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Inspired by recent human studies, this paper investigates the benefits of employing varying navigation strategies in robot teams. We explore how mixed navigation strategies impact task completion time, environment exploration, and overall system effectiveness in multi-robot systems. Experiments were conducted in a simulated rectangular environment using Clearpath PR2 robots and evaluated different navigation strategies observed in humans: 1) Route (RT) knowledge where agents follow a predefined path, 2) Survey (SW) knowledge where agents take the shortest path while avoiding obstacles, 3) Mixed strategies with varying proportions, such as 40% RT and 60% SW (0.4RT 0.6SW) and 60% RT and 40% SW (0.6RT 0.4SW), and 4) An additional strategy where agents switch from RT to SW 10% of the time (0.9RT 0.1SW). While SW strategy is the most time-efficient, RT strategy covers more of the environment. Mixed strategies offer a balanced trade-off. These findings highlight the advantages of variability in navigation strategies, suggesting benefits in both biological and robotic populations. Additionally, we have observed that human participants in a similar study would start on a route, and then 10% of the time switch to survey. Therefore, we investigate a 90% Route 10% Survey (0.9RT 0.1SW) strategy for individual team members. While a pure Survey strategy is the most efficient regarding time taken and a pure Route strategy covers more of the environment, a mixture of strategies appears to be a beneficial tradeoff between time taken to complete a mission and area coverage. These results highlight the advantages of population variability, suggesting potential benefits in both biological and robotic populations.

Abstract Objectives To assess the effect of bilateral orchidopexy in preventing future torsion and testicular loss in patients with intermittent testicular torsion. Secondarily, this study aims to assess the rate of pain improvement following orchidopexy. Methods This is a prospective cohort of patients. Participants were men who underwent elective bilateral orchidopexy for intermittent testicular torsion. All consecutive cases were treated by a single surgeon in a single centre between 2015 and 2023. The primary outcomes were prevention of torsion and testicular loss. The secondary outcome was the resolution or improvement in pain. Results The success rate of bilateral orchidopexy in preventing testicular loss due to torsion was 100%, at a follow‐up of mean 33.5 months. Of the 50 patients, 88% were pain‐free following orchidopexy, and 12% had an improvement in their pain. There were no cases of hydrocoele or haematoma in this series. To our knowledge, this is the largest series reported in the literature. Conclusions Elective bilateral orchidopexy prevents torsion and preserves testicular viability. Pain is resolved in most but not all cases. This is important in counselling men who are considering surgical management of intermittent torsion of the testicle.

There are known individual differences in both the ability to learn the layout of novel environments and the flexibility of strategies for navigating known environments. However, it is unclear how navigational abilities are impacted by high-stress scenarios. Here we used immersive virtual reality (VR) to develop a novel behavioral paradigm to examine navigation under dynamically changing situations. We recruited 48 participants (24 female; ages 17-32) to navigate a virtual maze (7.5 m × 7.5 m). Participants learned the maze by moving along a fixed path past the mazes landmarks (paintings). Subsequently, participants experienced either a non-stress condition, or a high-stress condition tasking them with navigating the maze. In the high-stress condition, their initial path was blocked, the environment was darkened, threatening music was played, fog obstructed more distal views of the environment, and participants were given a time limit of 20 s with a countdown timer displayed at the top of their screen. On trials where the path was blocked, we found self-reported stress levels and distance traveled increased while trial completion rate decreased (as compared to non-stressed control trials). On unblocked stress trials, participants were less likely to take a shortcut and consequently navigated less efficiently compared to control trials. Participants with more trait spatial anxiety reported more stress and navigated less efficiently. Overall, our results suggest that navigational abilities change considerably under high-stress conditions.

Abstract Background The World Professional Association for Transgender Health guidelines Standards of Care 8 draw on ethical arguments based on individual autonomy, to argue that healthcare and other professionals should be advocates for trans people. Such guidelines presume the presence of medical services for trans people and a degree of consensus on medical ethics. Very little is known, however, about the ethical challenges associated with both providing and accessing trans healthcare, including gender affirmation, in the Global South. In light of the challenges associated with medical and legal gender affirmation in Indonesia, we conducted a qualitative study to understand the views of trans people, healthcare providers, and legal practitioners. Methods In this qualitative study, we drew on a participatory methodology to conduct 46 semi-structured interviews between October and December 2023, with trans people (10 trans feminine people and 10 trans masculine people, each interviewed twice) and key informants (three healthcare providers and three lawyers and paralegals). Trans people were a central part of the research team from inception through to analysis and writing. Participants were recruited via community-led sampling. Data analysis of interview data took place through an immersion/crystallisation technique and preliminary inductive coding which highlighted key quotes. We focused on an inductive analysis using participant narratives to identify key concepts in the ethics of gender affirmation in Indonesia. Results We characterize the ethics of supportive healthcare workers, community members, and family members, as that akin to “accomplices,” a concept of ethics used in theories of racial justice which evaluate a willingness to support people to navigate laws and regulations which perpetuate injustices and violence. Overall, both trans people and key informants shared an understanding that the legal status of gender-affirming medical care was particularly ambiguous in Indonesia due to a lack of clarity in both laws and regulations. For trans participants, ethical arguments for the validity of legal and medical gender affirmation was premised on evidence that their gender identity and expression was already recognized within society, even if limited to immediate friends and family. Given that all participants expressed a desire for gender affirmation, but such services were widely unavailable, accomplices played a crucial role in supporting trans people to access healthcare. Conclusions An empirical study based on an “ethics from below” helps to show that arguments grounded in autonomy, or based on biomedical evidence, are unlikely to alter unjust laws or facilitate a change to pathologizing guidelines governing understanding of trans people’s healthcare and legal needs in Indonesia. We provide an analysis that is sensitive to the ethics of facilitating gender affirmation in a context where that process is inherently social, and often articulated in relation to a prevailing religious morality.

Abstract Developmental toxicity (DevTox) tests evaluate the adverse effects of chemical exposures on an organism’s development. Although current testing primarily relies on large mammalian models, the emergence of new approach methodologies (NAMs) is encouraging industries and regulatory agencies to evaluate novel assays. C. elegans have emerged as NAMs for rapid toxicity testing because of its biological relevance and suitability to high throughput studies. However, current low-resolution and labor-intensive methodologies prohibit its application for sub-lethal DevTox studies at high throughputs. With the recent advent of the large-scale microfluidic device, vivoChip, we can now rapidly collect 3D high-resolution images of ~ 1000 C. elegans from 24 different populations. While data collection is rapid, analyzing thousands of images remains time-consuming. To address this challenge, we developed a machine-learning (ML)-based image analysis platform using a 2.5D U-Net architecture (vivoBodySeg) that accurately segments C. elegans in images obtained from vivoChip devices, achieving a Dice score of 97.80%. vivoBodySeg processes 36 GB data per device, phenotyping multiple body parameters within 35 min on a desktop PC. This analysis is ~ 140 × faster than the manual analysis. This ML approach delivers highly reproducible DevTox parameters (4–8% CV) to assess the toxicity of chemicals with high statistical power.

Spatial thinking skills are associated with performance, persistence, and achievement in science, technology, engineering, and mathematics (STEM) school subjects. Because STEM knowledge and skills are integral to developing a well-trained workforce within and beyond STEM, spatial skills have become a major focus of cognitive, developmental, and educational research. However, these efforts are greatly hampered by the current lack of access to reliable, valid, and well-normed spatial tests. Although there are hundreds of spatial tests, they are often hard to access and use, and information about their psychometric properties is frequently lacking. Additional problems include (1) substantial disagreement about what different spatial tests measure-even two tests with similar names may measure very different constructs; (2) the inability to measure some STEM-relevant spatial skills by any existing tests; and (3) many tests only being available for specific age groups. The first part of this report delineates these problems, as documented in a series of structured and open-ended interviews and surveys with colleagues. The second part outlines a roadmap for addressing the problems. We present possibilities for developing shared testing systems that would allow researchers to test many participants through the internet. We discuss technological innovations, such as virtual reality, which could facilitate the testing of navigation and other spatial skills. Developing a bank of testing resources will empower researchers and educators to explore and support spatial thinking in their disciplines, as well as drive the development of a comprehensive and coherent theoretical understanding of spatial thinking.

IntroductionDespite its importance for navigation, very little is known about how the normal aging process affects spatial exploration behavior. We aimed to investigate: (1) how spatial exploration behavior may be altered early in the aging process, (2) the relationship between exploration behavior and subsequent spatial memory, and (3) whether exploration behavior can classify participants according to age.MethodsFifty healthy young (aged 18-28) and 87 healthy midlife adults (aged 43-61) freely explored a desktop virtual maze, learning the locations of nine target objects. Various exploration behaviors (object visits, distance traveled, turns made, etc.) were measured. In the test phase, participants navigated from one target object to another without feedback, and their wayfinding success (% correct trials) was measured.ResultsIn the exploration phase, midlife adults exhibited less exploration overall compared to young adults, and prioritized learning target object locations over maze layout. In the test phase, midlife adults exhibited less wayfinding success when compared to the young adults. Furthermore, following principal components analysis (PCA), regression analyses indicated that both exploration quantity and quality components were associated with wayfinding success in the midlife group, but not the young adults. Finally, we could classify participants according to age with similar accuracy using either their exploration behavior or wayfinding success scores.DiscussionOur results aid in the understanding of how aging impacts spatial exploration, and encourages future investigations into how pathological aging may affect spatial exploration behavior.

Abstract Background Exposure to domestic and family violence is a pervasive form of complex trauma and a major global public health problem. At the frontline of the health system, primary healthcare practitioners are uniquely placed to support individuals with experiences of trauma, yet their views on trauma-informed primary care are not well understood. This systematic review of qualitative literature sought to explore primary healthcare practitioners’ perspectives on trauma-informed primary care. Methods Eight databases were searched up to July 2023. Studies were included if they consisted of empirical qualitative data, were conducted in general practice or equivalent generalist primary healthcare settings, and included the perspectives of primary healthcare practitioners where they could be distinguished from other participants in the analysis. Thematic synthesis was used for analysis. Results 13 papers met inclusion criteria, representing primary care settings from the United States, Canada, Australia, and Norway. Three key themes were developed: Changing the paradigm, Building trust, and Navigating the emotional load. Findings shed light on how primary healthcare practitioners perceive and strive to practise trauma-informed primary healthcare and the challenges of navigating complex, trauma-related work in the primary care environment. Conclusions This review supports the need for recognition of the value of primary care in supporting patients with histories of trauma and violence, the development of interventions to mitigate the emotional load worn by primary healthcare practitioners, and further work to develop a deep and consistent understanding of what trauma-informed primary care encompasses.

People use environmental knowledge to maintain a sense of direction in daily life. This knowledge is typically measured by having people point to unseen locations (judgments of relative direction) or navigate efficiently in the environment (shortcutting). Some people can estimate directions precisely, while others point randomly. Similarly, some people take shortcuts not experienced during learning, while others mainly follow learned paths. Notably, few studies have directly tested the correlation between pointing and shortcutting performance. We compared pointing and shortcutting in two experiments, one using desktop virtual reality (VR) (N = 57) and one using immersive VR (N = 48). Participants learned a new environment by following a fixed route and were then asked to point to unseen locations and navigate to targets by the shortest path. Participants performance was clustered into two groups using K-means clustering. One (lower ability) group pointed randomly and showed low internal consistency across trials in pointing, but were able to find efficient routes, and their pointing and efficiency scores were not correlated. The others (higher ability) pointed precisely, navigated by efficient routes, and their pointing and efficiency scores were correlated. These results suggest that with the same egocentric learning experience, the correlation between pointing and shortcutting depends on participants learning ability, and internal consistency and discriminating power of the measures. Inconsistency and limited discriminating power can lead to low correlations and mask factors driving human variation. Psychometric properties, largely under-reported in spatial cognition, can advance our understanding of individual differences and cognitive processes for complex spatial tasks.

Foraging behavior requires weighing costs of time to decide when to leave one reward patch to search for another. Computational and animal studies suggest that striatal dopamine is key to this process; however, the specific role of dopamine in foraging behavior in humans is not well characterized. We use positron emission tomography (PET) imaging to directly measure dopamine synthesis capacity and D1 and D2/3 receptor availability in 57 healthy adults who complete a computerized foraging task. Using voxelwise data and principal component analysis to identify patterns of variation across PET measures, we show that striatal D1 and D2/3 receptor availability and a pattern of mesolimbic and anterior cingulate cortex dopamine function are important for adjusting the threshold for leaving a patch to explore, with specific sensitivity to changes in travel time. These findings suggest a key role for dopamine in trading reward benefits against temporal costs to modulate behavioral adaptions to changes in the reward environment critical for foraging.

KCC2 is CNS neuron-specific chloride extruder, essential for the establishment and maintenance of the transmembrane chloride gradient, thereby enabling synaptic inhibition within the CNS. Herein, we highlight KCC2 hypofunction as a fundamental and conserved pathology contributing to neuronal circuit excitation/inhibition (E/I) imbalances that underly epilepsies, chronic pain, neuro-developmental/-traumatic/-degenerative/-psychiatric disorders. Indeed, downstream of both acquired and genetic factors, multiple pathologies (e.g., hyperexcitability and inflammation) converge to impair KCC2-dependent inhibition in CNS. When KCC2 hypofunction occurs, affected neurons are disinhibited due to impaired inhibitory responses to GABA/glycine. This causes neuronal hyperexcitability, disinhibition within neuron circuits, and disrupted neurological functions. More recently, KCC2 was identified as a genetically-validated target for epilepsy, intellectual disability, and autism spectrum disorder, and pathogenic mutations in human SLC12A5 gene were linked to psychiatric/mood disorders. The broad therapeutic utility of KCC2-upmodulating drugs relates to its critical role in determining inhibitory activity of GABAergic neurotransmission, a mechanism widely targeted by several drugs. However, in cases of KCC2 hypofunction GABAergic neurotransmission can be depolarizing/excitatory, thereby impairing endogenous neuronal inhibition while also limiting the effectiveness of existing therapeutics targeting/requiring GABAergic pathway inhibition. Several preclinical reports have shown that KCC2 upmodulating treatments rescue and increase the efficacy of anti-seizure and analgesic medications. Thus, a first-in-class KCC2-potentiating therapy would provide a novel mechanism for restoring physiological CNS inhibition and addressing drug resistance in patients with E/I imbalance pathologies. Herein, we discuss progress toward and further work needed to develop the first-in-class KCC2 therapeutics to treat neurological disorder patients.

Community activists, policymakers and researchers have long identified human rights as central to addressing the HIV epidemic. Over the past 10 years, efforts to incorporate human rights into the HIV response have focused on reforming laws which criminalise sex work and male-to-male sex. Laws criminalising sex work and male-to-male sex drive communities underground, making HIV prevention, testing, and treatment efforts more difficult. This article draws on a qualitative study conducted in Papua New Guinea (PNG) which examined stakeholder views on prospects for law reform, the impact of criminal laws on communities, and the role of law reform in addressing the HIV epidemic. While efforts to reform criminal laws related to sex work and male-to-male sex have taken place in PNG, these have been unsuccessful. Stakeholders identified that strategies for addressing criminal laws and the impacts of law reform must be grounded in the PNG context, that there must be material support for community members to engage with criminal laws and human rights, and that dignity rather than HIV should be the justification for law reform.

Abstract Background The Center for Medicare and Medicaid Services (CMS) imposes payment penalties for readmissions following total joint replacement surgeries. This study focuses on total hip, knee, and shoulder arthroplasty procedures as they account for most joint replacement surgeries. Apart from being a burden to healthcare systems, readmissions are also troublesome for patients. There are several studies which only utilized structured data from Electronic Health Records (EHR) without considering any gender and payor bias adjustments. Methods For this study, dataset of 38,581 total knee, hip, and shoulder replacement surgeries performed from 2015 to 2021 at Novant Health was gathered. This data was used to train a random forest machine learning model to predict the combined endpoint of emergency department (ED) visit or unplanned readmissions within 30 days of discharge or discharge to Skilled Nursing Facility (SNF) following the surgery. 98 features of laboratory results, diagnoses, vitals, medications, and utilization history were extracted. A natural language processing (NLP) model finetuned from Clinical BERT was used to generate an NLP risk score feature for each patient based on their clinical notes. To address societal biases, a feature bias analysis was performed in conjunction with propensity score matching. A threshold optimization algorithm from the Fairlearn toolkit was used to mitigate gender and payor biases to promote fairness in predictions. Results The model achieved an Area Under the Receiver Operating characteristic Curve (AUROC) of 0.738 (95% confidence interval, 0.724 to 0.754) and an Area Under the Precision-Recall Curve (AUPRC) of 0.406 (95% confidence interval, 0.384 to 0.433). Considering an outcome prevalence of 16%, these metrics indicate the model’s ability to accurately discriminate between readmission and non-readmission cases within the context of total arthroplasty surgeries while adjusting patient scores in the model to mitigate bias based on patient gender and payor. Conclusion This work culminated in a model that identifies the most predictive and protective features associated with the combined endpoint. This model serves as a tool to empower healthcare providers to proactively intervene based on these influential factors without introducing bias towards protected patient classes, effectively mitigating the risk of negative outcomes and ultimately improving quality of care regardless of socioeconomic factors.

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset

Colonization has had extremely negative impacts on the mental health and wellness of Indigenous peoples throughout the world. In this paper we take up colonial processes as they relate to Indigenous lives and mental health in three contexts: Canada, Kenya and Australia. This work engages storytelling and the method of storywork (Archibald et al., 2019) as a way to preserve and pass on history and as a way of resisting colonial oppression. This work is grounded in an intersectional approach to social justice and decolonization (Crenshaw, 1990; Hankivsky & Cormier, 2011), and supported sharing, knowledge co-creation and joint thematic narrative analysis of Indigenous experiences of mental health and justice systems across the three contexts. Our writing team represents a collaborative process between Indigenous and non-Indigenous authors where the members of the team most impacted by colonization use stories to reflect on the impact of colonization and its specific ties to psychiatric, justice and child welfare systems. This paper is presented in three main parts beginning with “Emile’s Story,” followed by “Remembering ‘Is That You Ruthie?’” and concluding with “Navigating Kenya’s Colonial Legacy.” This work engages a process of decolonization by challenging these destructive colonial narratives through storytelling. This paper will both document and demonstrate the importance of creating space for different forms of knowledge creation within academia.

Objectives: To assess the understanding of people diagnosed with ovarian cancer regarding genetic testing; to understand knowledge gaps among people diagnosed with ovarian cancer that may impact best practice care; and to monitor overall changes in understanding from 2015 to 2022. Design: Longitudinal ’opt-in’ study using an online survey tool at three timepoints: 2015, 2018 and 2022. Participants: People in Australia (or their families / caregivers) diagnosed with ovarian cancer between 2010 and 2022). Main outcome measures: Self-reported awareness of heritable risk factors for ovarian cancer, genetic testing approaches and participation in clinical trials. Results: The study indicated that there have been improvements in the understanding and awareness of people diagnosed with ovarian cancer regarding familial risk (an increase from 43.6% (45 of 149) in 2015 to 62.9% (166 of 264) in 2022); but people were less likely to be aware of the difference between somatic (tumour) and germline testing (120 of 266, 45.1%). However, there were self-reported improvements to clinical trial access in non-metropolitan areas (12 of 64, 18.8% in 2022 compared to 22 of 145, 15.2% in 2018), bringing it on par with metropolitan areas (32 of 169, 18.9% in 2022). Conclusions: Despite improved awareness about genetic testing among people diagnosed with ovarian cancer, there remain knowledge gaps in understanding of genetic testing types (germline and somatic) and gene variant targeted therapies; and further work to improve clinical trial awareness and access is required.

BackgroundWearable physiological monitoring devices are promising tools for remote monitoring and early detection of potential health changes of interest. The widespread adoption of such an approach across communities and over long periods of time will require an automated data platform for collecting, processing, and analyzing relevant health information. ObjectiveIn this study, we explore prospective monitoring of individual health through an automated data collection, metrics extraction, and health anomaly analysis pipeline in free-living conditions over a continuous monitoring period of several months with a focus on viral respiratory infections, such as influenza or COVID-19. MethodsA total of 59 participants provided smartwatch data and health symptom and illness reports daily over an 8-month window. Physiological and activity data from photoplethysmography sensors, including high-resolution interbeat interval (IBI) and step counts, were uploaded directly from Garmin Fenix 6 smartwatches and processed automatically in the cloud using a stand-alone, open-source analytical engine. Health risk scores were computed based on a deviation in heart rate and heart rate variability metrics from each individual’s activity-matched baseline values, and scores exceeding a predefined threshold were checked for corresponding symptoms or illness reports. Conversely, reports of viral respiratory illnesses in health survey responses were also checked for corresponding changes in health risk scores to qualitatively assess the risk score as an indicator of acute respiratory health anomalies. ResultsThe median average percentage of sensor data provided per day indicating smartwatch wear compliance was 70%, and survey responses indicating health reporting compliance was 46%. A total of 29 elevated health risk scores were detected, of which 12 (41%) had concurrent survey data and indicated a health symptom or illness. A total of 21 influenza or COVID-19 illnesses were reported by study participants; 9 (43%) of these reports had concurrent smartwatch data, of which 6 (67%) had an increase in health risk score. ConclusionsWe demonstrate a protocol for data collection, extraction of heart rate and heart rate variability metrics, and prospective analysis that is compatible with near real-time health assessment using wearable sensors for continuous monitoring. The modular platform for data collection and analysis allows for a choice of different wearable sensors and algorithms. Here, we demonstrate its implementation in the collection of high-fidelity IBI data from Garmin Fenix 6 smartwatches worn by individuals in free-living conditions, and the prospective, near real-time analysis of the data, culminating in the calculation of health risk scores. To our knowledge, this study demonstrates for the first time the feasibility of measuring high-resolution heart IBI and step count using smartwatches in near real time for respiratory illness detection over a long-term monitoring period in free-living conditions.

Spatial reasoning is an inherent aspect of everyday life. For example, spatial reasoning supports young children playing with blocks, older children learning about positioning on a sports field, and adults navigating where they need to go. Spatial reasoning is also a critical aspect of STEM (science, technology, engineering, mathematics, e.g., Wai, Lubinski, & Benbow, 2009). For example, chemists imagine molecules rotating to compare structure, and physicists reason about the influence of invisible forces on magnetic fields.

Activation in brain regions associated with spatial navigation, such as the hippocampus and entorhinal cortex - a critical hub for grid cells - has also been observed during tasks such as representing a social network or abstract conceptual relations. To demonstrate a behavioral parallel between cognitive maps of abstract and physical spaces, we developed a novel task in which participants constructed spatial representations of relational statements along two dimensions, and were tested on ability to make inferences from these statements. Participants’ representations varied widely, with some using a regular, hexagonal grid pattern. The uniformity of their patterns correlated with performance on the inference task, a spatial ability measure, and a spatial habits of mind questionnaire. These findings support extant research proposing a flexible cognitive map system used for representing both physical space and conceptual relations, and suggest that this system is subject to individual differences in more general spatial processing.

The administrative documents produced in Transjordan during the first decades of the British Mandate concerning the Banu Sakhr Bedouin tribe offer a detailed case study of state-making and the consequent disruption of autonomous nomadic pastoralist society. In the late Ottoman period, the tribe remained largely self-sufficient and beyond the reach of the authorities by virtue of their flocks of camels. But the extension of state-making into the desert regions during the Mandate, associated above all with the activities of one British army officer, John Bagot Glubb, served to undermine Banu Sakhr camel husbandry and alter the power dynamics between tribe and state. Taxation, control of mobility, border regimes and an end to inter-tribal raiding, combined with drought and economic depression, forced the tribe to diversify away from camel pastoralism. This process altered the Banu Sakhr social system and solidified the encapsulation of the tribe within the nascent state.

California has a fast-growing malting industry in need of local production of malting barley (Hordeum vulgare L.) to provide malt to a well-established craft brewing industry. ‘UC-Capay’ (Reg. no. CV-376, PI 698168, PVP application number 202100205) is the third malting barley cultivar released by the University of California, following ‘UC Tahoe’ (2016) and ‘Butta 12’ (2019). UC-Capay is an early-flowering, two-rowed spring malting barley with low grain protein content, characterized by its exceptional large and plump grains. UC-Capay is adapted to the California's Central Valley (Sacramento and San Joaquin Valleys) and is resistant to all common diseases present in this region. UC-Capay is a non-glycoside nitrile producer, a trait highly valued by craft maltsters and distillers. UC-Capay meets the quality standards of a craft malting and brewing industry interested in sourcing locally grown barley.

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

Science, Technology, Engineering, and Mathematics (STEM) domains require people to recognize and transform complex visuospatial displays that appear to vastly exceed the limits of visuospatial working memory. Here, we consider possible domain-general mechanisms that may explain this advantage: capitalizing on symmetry, a structural regularity that can produce more efficient representations. Participants briefly viewed a structure made up of three-dimensional connected cubes of different colors, which was either asymmetrical or symmetrical. After a short delay, they were asked to detect a change (colors swapping positions) within a rotated second view. In change trials, the second display always had an asymmetrical structure. The presence of symmetry in the initial view improved change detection, and performance also declined with angular disparity of the encoding and test displays. People with higher spatial ability performed better on the change-detection task, but there was no evidence that they were better at leveraging symmetry than low-spatial individuals. The results suggest that leveraging symmetrical structures can help people of all ability levels exceed typical working memory limits by constructing more efficient representations and substituting resource-demanding mental rotation operations with alternative orientation-independent strategies.

The question of whether SARS-CoV-2 is mainly transmitted by droplets or aerosols has been highly controversial. We sought to explain this controversy through a historical analysis of transmission research in other diseases. For most of human history, the dominant paradigm was that many diseases were carried by the air, often over long distances and in a phantasmagorical way. This miasmatic paradigm was challenged in the mid to late 19th century with the rise of germ theory, and as diseases such as cholera, puerperal fever, and malaria were found to actually transmit in other ways. Motivated by his views on the importance of contact/droplet infection, and the resistance he encountered from the remaining influence of miasma theory, prominent public health official Charles Chapin in 1910 helped initiate a successful paradigm shift, deeming airborne transmission most unlikely. This new paradigm became dominant. However, the lack of understanding of aerosols led to systematic errors in the interpretation of research evidence on transmission pathways. For the next five decades, airborne transmission was considered of negligible or minor importance for all major respiratory diseases, until a demonstration of airborne transmission of tuberculosis (which had been mistakenly thought to be transmitted by droplets) in 1962. The contact/droplet paradigm remained dominant, and only a few diseases were widely accepted as airborne before COVID-19: those that were clearly transmitted to people not in the same room. The acceleration of interdisciplinary research inspired by the COVID-19 pandemic has shown that airborne transmission is a major mode of transmission for this disease, and is likely to be significant for many respiratory infectious diseases.

Same-day emergency care (SDEC) in unplanned and emergency care is an NHS England (NHSE) priority. Optimal use of these services requires rapid identification of suitable patients. NHSE suggests the use of one tool for this purpose. This systematic review compares studies that evaluate the performance of selection tools for SDEC pathways.Nine studies met the inclusion criteria. Three scores were evaluated: the Amb score (seven studies), Glasgow Admission Prediction Score (GAPS) (six studies) and Sydney Triage to Admission Risk Tool (START) (two studies). There was heterogeneity in the populations assessed, exclusion criteria used and definitions used for SDEC suitability, with proportions of patients deemed ‘suitable’ for SDEC ranging from 20 to 80%. Reported score sensitivity and specificity ranged between 18–99% and 10–89%. Score performance could not be compared due to heterogeneity between studies. No studies assessed clinical implementation.The current evidence to support the use of a specific tool for SDEC is limited and requires further evaluation.