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Abstract Background Ecological and physical conditions vary with depth in aquatic ecosystems, resulting in gradients of habitat suitability. Although variation in vertical distributions among individuals provides evidence of habitat selection, it has been challenging to disentangle how processes at multiple spatio-temporal scales shape behaviour. Methods We collected thousands of observations of depth from $$>~300$$ > 300 acoustically tagged adult Chinook salmon Oncorhynchus tshawytscha, spanning multiple seasons and years. We used these data to parameterize a machine-learning model to disentangle the influence of spatial, temporal, and dynamic oceanographic variables while accounting for differences in individual condition and maturation stage. Results The top performing machine learning model used bathymetric depth ratio (i.e., individual depth relative to seafloor depth) as a response. We found that bathymetry, season, maturation stage, and spatial location most strongly influenced Chinook salmon depth. Chinook salmon bathymetric depth ratios were deepest in shallow water, during winter, and for immature individuals. We also identified non-linear interactions among covariates, resulting in spatially-varying effects of zooplankton concentration, lunar cycle, temperature and oxygen concentration. Conclusions Our results suggest Chinook salmon vertical habitat use is a function of ecological interactions, not physiological constraints. Temporal and spatial variation in depth distributions could be used to guide management decisions intended to reduce fishery impacts on Chinook salmon. More generally, our findings demonstrate how complex interactions among bathymetry, seasonality, location, and life history stage regulate vertical habitat selection.

Objective This study determined fermentation characteristics of commonly used feedstuffs, especially tropical roughages, for dairy cattle in Southeast Asia. This information is considered relevant in the context of the observed low milk fat content and milk production in Southeast Asia countries. Methods A total of 29 feedstuffs commonly used for dairy cattle in Vietnam and Thailand were chemically analysed and subjected to an in vitro gas production (GP) test. For 72 h, GP was continuously recorded with fully automated equipment and methane (CH4) was measured at 0, 3, 6, 9, 12, 24, 30, 36, 48, 60, and 72 h of incubation. A triphasic, nonlinear, regression procedure was applied to analyse GP profiles while a monophasic model was used to obtain kinetics related to CH4 production. Results King grass and VA06 showed a high asymptotic GP related to the soluble- and non-soluble fractions (i.e. A1 and A2, respectively) and had the highest acetate to propionate ratio in the incubation fluid. The proportion of CH4 produced (% of GP at 72 h) was found to be not different (p>0.05) between the various grasses. Among the selected preserved roughages (n = 6) and whole crops (n = 4), sorghum was found to produce the greatest amount of gas in combination with a relatively low CH4 production. Conclusion Grasses belonging to the genus Pennisetum, and whole crop sorghum can be considered as suitable ingredients to formulate dairy rations to enhance milk fat content in Vietnam/Thailand.

Background: Trauma-focused treatments for post-traumatic stress disorder (PTSD) are effective for many patients. However, relapse may occur when acquired extinction memories fail to generalize beyond treatment contexts. A subgroup of PTSD patients – potentially with substantial exposure to early-life adversity (ELA) – show dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which results in lower cortisol levels. Glucocorticoids, including cortisol, appear to facilitate strength and generalization of emotional memories.Objective: We describe the protocol of an integrated PTSD study. We investigate (A) associations between HPA-axis dysregulation, ELA, epigenetic markers, and PTSD treatment outcome (observational study); and (B) effects of exogenous glucocorticoids on strength and generalization of extinction memories and associated neural mechanisms [pharmacological intervention study with functional magnetic resonance imaging (fMRI)]. The objective is to provide proof of concept that PTSD patients with HPA-axis dysregulation often experienced ELA and may show improved strength and generalization of extinction learning after glucocorticoid administration.Method: The observational study (n = 160 PTSD group, n = 30 control group) assesses ELA, follow-up PTSD symptoms, epigenetic markers, and HPA-axis characteristics (salivary cortisol levels during low-dose dexamethasone suppression test and socially evaluated cold-pressor test). The pharmacological intervention study (n = 80 PTSD group, with and without HPA-axis dysregulation) is a placebo-controlled fMRI study with a crossover design. To investigate strength and generalization of extinction memories, we use a differential fear acquisition, extinction, and extinction recall task with spatial contexts within a virtual environment. Prior to extinction learning, 20 mg hydrocortisone or placebo is administered. During next-day recall, strength of the extinction memory is determined by recovery of skin conductance and pupil dilation differential responding, whereas generalization is assessed by comparing responses between different spatial contexts.Conclusion: The integrated study described in the current protocol paper could inform a personalized treatment approach in which these PTSD patients may receive glucocorticoids as a treatment enhancer in trauma-focused therapies.Trial registration: The research project is registered in the European Union Drug Regulating Authorities Clinical Trials (EudraCT) database, https://eudract.ema.europa.eu/, EudraCT number 2020-000712-30.

ABSTRACTThis phase-3, double-blind, placebo-controlled study (NCT04228783) evaluated lot-to-lot consistency of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Participants were randomized (6:6:6:1) to receive the two-dose regimen from three consecutively manufactured lots of Ad26.ZEBOV on Day 1 paired with three consecutively manufactured lots of MVA-BN-Filo on Day 57 (Groups 1–3) or two doses of placebo (Group 4). An additional cohort also received an Ad26.ZEBOV booster or placebo 4 months post-dose 2. Equivalence of the immunogenicity at 21 days post-dose 2 between any two groups was demonstrated if the 95% confidence interval (CI) of the Ebola virus glycoprotein (EBOV GP)–binding antibody geometric mean concentration (GMC) ratio was entirely within the prespecified margin of 0.5–2.0. Lot-to-lot consistency (i.e., consecutive lots can be consistently manufactured) was accomplished if equivalence was shown for all three pairwise comparisons. Results showed that the primary objective in the per-protocol immunogenicity subset (n = 549) was established for each pairwise comparison (Group 1 vs 2: GMC ratio = 0.9 [95% CI: 0.8, 1.1], Group 1 vs 3: 0.9 [0.8, 1.1], Group 2 vs 3: 1.0 [0.9, 1.2]). Equivalence of the three groups for the Ad26.ZEBOV component only was also demonstrated at 56 days post-dose 1. EBOV GP–binding antibody responses (post-vaccination concentrations >2.5-fold from baseline) were observed in 419/421 (99.5%) vaccine recipients at 21 days post-dose 2 and 445/460 (96.7%) at 56 days post-dose 1. In the booster cohort (n = 39), GMCs increased 9.0- and 11.8-fold at 7 and 21 days post-booster, respectively, versus pre-booster. Ad26.ZEBOV, MVA-BN-Filo was well tolerated, and no safety issues were identified.

Measuring immune correlates of disease acquisition and protection in the context of a clinical trial is a prerequisite for improved vaccine design. We analysed binding and neutralizing antibody measurements 4 weeks post vaccination as correlates of risk of moderate to severe-critical COVID-19 through 83 d post vaccination in the phase 3, double-blind placebo-controlled phase of ENSEMBLE, an international randomized efficacy trial of a single dose of Ad26.COV2.S. We also evaluated correlates of protection in the trial cohort. Of the three antibody immune markers we measured, we found most support for 50% inhibitory dilution (ID50) neutralizing antibody titre as a correlate of risk and of protection. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; P = 0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43%, 72%) at non-quantifiable ID50 (

The tacit practical knowledge of psychologists and support staff to foster a real connection between support staff and people with intellectual disabilities and challenging behaviour was explored. Therefore, six dyads comprising individuals with intellectual disabilities and challenging behaviour and their support staff were video recorded during joint engagement in an activity. To tap into the implicit knowledge of professionals about when staff have 'a real connection' with a person with an intellectual disability, 10 psychologists and 10 support staff were asked to pinpoint these moments in the pre-recorded video compilation. They also shared their interpretations about what they considered to be a real connection. The results displayed that participants designated real connections as occurring when they noticed concrete interactions taking place. Based on thematic analysis of the data, four themes were identified that encapsulated what professionals deemed to be a real connection. In conclusion: joint engagement in an activity appears to be a context that fosters opportunities for real connection. Furthermore, support staff should adopt a sensitive attitude and create a safe atmosphere, to establish real connections.

Offshore solar is seen as a promising technology for renewable energy generation. It can be particularly valuable when co-located within offshore wind farms, as these forms of energy generation are complementary. However, the environmental impact of offshore solar is not fully understood yet, and obtaining a better understanding of the possible impact is essential before this technology is applied at a large scale. An important aspect which is still unclear is how offshore solar affects the local hydrodynamics in the marine environment. This article describes the hydrodynamic wake generated by an offshore solar array, arising from the interaction between the array and a tidal current. A computational fluid dynamic (CFD) modeling approach was used, which applies numerical large eddy simulations (LES) in OpenFOAM. The simulations are verified using the numerical model TUDFLOW3D. The study quantifies the wake dimensions and puts them in perspective with the array size, orientation, and tidal current magnitude. The investigation reveals that wake width depends on array size and array orientation. When the array is aligned with the current, wake width is relatively confined and does not depend on the array size. When the array is rotated, the wake width experiences exponential growth, becoming approximately 30% wider than the array width. Wake length is influenced by factors such as horizontal array dimensions and current magnitude. The gaps in between the floaters decrease this dependency. Similarly, the wake depth showed similar dependencies, except for the current magnitude, and only affected the upper meters of the water column. Beneath the array, flow shedding effects occur, affecting a larger part of the water column than the wake. Flow shedding depends on floater size, gaps, and orientation.

IntroductionThe prevalence, pervasiveness, and minimization of sexual harassment and sexual assault (SHSA) within the Western Australian mining industry has been revealed in recent Australian reports and inquiries. However, there remains a gap in scholarship focusing on SHSA within the mining sector, specifically that engages with mining employees to understand this issue.MethodsThis study aimed to fill this gap by exploring the experiences and perspectives of Western Australian mining employees in relation to SHSA. Through qualitative research methods, stakeholders (n = 30) from various industry roles (e.g., front-line operations, administrative staff) participated in semi-structured interviews. A deductive thematic analysis was conducted to analyze the data.ResultsThe study revealed diverse perspectives of SHSA among participants, highlighting how this issue is understood, addressed, and discussed within the workplace. While some participants recognized positive shifts in workplace culture, it became apparent that additional efforts are needed to tackle the underlying and persistent factors that contribute to sexism, misogyny, and, ultimately, SHSA. Participants shared their perspectives regarding strategies and initiatives that could effectively combat SHSA within the industry.DiscussionThis study constitutes a significant contribution to the limited body of research on SHSA in the Western Australian mining sector, offering valuable insights and recommendations for future prevention initiatives.

Background. Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. However, long-term graft survival remains a challenge. The enzyme indoleamine 2,3 dioxygenase (IDO) has been reported to have immunomodulatory effects with IDO transcripts being elevated in both antibody-mediated rejection and T cell–mediated rejection. Methods. A metal-conjugated antibody panel for the staining of kidney biopsies was developed, allowing the visualization of 41 structural and immune markers on a single tissue slide to gain in-depth insight into the composition and localization of the immune cell compartment. Staining was applied to week 4 and 24 protocol biopsies of 49 patients as well as on 15 indication biopsies of the TRITON study and 4 additional transplantation biopsies with glomerulitis. Results. A highly distinctive and specific glomerular IDO expression was observed in biopsies from 3 of 49 patients in imaging mass cytometry. Immunohistochemistry confirmed IDO expression in glomeruli of 10 of 10 cases with glomerulitis. IDO was found to be expressed by CD31+ glomerular endothelial cells, accompanied by the presence of granzyme-B+Tbet+CD7+CD45RA+ natural killer cells and CD68+ macrophages. Furthermore, a proportion of both the immune cells and endothelial cells expressed Ki-67, indicative of cell proliferation, which was not observed in control glomeruli. Conclusions. Our results show glomerular IDO expression in transplanted kidneys with glomerulitis, which is accompanied by increased numbers of natural killer cells and macrophages and likely reflects local immune activation.

Direct comparisons are made between the crystallographic texture and residual stress distribution within two otherwise identical Inconel cubes produced by Selective Laser Melting (SLM) and Electron Beam Melting (EBM) additive manufacturing processes. In both respects, significant differences were observed; the SLM process produced a sample with high residual stress and cubic texture, while the EBM process generated negligible residual stress and a fibre texture. In the case of the SLM sample, the paper continues on to examine two different approaches to modelling the residual stress field; 1. a simplistic version based on an assumed radially symmetric isotropic eigenstrain, and 2. a layer-by-layer combined thermo-mechanical approach based on finite element modelling. Both models were able to capture the important overall features of the residual stress distribution, however the layer-by-layer approach showed more fidelity in the finer details.

Abstract Therapies for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) include balloon pulmonary angioplasty (BPA) and PH‐specific medical therapy. This study compares survival and its predictors before and after the introduction of BPA. BPA was independently associated with survival; however, there was no difference in overall survival between the two cohorts.

The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) can be associated with significant toxicity. We performed a systematic review and meta-analysis of the toxicity of combination treatment of ICIs with TKIs (ICI + TKI) in clinical trials with solid organ malignancies. Our primary endpoint explored the incidence of grade 3 - 5 (G3-5) treatment-related toxicity and our secondary endpoints included the incidence of toxicity by treatment type, disease type and studies with run-in strategies. A total of 9750 abstracts were identified, of which 72 eligible studies were included. The most common disease types were non-small cell lung cancer (n=8, 11.1%), renal cell carcinoma (n=10, 13.8%) and hepatobiliary cancers (n=10, 13.8%). The overall incidence of G3-5 toxicity was 56% (95% CI = 50% – 61%). The most common TKIs combined with ICIs in this analysis were multi-targeted TKIs (n = 52, 72%), VEGF specific (n = 9, 12.5%), or oncogene-targeting TKIs (EGFR, ALK, BRAF, MEK) (n =11, 15.3%). Oncogene-targeted TKIs were associated a higher incidence of rashes and immune related adverse events (irAEs) and lower incidence of hypertension. In studies which used a TKI ‘run-in’ to mitigate toxicity, the pooled estimate of G3-5 toxicity was 71% (95% CI 57-81%). Almost half of studies (48%) omitted the incidence of G3-5 irAEs. Our work suggests that the majority of patients who receive ICI-TKI combinations will experience high grade toxicity (G3-G5) and that toxicity may be specific to TKI partner (Oncogene targeted TKIs: Rash, irAEs; VEGF/Multitargeted: Hypertension). These data did not suggest that a TKI ‘run-in’ was associated with a lower incidence of G3-5 toxicity. Reporting of irAEs was inconsistent supporting the need for harmonisation of adverse event reporting to include onset, duration and treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022367416.

Aims Low mood is a common clinical symptom during the perimenopause and menopause. However, the extent to which low mood in menopausal women intersects with thoughts of self-harm and suicidal ideation is largely unknown. In this study we aimed to explore these questions by using two different validated symptom scores. Methods We administered a modified version of the Greene Climacteric Symptom Questionnaire (Greene 1976) to all new patients attending the Newson Health Menopause and Wellbeing Clinic, Stratford-upon-Avon, between 1 September 2023 and 31 December 2023. Patients were also asked to complete the PHQ-9 symptom questionnaire, an instrument for diagnosing and measuring the severity of depression. Data were collected from electronic health records and analysed using descriptive statistics. Results 1,212 patients were included in the study and completed the Greene Climacteric and PHQ-9 questionnaires at baseline and after 3 months. Mood and mental health symptoms including self-reported anxiety and depression affected 98% of patients. 16% of respondents indicated that they had thoughts of self-harm or suicidal ideation on at least some days in the 2 weeks prior to their initial appointment (Question 9 of the PHQ-9). Conclusion The findings of our study demonstrate that negative mood symptoms are common in perimenopausal and menopausal women. 1 in 6 women reported thoughts of self-harm prior to initiation of HRT. Our observational data suggest that mood symptoms are highly prevalent and some women have severe symptoms and may experience suicidal ideation. Our findings should inform better mental health support and access to treatment for women experiencing negative mood symptoms in the menopause transition.

BackgroundParkinson’s disease is associated with increased impulsivity, which can be divided into several domains: motor (consisting of proactive and reactive subdomains), reflection, and cognitive impulsivity. Evidence suggests that both dopaminergic medication and subthalamic nucleus deep brain stimulation can affect impulsivity. Therefore, we set out to investigate the effects of dopaminergic medication and subthalamic nucleus deep brain stimulation on motor, reflection, and cognitive impulsivity in Parkinson’s disease patients.MethodsTwenty Parkinson’s disease patients who underwent subthalamic nucleus deep brain stimulation were tested ON and OFF dopaminergic medication and ON and OFF subthalamic nucleus deep brain stimulation. They performed three different impulsivity tasks: the AX continuous performance task (AX-CPT) to test for motor impulsivity, the Beads task for reflection impulsivity, and the Delay discounting task for cognitive impulsivity.ResultsThe combination of subthalamic nucleus deep brain stimulation and dopaminergic medication led to an increase in motor impulsivity (p = 0.036), both proactive (p = 0.045) and reactive (p = 0.006). There was no effect of either dopaminergic medication or subthalamic nucleus deep brain stimulation on reflection and cognitive impulsivity.ConclusionThe combination of dopaminergic medication and subthalamic nucleus deep brain stimulation leads to increased motor, but not cognitive or reflection, impulsivity in patients with Parkinson’s disease. Both proactive and reactive motor impulsivity were impaired by the combination of dopaminergic medication and subthalamic nucleus deep brain stimulation.

ABSTRACT: Dietary ingredient and nutrient composition may affect the efficacy of additives in broilers. Specific feed ingredients can represent dietary challenging conditions for broilers, resulting in impaired performances and health, which might be alleviated by dietary probiotics and postbiotics. We assessed the effects of a Lactobacilli probiotic (Pro) and postbiotic (Post) when added to a standard (SD) and challenge (CD) diet. A completely randomized block study with 2 diets (SD, CD) and 3 additive conditions (Control, Pro and Post) involving 1,368 one-day-old Ross male broilers, equally distributed among 36 pens, from d1 to d42 was conducted. Both diets were formulated to contain identical levels of nutrients, with CD formulated to be richer than SD in nonstarch polysaccharides using rye and barley as ingredients. Readout parameters included growth performance parameters, footpad lesions score, blood minerals and biochemical parameters, and tibia health, strength, and composition. Compared to SD, CD decreased BW (1,936 vs. 2,033 g; p = 0.001), increased FCR (p < 0.01) and impaired tibia health and strength (p < 0.05) at d35, thereby confirming the challenging effect of CD. Pro and Post increased BW in CD (+4.7 and +3.2%, respectively, at d35; P < 0.05) but not in the SD group, without affecting FCR. Independently of the diet, Pro increased plasma calcium, phosphorus and uric acid at d21 (+6.2, +7.4, and +15.5%, respectively) and d35 (+6.6, +6.2 and +21.0%, respectively) (P < 0.05) while Post increased plasma magnesium only at d21 (+11.3%; P = 0.037). Blood bile acids were affected by additives in an age- and diet-dependent manner, with some opposite effects between dietary conditions. Diet composition modulated Pro and Post effects on broiler growth performance. Additionally, Pro and Post affected animal metabolism and leg health diet-dependently for some but not all investigated parameters. Our findings show that the effects of pro- and postbiotics on the growth performance and physiology of broilers can be dependent on diet composition and thus possibly other factors affecting diet characteristics.

Massive Open Online Course (MOOC) integration into campus education is rising, in many different forms. When integrating MOOCs, motivation to learn demands consideration as it is related to academic achievement and well-being. Student motivation in formal integrated MOOC learning is understudied. This study aimed to characterize the shape of motivation to learn in integrated MOOC learning. Motivation profiles of undergraduate students that learn in three different MOOC integration designs were explored, as was the distribution of profiles among integration designs. Finally, factors that underpin motivation were compared between integration designs. Six motivation profiles were recovered through a two-step cluster analysis: Self-determined students, highly self-determined students, grade hunters, and teacher trusters who are moderately, highly, or extremely trusting. Proportions of motivation profiles differed significantly between MOOC integration designs, and psychological needs were satisfied and frustrated significantly different between designs. Implications for future MOOC integration research and practice are discussed.