best linear unbiased prediction (GBLUP) and BayesR. A tropically-adapted beef cattle dataset of 29,391 purebred, crossbred and composite commercial animals was used to evaluate the models. Results Treating breed effects as random, in an approach analogous to genetic groups allowed partitioning of the genetic variance into within-breed and across breed-components (even with a large number of breeds), and estimation of within-breed and across-breed genomic estimated breeding values (GEBV). We demonstrate that moderately-accurate (0.30–0.43) GEBV can be calculated using these models. Treating breed effects as random gave more accurate GEBV than treating breed as fixed. A simple GBLUP model where no breed effects were fitted gave the same accuracy (and correlations of GEBV very close to 1) as a model where GEBV for within-breed and the GEBV for (random) across-breed effects were included. When GEBV were predicted for herds with no data in the reference population, BayesR resulted in the highest accuracy, with 3% accuracy improvement averaged across traits, especially when the validation population was less related to the reference population. Estimates of heterosis from our models were in line with previous estimates from beef cattle. A method for estimating the number of effective breed comparisons for each breed combination accumulated across contemporary groups is presented. Conclusions When no pedigree is available, breed composition and heterosis for inclusion in multi-breed genomic evaluation can be estimated from genotypes. When GEBV were predicted for herds with no data in the reference population, BayesR resulted in the highest accuracy.

Tuberculosis, caused by the Mycobacterium tuberculosis (Mtb) bacteria, is one of the world’s deadliest infectious diseases. Despite being the world’s oldest pandemic, tuberculosis is very much a challenge of the modern era. In high-incidence settings, all people are at risk, irrespective of whether they have common vulnerabilities to the disease warranting the current WHO recommendations for community-wide tuberculosis active case finding in these settings. Despite good evidence of effectiveness in reducing tuberculosis transmission, uptake of this strategy has been lacking in the communities that would derive greatest benefit. We consider the various complexities in eliminating tuberculosis from the first principles of the disease, including diagnostic and other challenges that must be navigated under an elimination agenda. We make the case that community-wide tuberculosis active case finding is the best strategy currently available to drive elimination forward in high-incidence settings and that no time should be lost in its implementation. Recognizing that high-incidence communities vary in their epidemiology and spatiosocial characteristics, tuberculosis research and funding must now shift towards radically supporting local implementation and operational research in communities. This “preparing of the ground” for scaling up to community-wide intervention centers the local knowledge and local experience of community epidemiology to optimize implementation practices and accelerate reductions in community-level tuberculosis transmission.

Purpose: Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA) in two groups of males, either partially sleep-restricted (4 h) or with habitual sleep (8 h) for 2 nights, was beneficial for sleep and subsequent morning Stroop performance. Methods: Participants were randomly allocated to two independent groups who either had 4 h (33 males) or 8 h (36 males) sleep for two nights. Using a double-blinded, randomised counterbalanced design, they then completed five sessions, (i) two familiarisation sessions including 7 days of sleep and dietary intake, (ii) three conditions with 4 h or 8 h sleep and either NoPill control (NoPill), placebo (PLAC) or ZMA (ZMA). Sleep was assessed by actimetry and sleep questionnaires, and cognitive performance was assessed by the Stroop test. The data were analysed using a general linear model with repeated measures. Results: A main effect for “sleep” (4 or 8 h) was found, where more opportunity to sleep resulted in better “sleep” metrics (both objective and subjective) as well as better Stroop scores (lower colour-interference and word-interference scores and lower error in words). No main effect for “Pill” was found other than the mood state depression, where subjective ratings for the PLAC group were lower than the other two conditions. Interactions were found in anger, ease to sleep and waking time. Conclusion: Having 8 h opportunity to sleep resulted in better “sleep” metrics as well as better Stroop scores compared to 4 h. Supplementation of ZMA for 4 or 8 h for 2 nights had no effect on subsequent morning cognitive performance but reduced sleep or total sleep time by ~0.46 h compared to the other conditions. An interaction was found where sleep time was reduced by ~0.94 h in the ZMA group in the 8 h condition compared to NoPill or PLAC.

Abstract Temperate coastal marine waters are often thermally stratified from spring through fall but can be dynamic and disrupted by tidal currents and wind‐driven upwelling. These mixing events introduce deeper, cooler water with a higher partial pressure of CO2 (pCO2) and its associated microbial communities to the surface. Anecdotally, these events impact shellfish hatcheries and farms, warranting improved understanding of changes in composition and activity of marine microbial communities in relation to environmental processes. To characterize both compositional and functional changes associated with abiotic factors, here, we generate a reference metatranscriptome from the Strait of Georgia over representative seasons and analyze metatranscriptomic profiles of the microorganisms present within intake water containing different pCO2 levels at a shellfish hatchery in British Columbia from June through October. Abiotic factors studied include pH, temperature, alkalinity, aragonite, calcite, and pCO2. Community composition changes were observed to occur at broad taxonomic levels and most notably to vary with temperature and pCO2. Functional gene expression profiles indicated a strong difference between early (June–July) and late summer (August–October) associated with viral activity. The taxonomic data suggest this could be due to the termination of cyanobacteria and phytoplankton blooms by viral lysis in the late season. Functional analysis indicated fewer differentially expressed transcripts associated with abiotic variables (e.g., pCO2) than with the temporal effect. Microbial composition and activity in these waters vary with both short‐term effects observed alongside abiotic variation and long‐term effects observed across seasons. The analysis of both taxonomy and functional gene expression simultaneously in the same samples by environmental RNA (eRNA metatranscriptomics) provided a more comprehensive view for monitoring water bodies than either would in isolation.

Abstract Loneliness and social isolation, experienced more long-term, has been shown to increase mortality and lead to poorer health outcomes in specific cohorts. However, it is unclear what the prevalence of chronic loneliness and social isolation is, and which demographic groups are most at risk of reporting more chronic forms. A psychometrically validated classification system was used to identify people who met criteria for episodic and chronic loneliness and social isolation using the Household Income and Labour Dynamics in Australia (HILDA) survey waves 14–18. The prevalence of loneliness (overall 34%; 21% episodic, 13% chronic) far exceeded that of social isolation (overall 17%; 13% episodic, 4% chronic). There was consistency in the demographic characteristics (from age, sex, household type, income) of those who experienced loneliness and social isolation. However, people with a long-term health condition had an elevated risk of episodic loneliness (AOR 1.24, 95% CI 1.11–1.39) and a markedly higher risk of chronic loneliness (AOR 2.01, 95% CI 1.76–2.29), compared with those without a long-term health condition. Loneliness, both episodic and chronic subtypes, is more prevalent than social isolation. However, both chronic loneliness and social isolation remains neglected and poorly targeted within current practice and policy.

Rhodium is one of the scarcest, most valuable, and useful platinum group metals, a strategically important material relied on heavily by automotive and electronics industries. The limited finite natural sources of Rh and exponentially increasing demands on these supplies mean that new sources are being sought to stabilise supplies and prices. Spent nuclear fuel (SNF) contains a significant quantity of Rh, though methods to recover this are purely conceptual at this point, due to the differing chemistry between SNF reprocessing and the methods used to recycle natural Rh. During SNF reprocessing, Rh partitions between aqueous nitric acid streams, where its speciation is complex, and insoluble fission product waste streams. Various techniques have been investigated for Rh recovery during SNF reprocessing for over 50 years, including solvent extraction, ion exchange, precipitation, and electrochemical methods, with tuneable approaches such as impregnated composites and ionic liquids receiving the most attention recently, assisted by more the comprehensive understanding of Rh speciation in nitric acid developed recently. The quantitative recovery of Rh within the SNF reprocessing ecosystem has remained elusive thus far, and as such, this review discusses the recent developments within the field, and strategies that could be applied to maximise the recovery of Rh from SNF.

Abstract Objective To assess the safety and utility of a pragmatic clinical algorithm to guide rational antibiotic use in children presenting with respiratory infection. Methods The effect of an algorithm to guide the management of young (

Abstract Background Poor oral health literacy has been proposed as a causal factor in disparities in oral health outcomes. This study aims to investigate oral health literacy (OHL) in a socially and culturally diverse population of Australian adults visiting a public dental clinic in Western Sydney. Methods A mixed methods study where oral health literacy was assessed using the Health Literacy in Dentistry scale (HeLD-14) questionnaire and semi-structured interviews explored oral health related knowledge, perceptions and attitudes. Interviews were analysed using a thematic approach. Results A sample of 48 participants attending a public dental clinic in Western Sydney was recruited, with a mean age of 59.9 (SD16.2) years, 48% female, 50% born in Australia, 45% with high school or lower education, and 56% with low-medium OHL. A subgroup of 21 participants with a mean age of 68.1 (SD14.6) years, 40% female, 64% born in Australia, 56% with a high school or lower education, and 45% with low-medium OHL completed the interview. Three themes identified from the interviews included 1) attitudes and perceptions about oral health that highlighted a lack of agency and low prioritisation of oral health, 2) limited knowledge and education about the causes and consequences of poor oral health, including limited access to oral health education and finally 3) barriers and enablers to maintaining good oral health, with financial barriers being the main contributor to low OHL. Conclusions Strategies aimed at redressing disparities in oral health status should include improving access to oral health information. The focus should be on the impact poor oral health has on general health with clear messages about prevention and treatment options in order to empower individuals to better manage their oral health.

Abstract Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.

Abstract Genomic selection in sugarcane faces challenges due to limited genomic tools and high genomic complexity, particularly because of its high and variable ploidy. The classification of genotypes for single nucleotide polymorphisms (SNPs) becomes difficult due to the wide range of possible allele dosages. Previous genomic studies in sugarcane used pseudo‐diploid genotyping, grouping all heterozygotes into a single class. In this study, we investigate the use of continuous genotypes as a proxy for allele‐dosage in genomic prediction models. The hypothesis is that continuous genotypes could better reflect allele dosage at SNPs linked to mutations affecting target traits, resulting in phenotypic variation. The dataset included genotypes of 1318 clones at 58K SNP markers, with about 26K markers filtered using standard quality controls. Predictions for tonnes of cane per hectare (TCH), commercial cane sugar (CCS), and fiber content (Fiber) were made using parametric, non‐parametric, and Bayesian methods. Continuous genotypes increased accuracy by 5%–7% for CCS and Fiber. The pseudo‐diploid parametrization performed better for TCH. Reproducing kernel Hilbert spaces model with Gaussian kernel and AK4 (arc‐cosine kernel with hidden layer 4) kernel outperformed other methods for TCH and CCS, suggesting that non‐additive effects might influence these traits. The prevalence of low‐dosage markers in the study may have limited the benefits of approximating allele‐dosage information with continuous genotypes in genomic prediction models. Continuous genotypes simplify genomic prediction in polyploid crops, allowing additional markers to be used without adhering to pseudo‐diploid inheritance. The approach can particularly benefit high ploidy species or emerging crops with unknown ploidy.

Objectives Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack).Design Diagnostic Test Accuracy study.Setting Six UK hospitals.Methods The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges.Results Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers.Conclusions Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose.Trial registration number ISRCTN79058224.

The hemophilias are the most common severe inherited bleeding disorders and are caused by deficiency of clotting factor (F) VIII (hemophilia A) or FIX (hemophilia B). The resultant bleeding predisposition significantly increases morbidity and mortality. The ability to improve the bleeding phenotype with modest increases in clotting factor levels has enabled the development and regulatory approval of adeno-associated viral (AAV) vector gene therapies for people with hemophilia A and B. The canine hemophilia model has proven to be one of the best predictors of therapeutic response in humans. Here, we report long-term follow-up of 12 companion dogs with severe hemophilia that were treated in a real-world setting with AAV gene therapy. Despite more baseline bleeding than in research dogs, companion dogs demonstrated a 94% decrease in bleeding rates and 61% improvement in quality of life over a median of 4.1 years (range 2.6–8.9). No new anti-transgene immune responses were detected; one dog with a pre-existing anti-FVIII inhibitor achieved immune tolerance with gene therapy. Two dogs expressing 1%–5% FVIII post gene therapy experienced fatal bleeding events. These data suggest AAV liver-directed gene therapy is efficacious in a real-world setting but should target expression >5% and closely monitor those with levels in the 1%–5% range.

Purpose: To present a rare case of dedifferentiated liposarcoma of the orbit. Observations: A 61-year-old male complained of left-sided proptosis, diplopia, and limited ocular motility for two years. Biopsy results at that time were suggestive of an atypical lipomatous neoplasm. Ten years later, he presented with increase in size of the mass and worsening of his symptoms. Imaging showed a multi-lobulated mass in the left orbit involving the intraconal, medial, and anterior orbit. Decompression and orbitotomy with biopsy were performed to debulk the mass. Pathology showed a low-grade well-differentiated liposarcoma and the patient was monitored thereafter annually. Eight years later, he complained of persistent proptosis and mass effect from the tumor resulting in ptosis and diplopia and underwent orbital exenteration. Histopathological analysis of the exenterated orbit revealed a focal area of dedifferentiated liposarcoma. Conclusions and importance: Dedifferentiation of an orbital mass can occur as a late complication years after the diagnosis of well-differentiated liposarcoma. Compared to the previously published cases of orbital liposarcoma, this presentation shows a prolonged timeline prior to dedifferentiation (18 years after initial diagnosis). Symptoms of growth or invasive features could indicate dedifferentiation and should warrant a biopsy.