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In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch's Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.

Abstract Automated delivery of therapy in virtual reality (VR) has the potential to be used for smoking cessation. Most obviously, it could be used to practise and establish alternative reactions to smoking cues. The first step in treatment development is to show that VR environments can trigger sufficient cravings in smokers. We evaluated a new VR public house outdoor scenario with 100 individuals who smoked daily. Participants were randomly assigned to the VR scenario with smoking cues or a neutral experience in VR. The VR experiences were presented in a standalone VR headset. Before and after VR, we collected self-reported craving scores for cigarettes and alcohol using the Tobacco Craving Questionnaire (TCQ) and visual analogue scales (VAS). Physiological data were also collected. Compared to the neutral condition, exposure to the smoking cues led to a large increase in craving for a cigarette (TCQ β = 11.44, p

Abstract The coronavirus (COVID-19) pandemic has caused financial hardship and psychological distress among young Australians. This study investigates whether the Australian Government’s emergency cash transfer payments—specifically welfare expansion for those unemployed prior to the pandemic (known in Australia as the Coronavirus Supplement) and JobKeeper (cash support for those with reduced or stopped employment due to the pandemic)—were associated with individual’s level of coping during the coronavirus pandemic among those with and without mental disorders (including anxiety, depression, ADHD and autism). The sample included 902 young adults who participated in all of the last three waves (8, 9C1, 9C2) of the Longitudinal Study of Australian Children (LSAC), a nationally representative cohort study. Modified Poisson regression models were used to assess the impact of emergency cash transfer payments on 18–22-year-old’s self-rated coping level, stratifying the analysis by those with and without mental disorders. All models were adjusted for gender, employment, location, family cohesion, history of smoking, alcohol intake, and COVID-19 test result. Of the 902-person sample analysed, 41.5% (n = 374) reported high levels of coping, 18.9% (n = 171) reported mental disorders, 40.3% (n = 364) received the Coronavirus Supplement and 16.4% (n = 148) received JobKeeper payments. Analysing the total sample demonstrated that participants who received the JobKeeper payment were more likely to have a higher level of coping compared to those who did not receive the JobKeeper payment. Stratified analyses demonstrated that those with pre-existing mental disorder obtained significant benefit from the JobKeeper payment on their level of coping, compared to those who did not receive JobKeeper. In contrast, receipt of the Coronavirus Supplement was not significantly associated with higher level of coping. Among those with no mental health disorder, neither the Coronavirus Supplement nor JobKeeper had a statistically significant impact on level of coping. These findings suggest the positive impacts of cash transfers on level of coping during the pandemic were limited to those with a pre-existing mental disorder who received JobKeeper.

Abstract This study was designed to assess how different prompt engineering techniques, specifically direct prompts, Chain of Thought (CoT), and a modified CoT approach, influence the ability of GPT-3.5 to answer clinical and calculation-based medical questions, particularly those styled like the USMLE Step 1 exams. To achieve this, we analyzed the responses of GPT-3.5 to two distinct sets of questions: a batch of 1000 questions generated by GPT-4, and another set comprising 95 real USMLE Step 1 questions. These questions spanned a range of medical calculations and clinical scenarios across various fields and difficulty levels. Our analysis revealed that there were no significant differences in the accuracy of GPT-3.5's responses when using direct prompts, CoT, or modified CoT methods. For instance, in the USMLE sample, the success rates were 61.7% for direct prompts, 62.8% for CoT, and 57.4% for modified CoT, with a p-value of 0.734. Similar trends were observed in the responses to GPT-4 generated questions, both clinical and calculation-based, with p-values above 0.05 indicating no significant difference between the prompt types. The conclusion drawn from this study is that the use of CoT prompt engineering does not significantly alter GPT-3.5's effectiveness in handling medical calculations or clinical scenario questions styled like those in USMLE exams. This finding is crucial as it suggests that performance of ChatGPT remains consistent regardless of whether a CoT technique is used instead of direct prompts. This consistency could be instrumental in simplifying the integration of AI tools like ChatGPT into medical education, enabling healthcare professionals to utilize these tools with ease, without the necessity for complex prompt engineering.

Abstract Virtual reality (VR) is increasingly used in the study and treatment of paranoia. This is based on the finding that people who mistakenly perceive hostile intent from other people also perceive similar threat from virtual characters. However, there has been no study of the programming characteristics of virtual characters that may influence their interpretation. We set out to investigate how the animation and expressions of virtual humans may affect paranoia. In a two-by-two factor, between-groups, randomized design, 122 individuals with elevated paranoia rated their perceptions of virtual humans, set in an eye-tracking enabled VR lift scenario, that varied in facial animation (static or animated) and expression (neutral or positive). Both facial animation (group difference = 102.328 [51.783, 152.872], p

Abstract In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch’s Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.

Abstract Enteric viral pathogens are associated with a significant burden of childhood morbidity and mortality. We investigated the relationship between viral pathogens and child growth among under-5 children. We analyzed data from 5572/22,567 children enrolled in the Global Enteric Multicenter Study across seven study sites (2007–2011). Multiple linear regression was used to examine the association between the viral pathogens and changes of length/height-for-age (HAZ), weight-for-age (WAZ), and weight-for-length/height (WHZ) z-scores, stratified by diarrheal symptoms and adjusted for potential covariates. Rotavirus (18.51%) and norovirus (7.33%) were the most prevalent enteric viral pathogens among symptomatic and asymptomatic under-5 children, respectively. Infection with individual enteric viral pathogens hurts child growth in asymptomatic children. However, the relationship with HAZ was less clear and statistically non-significant. On the other hand, the combined viral pathogens demonstrated a strong negative influence on child growth [WAZ: β coef.: − 0.10 (95%, CI − 0.15, − 0.05); P

This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p

Abstract We set out to test whether positive non-verbal behaviours of a virtual coach can enhance people's engagement in automated virtual reality therapy. 120 individuals scoring highly for fear of heights participated. In a two-by-two factor, between-groups, randomised design, participants met a virtual coach that varied in warmth of facial expression (with/without) and affirmative nods (with/without). The virtual coach provided a consultation about treating fear of heights. Participants rated the therapeutic alliance, treatment credibility, and treatment expectancy. Both warm facial expressions (group difference = 7.44 [3.25, 11.62], p = 0.001, $${eta}_{p}^{2}$$ eta p 2 =0.10) and affirmative nods (group difference = 4.36 [0.21, 8.58], p = 0.040, $${eta}_{p}^{2}$$ eta p 2 = 0.04) by the virtual coach independently increased therapeutic alliance. Affirmative nods increased the treatment credibility (group difference = 1.76 [0.34, 3.11], p = 0.015, $${eta}_{p}^{2}$$ eta p 2 = 0.05) and expectancy (group difference = 2.28 [0.45, 4.12], p = 0.015, $${eta}_{p}^{2}$$ eta p 2 = 0.05) but warm facial expressions did not increase treatment credibility (group difference = 0.64 [− 0.75, 2.02], p = 0.363, $${eta}_{p}^{2}$$ eta p 2 = 0.01) or expectancy (group difference = 0.36 [− 1.48, 2.20], p = 0.700, $${eta}_{p}^{2}$$ eta p 2 = 0.001). There were no significant interactions between head nods and facial expressions in the occurrence of therapeutic alliance (p = 0.403, $${eta}_{p}^{2}$$ eta p 2 = 0.01), credibility (p = 0.072, $${eta}_{p}^{2}$$ eta p 2 = 0.03), or expectancy (p = 0.275, $${eta}_{p}^{2}$$ eta p 2 = 0.01). Our results demonstrate that in the development of automated VR therapies there is likely to be therapeutic value in detailed consideration of the animations of virtual coaches.

Abstract Accelerated progression of chronic obstructive pulmonary disease (COPD) is associated with increased risks of hospitalization and death. Prognostic insights into mechanisms and markers of progression could facilitate development of disease-modifying therapies. Although individual biomarkers exhibit some predictive value, performance is modest and their univariate nature limits network-level insights. To overcome these limitations and gain insights into early pathways associated with rapid progression, we measured 1305 peripheral blood and 48 bronchoalveolar lavage proteins in individuals with COPD [n = 45, mean initial forced expiratory volume in one second (FEV1) 75.6 ± 17.4% predicted]. We applied a data-driven analysis pipeline, which enabled identification of protein signatures that predicted individuals at-risk for accelerated lung function decline (FEV1 decline ≥ 70 mL/year) ~ 6 years later, with high accuracy. Progression signatures suggested that early dysregulation in elements of the complement cascade is associated with accelerated decline. Our results propose potential biomarkers and early aberrant signaling mechanisms driving rapid progression in COPD.

Contemporary theory that emphasizes the roles of oxytocin and vasopressin in mammalian sociality has been shaped by seminal vole research that revealed interspecific variation in neuroendocrine circuitry by mating system. However, substantial challenges exist in interpreting and translating these rodent findings to other mammalian groups, including humans, making research on nonhuman primates crucial. Both monogamous and non-monogamous species exist within Eulemur, a genus of strepsirrhine primate, offering a rare opportunity to broaden a comparative perspective on oxytocin and vasopressin neurocircuitry with increased evolutionary relevance to humans. We performed oxytocin and arginine vasopressin 1a receptor autoradiography on 12 Eulemur brains from seven closely related species to (1) characterize receptor distributions across the genus, and (2) examine differences between monogamous and non-monogamous species in regions part of putative "pair-bonding circuits". We find some binding patterns across Eulemur reminiscent of olfactory-guided rodents, but others congruent with more visually oriented anthropoids, consistent with lemurs occupying an 'intermediary' evolutionary niche between haplorhine primates and other mammalian groups. We find little evidence of a "pair-bonding circuit" in Eulemur akin to those proposed in previous rodent or primate research. Mapping neuropeptide receptors in these nontraditional species questions existing assumptions and informs proposed evolutionary explanations about the biological bases of monogamy.

Comparing automated retinal layer segmentation using proprietary software (Heidelberg Spectralis HRA + OCT) and cross-platform Optical Coherence Tomography (OCT) segmentation software (Orion). Image segmentations of normal and diseased (iAMD, DME) eyes were performed using both softwares and then compared to the 'gold standard' of manual segmentation. A qualitative assessment and quantitative (layer volume) comparison of segmentations were performed. Segmented images from the two softwares were graded by two masked graders and in cases with difference, a senior retina specialist made a final independent decisive grading. Cross-platform software was significantly better than the proprietary software in the segmentation of NFL and INL layers in Normal eyes. It generated significantly better segmentation only for NFL in iAMD and for INL and OPL layers in DME eyes. In normal eyes, all retinal layer volumes calculated by the two softwares were moderate-strongly correlated except OUTLY. In iAMD eyes, GCIPL, INL, ONL, INLY, TRV layer volumes were moderate-strongly correlated between softwares. In eyes with DME, all layer volume values were moderate-strongly correlated between softwares. Cross-platform software can be used reliably in research settings to study the retinal layers as it compares well against manual segmentation and the commonly used proprietary software for both normal and diseased eyes.

Abstract This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p

Abstract Invasion dynamics are determined, among other aspects, by the spatial behaviour of invasive populations. The invasive toad Duttaphrynus melanostictus is spreading inland from the eastern coast of Madagascar, causing considerable ecological impacts. Understanding the basic factors determining the spread dynamics can inform management strategies and provide insights into spatial evolutionary processes. We radio-tracked 91 adult toads in three localities along the invasion gradient to determine whether spatial sorting of dispersive phenotypes is occurring, and investigate intrinsic and extrinsic determinants of spatial behaviour. Overall, toads in our study appeared as habitat generalists, and their sheltering behaviour was tied to water proximity, with toads changing shelter more frequently closer to waterbodies. Toads showed low displacement rates (mean = 4.12 m/day) and quite a philopatric behaviour but were able to perform daily movements of over 50 m. We did not detect any spatial sorting of dispersal-relevant traits nor sex- or size-biased dispersal. Our results suggest that toads are more likely to expand their range during the wet season, and that the range expansion is probably dominated by short-distance dispersal at this stage of the invasion, although a future increase in invasion speed is expected, due to the capacity for long-distance movements of this species.

Abstract Contact and projection electron radiography of static targets was demonstrated using a laser–plasma accelerator driven by a kilojoule, picosecond-class laser as a source of relativistic electrons with an average energy of 20 MeV. Objects with areal densities as high as 7.7 g/cm2 were probed in materials ranging from plastic to tungsten, and radiographs with resolution as good as 90 μm were produced. The effects of electric fields produced by the laser ablation of the radiography objects were observed and are well described by an analytic expression relating imaging magnification change to electric-field strength.

Abstract Auroral zones are regions where, in an average sense, aurorae due to solar activity are most likely spotted. Their shape and, similarly, the geographical locations most vulnerable to extreme space weather events (which we term ‘danger zones’) are modulated by Earth’s time-dependent internal magnetic field whose structure changes on yearly to decadal timescales. Strategies for mitigating ground-based space weather impacts over the next few decades can benefit from accurate forecasts of this evolution. Existing auroral zone forecasts use simplified assumptions of geomagnetic field variations. By harnessing the capability of modern geomagnetic field forecasts based on the dynamics of Earth’s core we estimate the evolution of the auroral zones and of the danger zones over the next 50 years. Our results predict that space-weather related risk will not change significantly in Europe, Australia and New Zealand. Mid-to-high latitude cities such as Edinburgh, Copenhagen and Dunedin will remain in high-risk regions. However, northward change of the auroral and danger zones over North America will likely cause urban centres such as Edmonton and Labrador City to be exposed by 2070 to the potential impact of severe solar activity.

Abstract Pre-eclampsia is associated with postnatal cardiac dysfunction; however, the nature of this relationship remains uncertain. This multicentre retrospective cohort study aimed to determine the prevalence of pre-eclampsia in women with pre-existing cardiac dysfunction (left ventricular ejection fraction

Social cognition is facilitated by oxytocin receptors (OXTR) in the hippocampus, a brain region that changes dynamically with pregnancy, parturition, and parenting experience. We investigated the impact of parenthood on hippocampal OXTR in male and female titi monkeys, a pair-bonding primate species that exhibits biparental care of offspring. We hypothesized that in postmortem brain tissue, OXTR binding in the hippocampal formation would differ between parents and non-parents, and that OXTR density would correlate with frequencies of observed parenting and affiliative behaviors between partners. Subjects were 10 adult titi monkeys. OXTR binding in the hippocampus (CA1, CA2/3, CA4, dentate gyrus, subiculum) and presubiculum layers (PSB1, PSB3) was determined using receptor autoradiography. The average frequency of partner affiliation (Proximity, Contact, and Tail Twining) and infant carrying were determined from longitudinal observations (5-6 per day). Analyses showed that parents exhibited higher OXTR binding than non-parents in PSB1 (t(8) = - 2.33, p = 0.048), and that OXTR binding in the total presubiculm correlated negatively with Proximity (r = - 0.88) and Contact (r = - 0.91), but not Tail Twining or infant carrying. These results suggest that OXTR binding in the presubiculum supports pair bonding and parenting behavior, potentially by mediating changes in hippocampal plasticity.

Levels of iron and iron-related proteins including ferritin are higher in the lung tissue and lavage fluid of individuals with chronic obstructive pulmonary disease (COPD), when compared to healthy controls. Whether more iron in the extracellular milieu of the lung associates with distinct clinical phenotypes of COPD, including increased exacerbation susceptibility, is unknown. We measured iron and ferritin levels in the bronchoalveolar lavage fluid (BALF) of participants enrolled in the SubPopulations and InteRmediate Outcome Measures In COPD (SPIROMICS) bronchoscopy sub-study (n = 195). BALF Iron parameters were compared to systemic markers of iron availability and tested for association with FEV1 % predicted and exacerbation frequency. Exacerbations were modelled using a zero-inflated negative binomial model using age, sex, smoking, and FEV1 % predicted as clinical covariates. BALF iron and ferritin were higher in participants with COPD and in smokers without COPD when compared to non-smoker control participants but did not correlate with systemic iron markers. BALF ferritin and iron were elevated in participants who had COPD exacerbations, with a 2-fold increase in BALF ferritin and iron conveying a 24% and 2-fold increase in exacerbation risk, respectively. Similar associations were not observed with plasma ferritin. Increased airway iron levels may be representative of a distinct pathobiological phenomenon that results in more frequent COPD exacerbation events, contributing to disease progression in these individuals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-β treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid β-oxidation. TGF-β treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-β-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-β treatment.

Abstract Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein–protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet’s role in some forms of DCM.

Abstract The complexities of trophic dynamics complicate the management of predator populations. Targeted culling campaigns are one management strategy meant to control predation for the benefit of the prey population. In these campaigns, individual predators are often considered “rogue” based on visitation rates to the site of concern. This definition assumes that all predators impact prey equally. However, individual variability in foraging success may compromise this assumption. To examine this hypothesis, we studied harbor seals preying on adult salmonids during the 2014–2019 fall runs in Whatcom Creek, Bellingham, Washington, USA, and recorded visitation rate and foraging success of individual seals from photographs and field observations. We then used Generalized Linear Mixed-Effects Models to model individual foraging success. Models including harbor seal identity better explained foraging success than models based on visitation rate alone. We concluded that considering intraspecific variability and classifying “rogue individuals” based on foraging success is a more accurate protocol for managing predator populations than relying solely on visitation rate of the predators.

Abstract Childhood maltreatment (CM) has been associated with adverse psychosocial outcomes during the pandemic, but the underlying mechanisms are unclear. In a prospective online study using baseline and 10-week follow-up data of 391 German participants, we applied multiple mediation analyses to test to what extent COVID-19 perceived stressors mediate the association between CM and later adverse psychosocial outcomes compared to established mediators of rumination and insecure attachment. We also explored the relative importance of different COVID-19 related stressors in predicting adverse psychological trajectories using elastic net regression. Results showed that CM was longitudinally associated with all adverse psychosocial outcome. COVID-19 perceived stressors, rumination, and insecure attachment mediated this relationship and full mediation was observed for the outcomes anxiety, stress and psychological well-being. COVID-19-related concerns about the future was most strongly and consistently associated with adverse psychosocial functioning. These findings provide preliminary evidence that COVID-19 perceived stressors, in particular concerns about the future, may be a key mechanism underlying the development of adverse psychosocial outcomes in individuals with a CM history. Thus, COVID-19 perceived stressors may require a higher priority for prevention and treatment efforts in vulnerable groups. Our results warrant replication in more representative cross-cultural samples.

Abstract Neurons in primary visual cortex are selective for stimulus orientation, and a neuron’s preferred orientation changes little when the stimulus is switched from one eye to the other. It has recently been shown that monocular orientation preferences are uncorrelated before eye opening; how, then, do they become aligned during visual experience? We aimed to provide a model for this acquired congruence. Our model, which simulates the cat’s visual system, comprises multiple on-centre and off-centre channels from both eyes converging onto neurons in primary visual cortex; development proceeds in two phases via Hebbian plasticity in the geniculocortical synapse. First, cortical drive comes from waves of activity drifting across each retina. The result is orientation tuning that differs between the two eyes. The second phase begins with eye opening: at each visual field location, on-centre cortical inputs from one eye can cancel off-centre inputs from the other eye. Synaptic plasticity reduces the destructive interference by up-regulating inputs from one eye at the expense of its fellow, resulting in binocular congruence of orientation tuning. We also show that orthogonal orientation preferences at the end of the first phase result in ocular dominance, suggesting that ocular dominance is a by-product of binocular congruence.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.

Abstract The ongoing COVID-19 global pandemic has necessitated evaluating various disinfection technologies for reducing viral transmission in public settings. Ultraviolet (UV) radiation can inactivate pathogens and viruses but more insight is needed into the performance of different UV wavelengths and their applications. We observed greater than a 3-log reduction of SARS-CoV-2 infectivity with a dose of 12.5 mJ/cm2 of 254 nm UV light when the viruses were suspended in PBS, while a dose of 25 mJ/cm2 was necessary to achieve a similar reduction when they were in an EMEM culture medium containing 2%(v/v) FBS, highlighting the critical effect of media in which the virus is suspended, given that SARS-CoV-2 is always aerosolized when airborne or deposited on a surface. It was found that SARS-CoV-2 susceptibility (a measure of the effectiveness of the UV light) in a buffer such as PBS was 4.4-fold greater than that in a cell culture medium. Furthermore, we discovered the attenuation of UVC disinfection by amino acids, vitamins, and niacinamide, highlighting the importance of determining UVC dosages under a condition close to aerosols that wrap the viruses. We developed a disinfection model to determine the effect of the environment on UVC effectiveness with three different wavelengths, 222 nm, 254 nm, and 265 nm. An inverse correlation between the liquid absorbance and the viral susceptibility was observed. We found that 222 nm light was most effective at reducing viral infectivity in low absorbing liquids such as PBS, whereas 265 nm light was most effective in high absorbing liquids such as cell culture medium. Viral susceptibility was further decreased in N95 masks with 222 nm light being the most effective. The safety of 222 nm was also studied. We detected changes to the mechanical properties of the stratum corneum of human skins when the 222 nm accumulative exposure exceeded 50 J/cm2.The findings highlight the need to evaluate each UV for a given application, as well as limiting the dose to the lowest dose necessary to avoid unnecessary exposure to the public.

Abstract Adaptive and bioinspired droplet-based materials are built using the droplet interface bilayer (DIB) technique, assembling networks of lipid membranes through adhered microdroplets. The properties of these lipid membranes are linked to the properties of the droplets forming the interface. Consequently, rearranging the relative positions of the droplets within the network will also alter the properties of the lipid membranes formed between them, modifying the transmembrane exchanges between neighboring compartments. In this work, we achieved this through the use of magnetic fluids or ferrofluids selectively dispersed within the droplet-phase of DIB structures. First, the ferrofluid DIB properties are optimized for reconfiguration using a coupled experimental-computational approach, exploring the ideal parameters for droplet manipulation through magnetic fields. Next, these findings are applied towards larger, magnetically-heterogeneous collections of DIBs to investigate magnetically-driven reconfiguration events. Activating electromagnets bordering the DIB networks generates rearrangement events by separating and reforming the interfacial membranes bordering the dispersed magnetic compartments. These findings enable the production of dynamic droplet networks capable of modifying their underlying membranous architecture through magnetic forces.

Abstract The proportion of the population who experience persecutory thoughts is 10–15%. People then engage in safety-seeking behaviours, typically avoiding social interactions, which prevents disconfirmatory experiences and hence paranoia persists. Here we show that persecutory thoughts can be reduced if prior to engaging in social interaction in VR participants first see their virtual body-double doing so. Thirty non-clinical participants were recruited to take part in a study, where they were embodied in a virtual body that closely resembled themselves, and asked to interact with members of a crowd. In the Random condition (n = 15) they observed their body-double wandering around but not engaging with the crowd. In the Targeted condition the body-double correctly interacted with members of the crowd. The Green Paranoid Thoughts Scale was measured 1 week before and 1 week after the exposure and decreased only for those in the Targeted condition. The results suggest that the observation of the body-double correctly carrying out a social interaction task in VR may lead to anxiety-reducing mental rehearsal for interaction thus overcoming safety behaviours. The results also extend knowledge of the effects of vicarious agency, suggesting that identification with the actions of body-double can influence subsequent psychological state.

Abstract Comparing automated retinal layer segmentation using proprietary software (Heidelberg Spectralis HRA + OCT) and cross-platform Optical Coherence Tomography (OCT) segmentation software (Orion). Image segmentations of normal and diseased (iAMD, DME) eyes were performed using both softwares and then compared to the ‘gold standard’ of manual segmentation. A qualitative assessment and quantitative (layer volume) comparison of segmentations were performed. Segmented images from the two softwares were graded by two masked graders and in cases with difference, a senior retina specialist made a final independent decisive grading. Cross-platform software was significantly better than the proprietary software in the segmentation of NFL and INL layers in Normal eyes. It generated significantly better segmentation only for NFL in iAMD and for INL and OPL layers in DME eyes. In normal eyes, all retinal layer volumes calculated by the two softwares were moderate-strongly correlated except OUTLY. In iAMD eyes, GCIPL, INL, ONL, INLY, TRV layer volumes were moderate-strongly correlated between softwares. In eyes with DME, all layer volume values were moderate-strongly correlated between softwares. Cross-platform software can be used reliably in research settings to study the retinal layers as it compares well against manual segmentation and the commonly used proprietary software for both normal and diseased eyes.

Abstract Challenge and threat models predict that once individuals become engaged with performance, their evaluations and cardiovascular response determine further outcomes. Although the role of challenge and threat in predicting performance has been extensively tested, few studies have focused on task engagement. We aimed to investigate task engagement in performance at the psychological and physiological levels. We accounted for physiological task engagement by examining blunted cardiovascular reactivity, the third possible cardiovascular response to performance, in addition to the challenge/threat responses. We expected that low psychological task engagement would be related to blunted cardiovascular reactivity during the performance. Gamers (N = 241) completed five matches of the soccer video game FIFA 19. We recorded psychological task engagement, heart rate reactivity, and the difference between goals scored and conceded. Lower psychological task engagement was related to blunted heart rate reactivity during the performance. Furthermore, poorer performance in the previous game was related to increased task engagement in the subsequent match. The findings extend existing literature by providing initial evidence that blunted cardiovascular reactivity may serve as the index of low task engagement.

Abstract Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of β-muricholic acid and tauro-β-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.

Abstract Dilated cardiomyopathy (DCM) is a disease of the heart muscle that affects both humans and dogs. Certain canine diets have been associated with DCM, but the diet-disease link is unexplained, and novel methods are needed to elucidate mechanisms. We conducted metabolomic profiling of 9 diets associated with canine DCM, containing ≥ 3 pulses, potatoes, or sweet potatoes as main ingredients, and in the top 16 dog diet brands most frequently associated with canine DCM cases reported to the FDA (3P/FDA diets), and 9 non-3P/FDA diets. We identified 88 named biochemical compounds that were higher in 3P/FDA diets and 23 named compounds that were lower in 3P/FDA diets. Amino acids, amino acid-derived compounds, and xenobiotics/plant compounds were the largest categories of biochemicals that were higher in 3P/FDA diets. Random forest analyses identified the top 30 compounds that distinguished the two diet groups with 100% predictive accuracy. Four diet ingredients distinguished the two diet groups (peas, lentils, chicken/turkey, and rice). Of these ingredients, peas showed the greatest association with higher concentrations of compounds in 3P/FDA diets. Moreover, the current foodomics analyses highlight relationships between diet and DCM in dogs that can identify possible etiologies for understanding diet-disease relationships in dogs and humans.

Abstract Medical cannabis (MC) production is a rapidly expanding industry. Over the past ten years, many additional phytocannabinoids have been discovered and used for different purposes. MC was reported beneficial for the treatment of a variety of clinical conditions such as analgesia, multiple sclerosis, spinal cord injuries, Tourette's syndrome, epilepsy, glaucoma, Parkinson disease and more. Yet, there is still a major lack of research and knowledge related to MC plant diseases, both at the pre- and postharvest stages. Many of the fungi that infect MC, such as Aspergillus and Penicillium spp., are capable of producing mycotoxins that are carcinogenic, or otherwise harmful when consumed, and especially by those patients who suffer from a weakened immune system, causing invasive contamination in humans. Therefore, there are strict limits regarding the permitted levels of fungal colony forming units (CFU) in commercial MC inflorescences. Furthermore, the strict regulation on pesticide appliance application in MC cultivation exacerbates the problem. In order to meet the permitted CFU limit levels, there is a need for pesticide-free postharvest treatments relying on natural non-chemical methods. Thus, a decontamination approach is required that will not damage or significantly alter the chemical composition of the plant product. In this research, a new method for sterilization of MC inflorescences for reduction of fungal contaminantstes was assessed, without affecting the composition of plant secondary metabolites. Inflorescences were exposed to short pulses of steam (10, 15 and 20 s exposure) and CFU levels and plant chemical compositions, pre- and post-treatment, were evaluated. Steam treatments were very effective in reducing fungal colonization to below detection limits. The effect of these treatments on terpene profiles was minor, resulting mainly in the detection of certain terpenes that were not present in the untreated control. Steaming decreased cannabinoid concentrations as the treatment prolonged, although insignificantly. These results indicate that the steam sterilization method at the tested exposure periods was very effective in reducing CFU levels while preserving the initial molecular biochemical composition of the treated inflorescences.