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Abstract The high latitude ionospheric evolution of the May 10‐11, 2024, geomagnetic storm is investigated in terms of Total Electron Content and contextualized with Incoherent Scatter Radar and ionosonde observations. Substantial plasma lifting is observed within the initial Storm Enhanced Density plume with ionospheric peak heights increasing by 150–300 km, reaching levels of up to 630 km. Scintillation is observed within the cusp during the initial expansion phase of the storm, spreading across the auroral oval thereafter. Patch transport into the polar cap produces broad regions of scintillation that are rapidly cleared from the region after a strong Interplanetary Magnetic Field reversal at 2230UT. Strong heating and composition changes result in the complete absence of the F2‐layer on the eleventh, suffocating high latitude convection from dense plasma necessary for Tongue of Ionization and patch formation, ultimately resulting in a suppression of polar cap scintillation on the eleventh.

Abstract Casitas B‐cell lineage (CBL) syndrome is a rare RASopathy known to predispose to CBL‐mutated juvenile myelomonocytic leukemia (JMML) in childhood. Adulthood acute myeloid leukemia arising out of a genetic aberrancies consistent with prior CBL‐mutated JMML has been twice previously described, but chronic myeloproliferative neoplasia has not. We present a case of progressive myeloproliferative neoplasm in adulthood in the context of CBL syndrome alongside a novel CSF3R variant. We also review pathogenic splice‐site mutations in CBL‐mutated JMML.

Abstract Objective This scoping review assesses existing research on observation units, examining diagnoses, clinical outcomes, finances, and health system comparisons to identify knowledge gaps related to patients in dedicated emergency observation units. Methods The scoping review follows the Joanna Briggs Institute (JBI) methodology and was published prior to the review on Open Science Framework. Databases searched included MEDLINE/PubMed, Embase (Ovid), and CINAHL (Ebsco), with unpublished studies and gray literature identified via Web of Science. Articles were screened and extracted by two reviewers in Covidence. Any data or inclusion criteria inconsistencies were resolved through arbitration by a third researcher or by team consensus. Data were transferred to Excel for analysis. Results A total of 1061 studies were assessed for eligibility: 461 articles met study inclusion criteria and 433 were excluded for being abstracts only. Of these 461 articles, the majority focused on cardiac diagnoses (111/461, 24%) and adult populations (321/461, 70%) and are retrospective or cohort studies (241/461, 52%). Fifty‐four articles (12%) belonged to expert opinion category. Length of stay (191/461, 41%) is the most common outcome measure followed by morbidity/mortality (189/461, 41%), admission/failure rate (169/461, 37%), and protocol assessments (120/461, 26%). Few articles focused on staff models and structure but 121 of 461 (26%) mentioned it. Note that 162 (35%) measured hospital finances, and 120 (26%) articles performed some direct comparison to other forms of observation. Conclusion While reimbursement and cardiac conditions are frequently assessed in emergency department observation unit literature, there is paucity of discussion on staffing models and other diagnoses remain less frequently explored. This review aims to spotlight future research areas in observation medicine.

Abstract Background Advancements in cancer treatment and survivorship rely on participation in research and access to health records. Methods This study explored preferences for data access and sharing in 14 workshops with 42 community members, most of whom were a cancer survivor or carer. Various scenarios for data access and sharing were presented and discussed, with participants' preferences summarized using descriptive statistics. Reasons underlying these preferences were identified through a thematic analysis of workshop transcripts. Results Most participants indicated a willingness for researchers to use their self‐report data and current health records for a specific research project (86%). Many were also willing for their self‐report data and current (62%) or all future (44%) health records to be shared with other researchers for use in other studies if made aware of this. Willingness to consent to data access and sharing data in cancer research was influenced by: (i) the potential for data sharing to advance medical discoveries and benefit people impacted by cancer in the future, (ii) transparency around researchers' credibility and their intentions for data sharing, (iii) level of ownership and control over data sharing, and (iv) protocols for privacy and confidentiality in data sharing. Conclusions Based on these themes, we present practical strategies for optimizing data access and sharing in cancer research.

Abstract Ice sheet feedbacks are underrepresented in model assessments of climate sensitivity and their magnitudes are still poorly constrained. We combine a recently published record of Earth's Energy Imbalance (EEI) with existing reconstructions of temperature, atmospheric composition, and sea level to estimate both the magnitude and timescale of the ice sheet‐albedo feedback since the Last Glacial Maximum. This facilitates the first opportunity to quantify this feedback over the most recent deglaciation using a proxy data‐driven approach. We find the ice sheet‐albedo feedback to be amplifying, increasing the total climate feedback parameter by 42% and reaching an equilibrium magnitude of 0.55 Wm−2K−1, with a 66% confidence interval of 0.45–0.63 Wm−2K−1. The timescale to equilibrium is estimated as 3.6 ka (66% confidence: 1.9–5.5 ka). These results provide new evidence for the timescale and magnitude of the amplifying ice sheet‐albedo feedback that will drive anthropogenic warming for millennia to come.

Abstract Most pollinator policy initiatives are focused on habitat restoration and increasing the availability of floral resources, yet the choice of plant species is not always compatible with farming system cultivation and management needs. In this paper, we developed a framework for selecting plants to specifically meet stakeholder needs. We trialled 19 plant species and collected observational data on plant‐insect visitors, plant survival in the orchard environment and potential risks to crops and the environment. We used this framework to identify plants suitable to incorporate into blueberry cropping systems. Practical implication: Our framework ensured plant choice based on informed decisions and allowed the selection of two plant species that aligned well with industry needs. Different plants may be optimal for different conservation aims, hence plants selected need ideally to be evaluated for their use by the flower‐visiting taxa, as well as align with industry growing practices and needs.

Background Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. Methods and Results Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre‐LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post‐LVAD follow‐up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post‐LVAD−LVEF pre‐LVAD). We quantified the association of pre‐LVAD HbA1c with ΔLVEF as the primary outcome, and all‐cause mortality and LVAD‐related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD‐related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre‐ and post‐LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre‐LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end‐diastolic diameter. Pre‐LVAD HbA1c was not associated with all‐cause mortality, but higher pre‐LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD‐related infection, and device thrombosis by 3 years on LVAD support (P

Abstract Introduction Optimizing uptake of pre‐exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. Methods In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP‐designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community‐based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme‐specific tools and the national electronic health record. We estimated the before‐after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed‐effects regression to estimate marginal probabilities of PrEP continuity. Results Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community‐based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue‐based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p

Abstract Introduction Magnetic resonance imaging (MRI) is being increasingly used to improve radiation therapy planning by allowing visualisation of organs at risk that cannot be well‐defined on computed tomography (CT). Diagnostic sequences are increasingly being adapted for radiation therapy planning, such as the use of heavily T2‐weighted 3D SPACE (Sampling Perfection with Application optimised Contrasts using different flip angle Evolution) sequence for cranial nerve identification in head and neck tumour treatment planning. Methods A 3D isotropic T2 SPACE sequence used for cranial nerve identification was adapted for radiation therapy purposes. Distortion was minimised using a spin‐echo‐based sequence, 3D distortion correction, isocentre scanning and an increased readout bandwidth. Radiation therapy positioning was accounted for by utilising two small flex, 4‐channel coils. The protocol was validated for cranial nerve identification in clinical applications and distortion minimisation using an MRI QA phantom. Results Normal anatomy of the cranial nerves CI‐CIX, were presented, along with a selection of clinical applications and abnormal anatomy. The usefulness of cranial nerve identification is discussed for several case studies, particularly in proximity to tumours extending into the base of skull region. In‐house testing validated that higher bandwidths of 600 Hz resulted in minimal displacement well below 1 mm. Conclusion The use of MRI for radiation therapy planning allows for greater individualisation and prediction of patient outcomes. Dose reduction to cranial nerves can decrease late side effects such as cranial neuropathy. In addition to current applications, future directions include further applications of this technology for radiation therapy treatments.

Abstract Purpose Caring for someone with cancer has a significant impact on usual routines, including caregivers' ability to maintain their own health and wellbeing. Caregivers living in rural areas face additional challenges in supporting someone with cancer, and little is known about the impact of caregiving on the health behaviors of rural caregivers. Therefore, this study explored how caring for someone with cancer affected rural caregivers' health behaviors. Methods Through semi‐structured interviews, 20 rural caregivers described changes in their health behaviors while caring for someone with cancer and the factors underlying these changes. Specific prompts were provided for diet, physical activity, alcohol, smoking, sleep, social connection and leisure, and accessing health care when needed. Interviews were audio‐recorded and transcribed verbatim. Content analysis was used to identify changes in health behaviors and the factors underlying these changes. The factors identified were mapped to the socioecological framework, identifying areas for intervention across multiple levels (individual, interpersonal, organizational, community, and policy). Results Rural caregivers reported both positive and negative changes to their diet, physical activity, alcohol, and smoking. Sleep, social connection and leisure, and accessing health care were negatively impacted since becoming a caregiver. Conclusions Designing interventions to address rural caregivers' coping strategies, reduce carer burden and fatigue, improve access to cooking and exercise facilities and social support while away from home, reduce the need to travel for treatment, and increase the financial support available could yield widespread benefits for supporting the health and wellbeing of rural caregivers.

Abstract Background This study aimed to compare sublingual microcirculatory parameters between anesthetized pigs and conscious adult humans using sidestream darkfield videomicroscopy. The overarching aim of the work was to validate the pig as an experimental model of changes in microcirculatory function following traumatic haemorrhagic shock and resuscitation. Methods Fourteen large white pigs and 14 humans were recruited for the study. Sublingual sidestream darkfield videomicroscopy clips were captured in anesthetized pigs and conscious humans. Clips underwent manual analysis in Automated Vascular Analysis 3.2 software. The total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPVs) and microvascular flow index (MFI) were quantified. An independent samples t test was used for between species comparison of microcirculatory parameters. Results and Conclusions Conscious humans had a significantly lower TVD, PVD and MFI than anesthetized pigs. No significant difference in PPVs was observed between the species. Perfusion of the microcirculation is a critical determinant of tissue metabolic function and viability. Whilst it may not be surprising that some interspecies differences in the sublingual microcirculatory anatomy were identified between pig and human subjects, it is interesting to report the insignificant difference in PPVs. This direct microcirculatory measure represents a relative change which should hold translatable value across species. We therefore conclude the pig is a suitable model for microcirculatory research and may be a suitable species to investigate changes in microcirculatory perfusion following perturbations in cardiovascular homeostasis, for example during traumatic haemorrhagic shock and resuscitation.

Abstract Introduction People living with long‐term neurological conditions (LTNCs) have complex needs that demand intensive care coordination between sectors. This review aimed to establish if integrated care improves outcomes for people, and what characterises successful interventions. Methods A systematic review of the literature was undertaken evaluating multisectoral integrated care interventions in people living with Parkinson's disease (PD), Multiple Sclerosis (MS) and Huntington's disease (HD). Strength of evidence was rated for the different outcomes. Results A total of 15 articles were included, reporting on 2095 patients and caregivers, finding that integrated care can improve people's access to resources and reduce patients' depression. UK studies indicated improvements in patients' quality of life, although the international literature was inconclusive. Few programmes considered caregivers' outcomes, reporting no difference or even worsening in depression, burden and quality of life. Overall, the evidence showed a mismatch between people's needs and outcomes measured, with significant outcomes (e.g., self‐management, continuity of care, care experience) lacking. Successful programmes were characterised by expert knowledge, multisectoral care coordination, care continuity and a person‐centred approach. Conclusions The impact of integrated care programmes on people living with LTNCs is limited and inconclusive. For a more person‐centred approach, future studies need to assess integrated care from a service‐user perspective. Patient and Public Contribution Thirty people living with LTNCs were involved in this review, through defining research questions, validating the importance of the project, and increasing the researchers' understanding on what matters to service users. A patient and public involvement subgroup of representatives with lived experience on PD, MS and HD identified the need for more person‐centred integrated care, with specific concerns over care fragmentation, care duplication and care continuity. This was key to data analysis and formulating the characteristics of successful and unsuccessful integrated care programmes from the perspective of service users. The discrepancy between service users' needs and the outcomes assessed in the literature point to user‐driven research as the solution to address what matters to patients and caregivers.

Abstract The economic and methodological efficiencies of environmental DNA (eDNA) based survey approaches provide an unprecedented opportunity to assess and monitor aquatic environments. However, instances of inadequate communication from the scientific community about confidence levels, knowledge gaps, reliability, and appropriate parameters of eDNA‐based methods have hindered their uptake in environmental monitoring programs and, in some cases, has created misperceptions or doubts in the management community. To help remedy this situation, scientists convened a session at the Second National Marine eDNA Workshop to discuss strategies for improving communications with managers. These include articulating the readiness of different eDNA applications, highlighting the strengths and limitations of eDNA tools for various applications or use cases, communicating uncertainties associated with specified uses transparently, and avoiding the exaggeration of exploratory and preliminary findings. Several key messages regarding implementation, limitations, and relationship to existing methods were prioritized. To be inclusive of the diverse managers, practitioners, and researchers, we and the other workshop participants propose the development of communication workflow plans, using RACI (Responsible, Accountable, Consulted, Informed) charts to clarify the roles of all pertinent individuals and parties and to minimize the chance for miscommunications. We also propose developing decision support tools such as Structured Decision‐Making (SDM) to help balance the benefits of eDNA sampling with the inherent uncertainty, and developing an eDNA readiness scale to articulate the technological readiness of eDNA approaches for specific applications. These strategies will increase clarity and consistency regarding our understanding of the utility of eDNA‐based methods, improve transparency, foster a common vision for confidently applying eDNA approaches, and enhance their benefit to the monitoring and assessment community.

Abstract Background Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD). Methods Infants with and without a FH of autism and/or ADHD, due to a first‐degree relative with either or both conditions, were recruited at 5 or 10 months. Three year outcomes were characterised using latent profile analysis (LPA) across measures of cognitive ability, adaptive functioning and autism, ADHD and anxiety traits (n = 131). We additionally ran an LPA using only autism and ADHD measures, and the broader LPA in an independent cohort (n = 139) and in both cohorts combined (n = 270). Results A Low Developmental Level + High Behavioural Concerns class had elevated autism, ADHD and anxiety scores, low cognitive and adaptive function, and included all but one child with autism. A Low Developmental Level + Typical Behaviour class had average cognitive ability and typical behaviour but low adaptive function. A Typical Developmental Level + Some Behavioural Concerns class had average cognitive and adaptive function but slightly elevated behaviour scores. A High Developmental Level + Typical Behaviour class had above average cognitive ability and typical behaviour. All four LPAs identified classes characterised by combinations of either, or both, Low Development Level and elevated behaviour scores, as well as a typically developing class. No classes had elevated autism or ADHD traits in isolation. Conclusions Some infants with a FH of autism or ADHD have atypical developmental and behavioural outcomes, but do not show strong autism or ADHD traits in isolation. The field needs to recalibrate aims and methods to embrace the broader transdiagnostic pattern of outcomes seen in these infants.

Abstract Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer‐related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non‐curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post‐treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Abstract Introduction In this study, we aimed to investigate the feasibility of gadoxetate low‐temporal resolution (LTR) DCE‐MRI for voxel‐based hepatic extraction fraction (HEF) quantification for liver sparing radiotherapy using a deconvolution analysis (DA) method. Methods The accuracy and consistency of the deconvolution implementation in estimating liver function was first assessed using simulation data. Then, the method was applied to DCE‐MRI data collected retrospectively from 64 patients (25 normal liver function and 39 cirrhotic patients) to generate HEF maps. The normal liver function patient data were used to measure the variability of liver function quantification. Next, a correlation between HEF and ALBI score (a new model for assessing the severity of liver dysfunction) was assessed using Pearson's correlation. Differences in HEF between Child‐Pugh score classifications were assessed for significance using the Kruskal–Wallis test for all patient groups and Mann–Whitney U‐test for inter‐groups. A statistical significance was considered at a P‐value

Abstract Aim The aim of the study was to reach consensus on modifiable risk factors for a novel system of care to address Manifestations of Frailty in hospitalized older adults. Design Consensus study. Method A modified nominal group technique, incorporating expert group face‐to‐face interaction, review of existing evidence and pre/post‐meeting questionnaire completion was undertaken November 2019–February 2020. Results Seventy‐one risk factors, within seven risk factor domains (pain, medication, fluid and nutrition intake, mobility, elimination, infection, additional patient factors) were considered. It was agreed that 44 risk factors incorporating patient, organizational and environmental risk factors were modifiable and should be included in a novel system of care.

Abstract Pigs are commonly maintained on total intravenous anaesthesia when used in comparative medical research to study controlled manual ventilation of the lung. In this case study, four pigs were anaesthetised with a total intravenous anaesthetic infusion of alfaxalone and dexmedetomidine for up to 24 h whilst being mechanically ventilated. Cardiovascular parameters, blood gas values and body temperature were minimally affected throughout the anaesthetic period. Additional analgesia is recommended when utilising this drug combination for procedures that involve noxious stimuli.

Abstract Background Migrant and ethnic inequalities in maternal and perinatal mortality persist across high‐income countries. Addressing social adversity and inequities across the childbirth trajectory cannot be left to chance and the good intentions of practitioners. Robust, evidence‐based tools designed to address inequity by enhancing both the quality of provision and the experience of care are needed. Methods An inductive modelling approach was used to develop a new evidence‐based conceptual model of woman–midwife relationships, drawing on data from an ethnographic study of relationships between migrant Pakistani women and midwives, conducted between 2013 and 2016 in South Wales, UK. Key analytic themes from early data were translated into social–ecological concepts, and a model was developed to represent how these key themes interacted to influence the woman–midwife relationship. Results Three key concepts influencing the woman–midwife relationship were developed from the three major themes of the underpinning research: (1) Healthcare System; (2) Culture and Religion; and (3) Family Relationships. Two additional weaving concepts appeared to act as a link between these three key concepts: (1) Authoritative Knowledge and (2) Communication of Information. Social and political factors were also considered as contextual factors within the model. A visual representation of this model was developed and presented. Conclusions The model presented in this paper, along with future work to further test and refine it in other contexts, has the potential to impact on inequalities by facilitating future discussion on cultural issues, encouraging collaborative learning and knowledge production and providing a framework for future global midwifery practice, education and research. Patient or Public Contribution At the outset of the underpinning research, a project involvement group was created to contribute to study design and conduct. This group consisted of the three authors, an Advocacy Officer at Race Equality First and an NHS Consultant Midwife. This group met regularly throughout the research process, and members were involved in discussions regarding ethical/cultural/social issues, recruitment methods, the creation of participant information materials, interpretation of data and the dissemination strategy. Ideas for the underpinning research were also discussed with members of the Pakistani community during community events and at meetings with staff from minority ethnic and migrant support charities (BAWSO, Race Equality First, The Mentor Ring). Local midwives contributed to study design through conversations during informal observations of antenatal appointments for asylum seekers and refugees.

Abstract White‐nose syndrome is a fungal disease that is threatening bat populations across North America. The disease primarily affects cave‐hibernating bats by depleting fat reserves during hibernation and causing a range of other physiological consequences when immune responses are suppressed. Since it was first detected in 2006, the disease has killed millions of bats and is responsible for extensive local extinctions. To better understand the effects of white‐nose syndrome on various bat species, we analyzed summer acoustic survey data collected from 2016 to 2020 at nine US National Parks within the Great Lakes region. We examined the effect that white‐nose syndrome, time of the year relative to pup volancy, habitat type, and regional variation (i.e., park) have on the acoustic abundance (i.e., mean call abundance) of six bat species. As expected, little brown bat (Myotis lucifugus) and northern long‐eared bat (Myotis septentrionalis), both hibernating species, experienced a significant decline in acoustic abundance following white‐nose syndrome detection. We observed a significant increase in acoustic abundance as white‐nose syndrome progressed for hoary bats (Lasiurus cinereus) and silver‐haired bats (Lasionycteris noctivagans), both migratory species that are not impacted by the disease. Contrary to our predictions, we observed an increase in big brown bat (Eptesicus fuscus; hibernating) acoustic abundance and a decrease in eastern red bat (Lasiurus borealis; migratory) acoustic abundance following the detection of white‐nose syndrome. We did not observe any significant changes after the onset of white‐nose syndrome in the seasonal patterns of acoustic activity related to pup volancy, suggesting that production or recruitment of young may not be affected by the disease. Our results suggest that white‐nose syndrome is affecting the acoustic abundance of certain species; however, these changes may not be a result of reduced reproductive success caused by the disease. In addition, species population dynamics may be indirectly affected by white‐nose syndrome as a result of reduced competition or a foraging niche release. We also found that for parks located at higher latitudes, little brown bat and northern long‐eared bat were more likely to experience greater declines in acoustic abundance as a result of white‐nose syndrome. Our work provides insight into species‐specific responses to white‐nose syndrome at a regional scale and examines factors that may facilitate resistance or resiliency to the disease.

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows: identify available systematic reviews and randomised controlled trials on interventions targeting health or social needs of the people aged over 80; identify qualitative studies relating to the experiences of people aged over 80 of interventions that target their health or social needs; identify areas where systematic reviews are needed; identify gaps in evidence where further primary research is needed; assess equity considerations (using the PROGRESS plus criteria) in available systematic reviews, randomised trials and qualitative studies of identified interventions; assess gaps and evidence related to health equity.

Abstract Environmental DNA (eDNA) is an emerging and powerful method for use in marine research, conservation, and management, yet time‐ and resource‐intensive protocols limit the scale of implementation. Long‐range autonomous underwater vehicles equipped with autonomous environmental sample processors (LRAUV‐ESPs) provide a new means for scaling up marine eDNA sample collection and processing. Here, we used eDNA metabarcoding of four marker genes (mitochondrial 12S rRNA, bacterial and archaeal 16S rRNA, nuclear 18S rRNA, and mitochondrial COI), which encompass the diversity of marine species from microbes to vertebrates, to demonstrate the efficacy of an LRAUV‐ESP in sampling eDNA and assessing community structure in the Monterey Bay National Marine Sanctuary. The sequencing results from samples that were autonomously collected were comparable with those collected from a ship at similar locations, times, and depths, supporting previous results that found no significant differences using targeted qPCR. This study demonstrates the potential of equipping autonomous underwater vehicles with ESPs to greatly expand the scale of eDNA sample collection and processing and provide much needed information regarding the changing spatial and temporal patterns of marine biodiversity, especially in many data‐poor regions of the world's oceans.

Abstract Long‐term data are beneficial for monitoring the conservation status of species. Assessments of population change over recent periods of fixed duration will, however, be subject to ‘shifting baselines’, where the accepted norm for the population at the start of the period already represents a reduction from historical levels. International Union for Conservation of Nature Red List criteria for categorizing conservation threat rely on assessing declines against quantitative thresholds, generally measured over 10 years, as indications of the likelihood of extinction in the near future. By contrast, legal frameworks such as the European Habitats Directive require states to achieve and sustain ‘Favourable Conservation Status’ for protected species, while domestic conservation legislation can have more diverse objectives and mechanisms, based on local contexts that extend beyond biological or quantitative criteria. We explore the challenges associated with assessing the risk of extinction and the conservation status that arise from the availability of long‐term monitoring data for hazel dormice Muscardinus avellanarius in the United Kingdom. Numbers of adult dormice counted in the National Dormouse Monitoring Programme are in ongoing decline, amounting to an overall decline of 78% (95% confidence interval = 72%–84%) over 27 years, 1994–2020. If the observed annual rate of decline of 5.7% (95% CI = 4.7%–6.8%) were to continue unabated, dormouse counts would decline by >90% from 1994 to 2034. Despite this, the species would never be categorized as Endangered, under IUCN criteria, which specify a reduction of >50% within 10 years. While such chronic decline may not indicate imminent risk of extinction, justifying a higher Red List category, it is a demonstration of unfavourable conservation status at a national scale. Prioritization based on demonstration of such chronic declines might direct more effective action towards species conservation at a point when their recovery is more attainable, rather than attempting later to reverse a journey to the brink of extinction when the species is finally ‘Endangered’.

Abstract Introduction The prostatic urethra is an organ at risk for prostate radiotherapy with genitourinary toxicities a common side effect. Many external beam radiation therapy protocols call for urethral sparing, and with modulated radiotherapy techniques, the radiation dose distribution can be controlled so that maximum doses do not fall within the prostatic urethral volume. Whilst traditional diagnostic MRI sequences provide excellent delineation of the prostate, uncertainty often remains as to the true path of the urethra within the gland. This study aims to assess if a high‐resolution isotropic 3D T2 MRI series can reduce inter‐observer variability in urethral delineation for radiotherapy planning. Methods Five independent observers contoured the prostatic urethra for ten patients on three data sets; a 2 mm axial CT, a diagnostic 3 mm axial T2 TSE MRI and a 0.9 mm isotropic 3D T2 SPACE MRI. The observers were blinded from each other’s contours. A Dice Similarity Coefficient (DSC) score was calculated using the intersection and union of the five observer contours vs an expert reference contour for each data set. Results The mean DSC of the observer vs reference contours was 0.47 for CT, 0.62 for T2 TSE and 0.78 for T2 SPACE (P

Cellular phenotype plasticity between the epithelial and mesenchymal states has been linked to metastasis and heterogeneous responses to cancer therapy, and remains a challenge for the treatment of triple‐negative breast cancer (TNBC). Here, we used isogenic human breast epithelial cell lines, D492 and D492M, representing the epithelial and mesenchymal phenotypes, respectively. We employed a CRISPR‐Cas9 loss‐of‐function screen targeting a 2240‐gene ‘druggable genome’ to identify phenotype‐specific vulnerabilities. Cells with the epithelial phenotype were more vulnerable to the loss of genes related to EGFR‐RAS‐MAPK signaling, while the mesenchymal‐like cells had increased sensitivity to knockout of G2‐M cell cycle regulators. Furthermore, we discovered knockouts that sensitize to the mTOR inhibitor everolimus and the chemotherapeutic drug fluorouracil in a phenotype‐specific manner. Specifically, loss of EGFR and fatty acid synthase (FASN) increased the effectiveness of the drugs in the epithelial and mesenchymal phenotypes, respectively. These phenotype‐associated genetic vulnerabilities were confirmed using targeted inhibitors of EGFR (gefitinib), G2‐M transition (STLC), and FASN (Fasnall). In conclusion, a CRISPR‐Cas9 loss‐of‐function screen enables the identification of phenotype‐specific genetic vulnerabilities that can pinpoint actionable targets and promising therapeutic combinations.

Societal Impact Statement Understanding of tropical forests has been revolutionized by monitoring in permanent plots. Data from global plot networks have transformed our knowledge of forests’ diversity, function, contribution to global biogeochemical cycles, and sensitivity to climate change. Monitoring has thus far been concentrated in rain forests. Despite increasing appreciation of their threatened status, biodiversity, and importance to the global carbon cycle, monitoring in tropical dry forests is still in its infancy. We provide a protocol for permanent monitoring plots in tropical dry forests. Expanding monitoring into dry biomes is critical for overcoming the linked challenges of climate change, land use change, and the biodiversity crisis.

Abstract Objective To estimate muscle oxygen uptake and quantify fatigue during exercise in ambulatory individuals with spinal muscular atrophy (SMA) and healthy controls. Methods Peak aerobic capacity (VO2peak) and workload (Wpeak) were measured by cardiopulmonary exercise test (CPET) in 19 ambulatory SMA patients and 16 healthy controls. Submaximal exercise (SME) at 40% Wpeak was performed for 10 minutes. Change in vastus lateralis deoxygenated hemoglobin, measured by near‐infrared spectroscopy, determined muscle oxygen uptake (ΔHHb) at rest and during CPET and SME. Dual energy X‐ray absorptiometry assessed fat‐free mass (FFM%). Fatigue was determined by percent change in workload or distance in the first compared to the last minute of SME (FatigueSME) and six‐minute walk test (Fatigue6MWT), respectively. Results ΔHHb‐PEAK, ΔHHb‐SME, VO2peak, Wpeak, FFM%, and 6MWT distance were lower (P

Reduced expression of the uptake transporter, OCTN1 (SLC22A4), has been reported as a strong predictor of poor event‐free and overall survival in multiple cohorts of patients with acute myeloid leukemia (AML) receiving the cytidine nucleoside analog, cytarabine (Ara‐C). To further understand the mechanistic basis of interindividual variability in the functional expression of OCTN1 in AML, we hypothesized a mechanistic connection to DNA methylation‐based epigenetic repression of SLC22A4. We found increased basal SLC22A4 methylation was associated with decreased Ara‐C uptake in AML cell lines. Pre‐treatment with hypomethylating agents, 5‐azacytidine, or decitabine, restored SLC22A4 mRNA expression, increased cellular uptake of Ara‐C, and was associated with increased cellular sensitivity to Ara‐C compared with vehicle‐treated cells. Additionally, lower SLC22A4 methylation status was associated with distinct clinical advantages in both adult and pediatric patients with AML. These findings suggest a regulatory mechanism is involved in the interindividual variability in response to Ara‐C, and provides a basis for the integration of hypomethylating agents into Ara‐C‐based treatment regimens.

Abstract Releasing gamebirds in large numbers for sport shooting may directly or indirectly influence the abundance, distribution and population dynamics of native wildlife. The abundances of generalist predators have been positively associated with the abundance of gamebirds. These relationships have implications for prey populations, with the potential for indirect impacts of gamebird releases on wider biodiversity. To understand the basis of these associations, we investigated variation in territory size, prey provisioning to chicks, and breeding success of common buzzards Buteo buteo, and associations with variation in the abundances of free‐roaming gamebirds, primarily pheasants Phasianus colchicus, and of rabbits Oryctolagus cuniculus and field voles Microtus agrestis, as important prey for buzzards. The relative abundance of gamebirds, but not those of rabbits or voles, was weakly but positively correlated with our index of buzzard territory size. Gamebirds were rarely brought to the nest. Rabbits and voles, and not gamebirds, were provisioned to chicks in proportion to their relative abundance. The number of buzzard chicks increased with provisioning rates of rabbits, in terms of both provisioning frequency and biomass, but not with provisioning rates for gamebirds or voles. Associations between the abundances of buzzards and gamebirds may not be a consequence of the greater availability of gamebirds as prey during the buzzard breeding season. Instead, the association may arise either from habitat or predator management leading to higher densities of alternative prey (in this instance, rabbits), or from greater availability of gamebirds as prey or carrion during the autumn and winter shooting season. The interactions between gamebird releases and associated practices of predator control and shooting itself require better understanding to more effectively intervene in any one aspect of this complex social‐ecological system.