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Abstract Emergency admissions (EA), where a patient requires urgent in-hospital care, are a major challenge for healthcare systems. The development of risk prediction models can partly alleviate this problem by supporting primary care interventions and public health planning. Here, we introduce SPARRAv4, a predictive score for EA risk that will be deployed nationwide in Scotland. SPARRAv4 was derived using supervised and unsupervised machine-learning methods applied to routinely collected electronic health records from approximately 4.8M Scottish residents (2013-18). We demonstrate improvements in discrimination and calibration with respect to previous scores deployed in Scotland, as well as stability over a 3-year timeframe. Our analysis also provides insights about the epidemiology of EA risk in Scotland, by studying predictive performance across different population sub-groups and reasons for admission, as well as by quantifying the effect of individual input features. Finally, we discuss broader challenges including reproducibility and how to safely update risk prediction models that are already deployed at population level.

Summary: Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.

There is a need for operational decision-making methodologies applicable at local management scales which are inclusive and enable the integration of plural values, knowledges and perspectives of co-produced ecosystem services. Here we describe a deliberative scenario analysis method using ‘management intervention bundles’ as distinct scenarios to assess the perceived impact of changing management on woodland ecosystem services. We used three hypothetical future management scenarios, Biodiversity Conservation, People Engagement and Austerity, alongside scenarios of the Past, Present and an existing Management Plan. We assessed the perceived impacts of these scenarios on 11 ecosystem services using local expert workshops in six sites across Scotland. The experts were chosen to represent a range of different perspectives, from biodiversity to the local economy, community concerns and recreation. Overall, Management Plan, Biodiversity Conservation and People Engagement scenarios performed significantly better than Past, Present and Austerity scenarios. Further quantitative and in-depth qualitative analysis revealed trade-offs and noteworthy patterns. We explore some of these key trade-offs and patterns and argue that our methodology has potential to be an effective tool for local managers to support local decision-making at management scales for co-produced ecosystem services. Our methodology enabled a diverse group of local experts to express and deliberate a range of values, experiences and viewpoints. This knowledge sharing and collective learning allowed the development of shared values and perspectives, which are thought to be critical in more equitable and inclusive decision-making.

This study focuses on the interplay between specific relations to nature and more abstract concepts and values regarding the nature of humans and nature and the relationships between humans and nature. We conducted Q sorts and interviews with 25 individuals who were growing plants in gardens, allotments or different kinds of agricultural settings in Scotland. We identified three discourses representing different ways of conceptualising human-nature relationships, namely: 1) Guardianship of fragile nature; 2) Partnership with powerful nature; and 3) Rational anthropocentric management. The different discourses implied different ways of approaching environmental issues and the right way for humans to relate to nature. While the three discourses represented different understandings of human-nature relations, there was also overlap and similarities amongst them. Cross-cutting themes included the notion of balance as a central aim of many ‘growers’ and learning as an important part of growing plants. The study also showed that the respondents’ own practices did not neatly map on to single abstract perspectives, with individuals often drawing on elements of different discourses and commenting on their contradictions. Ultimately, this connected to the question on how to find the right balance between human and non-human interests. Bringing in a relational understanding and acknowledging the plurality of perspectives on human-nature relations, as well as their contradictions, overlaps and tensions, can open up the space for alternative narratives to be reflected in policies but also that structural and systemic changes are required for people to cultivate more benign relations with other-than-humans.

Context: Left atrial appendage closure (LAAC) was developed as a novel stroke prevention alternative for patients with atrial fibrillation, particularly for those not suitable for long-term oral anticoagulant therapy. Traditionally, general anesthesia (GA) has been more commonly used primarily due to the necessity of transesophageal echocardiography. Aims: Compare trends of monitored anesthesia care (MAC) versus GA for percutaneous transcatheter LAAC with endocardial implant and assess for independent variables associated with primary anesthetic choice. Settings and Design: Multi-institutional data collected from across the United States using the National Anesthesia Clinical Outcomes Registry. Material and Methods: Retrospective data analysis from 2017–2021. Statistical Analysis Used: Independent-sample t tests or Mann–Whitney U tests were used for continuous variables and Chi-square tests or Fisher’s exact test for categorical variables. Multivariate logistic regression was used to assess patient and hospital characteristics. Results: A total of 19,395 patients underwent the procedure, and 352 patients (1.8%) received MAC. MAC usage trended upward from 2017–2021 (P < 0.0001). MAC patients were more likely to have an American Society of Anesthesiologists (ASA) physical status of≥ 4 (33.6% vs 22.89%) and to have been treated at centers in the South (67.7% vs 44.2%), in rural locations (71% vs 39.5%), and with lower median annual percutaneous transcatheter LAAC volume (102 vs 153 procedures) (all P < 0.0001). In multivariate analysis, patients treated in the West had 85% lower odds of receiving MAC compared to those in the Northeast (AOR: 0.15; 95% CI 0.03–0.80, P = 0.0261). Conclusions: While GA is the most common anesthetic technique for percutaneous transcatheter closure of the left atrial appendage, a small, statistically significant increase in MAC occurred from 2017–2021. Anesthetic management for LAAC varies with geographic location.

Abstract The real-world measurement of minimum foot clearance (mFC) during the swing phase of gait is critical in efforts to understand and reduce the risk of trip-and-fall incidents in populations with gait impairments. Past research has focused on measuring clearance of a single point on a person’s foot, typically the toe—however, this may overestimate mFC and may even be the wrong region of the foot in cases of gait impairments or interventions. In this work, we present a novel method to reconstruct the swing-phase trajectory of an arbitrary number of points on a person’s shoe and estimate the instantaneous height and location of whole-foot mFC. This is achieved using a single foot-mounted inertial sensor and personalized shoe geometry scan, assuming a rigid-body IMU-shoe system. This combination allows collection and analysis using out-of-lab tests, potentially including clinical environments. Validation of single marker location using the proposed method vs. motion capture showed height errors with bias less than 0.05 mm, and 95% confidence interval of − 8.18 to + 8.09 mm. The method is demonstrated in an example data set comparing different interventions for foot drop, and it shows clear differences among no intervention, functional electrical stimulation, and ankle–foot orthosis conditions. This method offers researchers and clinicians a rich understanding of a person’s gait by providing objective 3D foot kinematics and allowing a unique opportunity to view the regions of the foot where minimum clearance occurs. This information can contribute to a more informed recommendation of specific interventions or assistive technology than is currently possible in standard clinical practice.

Tapping maple trees to produce maple syrup offers many benefits for producers. Since potential pro­ducers likely value some of these benefits more than others, communicators seeking to encourage more people to begin maple syrup production should use messaging that emphasizes the benefits that best resonate with potential producers. To test this strategy, known as emphasis message framing, we ran Facebook advertisements aimed at people liv­ing in Wisconsin, the fourth-leading U.S. state in annual maple syrup production, to test four mes­sage frames: building community, achieving food self-sufficiency, engaging in the lifestyle of working the land, and spending time in nature. Overall, the frame of working the land was the most effective in terms of link clicks and post reactions. However, among people ages 55+, who were more likely than younger Facebook users to engage with our adver­tisements, the food self-sufficiency frame received the most clicks while the nature frame received the most post reactions. In all age groups, women were more likely to click on our ads than men. These findings can be applied to future efforts to grow the number of small-scale maple syrup producers in Wisconsin and beyond. Additionally, our results underscore the importance of establishing a clear goal and segmenting audiences when designing social media campaigns. Our methods can serve as a blueprint for anyone seeking to empirically test the effectiveness of different message frames in public outreach related to agriculture or food systems.

Abstract Background Cerebrovascular accidents (CVAs) in dogs are diagnosed using magnetic resonance imaging (MRI). This modality is sometimes unavailable, and CVAs can resemble other lesions on MRI. D‐dimer concentration and thromboelastography (TEG) are utilized in human medicine in addition to diagnostic imaging to support diagnosis of CVAs, but their use in veterinary patients has not been assessed. Objective Assess utility of blood D‐dimer concentration and TEG in supporting the imaging diagnosis of CVAs in dogs. Animals Sixty‐eight client‐owned dogs with neurologic signs that had brain MRI and D‐dimer concentration or TEG performed. Methods Multicenter, retrospective study. The incidence of abnormal D‐dimer concentration or TEG was compared between patients with MRI evidence of CVA and a control population. Analysis methods included Fisher's exact test or Chi‐squared test for association and comparison of independent proportions. Results Neither D‐dimer concentration nor TEG was significantly associated with a CVA (P = .38 and .2, respectively). D‐dimer testing was performed in a low‐risk population and showed low sensitivity (30.8%; 95% confidence interval [CI], 10%‐61%) and high specificity (86.4%; 95% CI, 64%‐96%) for CVA diagnosis. Thromboelastography was performed in a high‐risk population and showed moderate sensitivity (64.3%; 95% CI, 44%‐81%) and specificity (66.7%; 95% CI, 24%‐94%) for CVA diagnosis. Abnormal D‐dimer concentration or TEG were not helpful in differentiating hemorrhagic from ischemic stroke (P = .43 and .41, respectively). Conclusions Although blood D‐dimer concentration or TEG alone are not diagnostic of CVAs in dogs, a positive D‐dimer result supports additional testing for CVA.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1–157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7–174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977–0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Abstract Background Proton pump inhibitors can cause diarrhea and a transient increase in fecal dysbiosis index in dogs. It is unknown if concurrent probiotic administration mitigates these effects. Objective/Hypothesis To assess the fecal Canine Microbial Dysbiosis Index (CMDI), fecal short chain fatty acid (SCFA), and fecal calprotectin concentrations in dogs administered esomeprazole with and without a probiotic. Animals Eleven healthy dogs. Methods Prospective, within‐subjects before and after study. All dogs received 7‐day courses of esomeprazole (1 mg/kg PO q 24h) alone followed by esomeprazole with a probiotic (15 billion CFU/kg), separated by a 4‐week washout period. Data were compared between phases using mixed effects ANOVA or generalized estimating equations with post‐hoc Holm adjustment for 2‐way comparisons. Results Compared to baseline (mean CMDI −2.66, SD 3.04), fecal CMDI was not different with esomeprazole administration alone (mean CMDI −1.48, SD 3.32, P = .08), but there was a significant increase (Diff 3.05, 95% CI [1.37, 4.74], P

Background: To evaluate if Hounsfield units (HU) measured on preoperative computed tomography (CT) scans at the anatomic neck of the proximal humerus correlates with intraoperative findings of the “thumb test” in assessment of bone quality in shoulder arthroplasty patients. Methods: Primary anatomic total shoulder and reverse total shoulder arthroplasty patients from 2019-2022 with an available preoperative CT scan of the operative shoulder were prospectively enrolled at a single center with 3 surgeons who perform shoulder arthroplasty. The “thumb test” was performed intraoperatively; a positive test signified “good bone.” Demographic information, including prior dual x-ray absorptiometry scans, was extracted from the medical record. HU at the cut surface of the proximal humerus were calculated, as was cortical bone thickness on preoperative CT. Fracture risk assessment tool (FRAX) scores were calculated for 10-year risk of osteoporotic fracture. Results: A total of 149 patients were enrolled. Mean age was 67.6 ± 8.5 years with 69 (46.3%) being males. Patients with a negative thumb test were significantly older (72.3 ± 6.6 vs. 66.5 ± 8.6 years; P

Abstract African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC–MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Abstract A high percentage of island floras are at risk of extinction and have been reduced to relic populations, often in remote hard‐to‐reach areas. Uncrewed aircraft systems (UAS aka drones) are now being utilized to assist in the survey and collection of rare plants in inaccessible areas or vertical cliff habitats. Here, we test the application of this technology for conservation of 23 plant taxa in three oceanic island hotspots: Hawaiʻi, Madeira and the Republic of Palau. We collect high‐resolution imagery using a small UAS to document the distribution and abundance of vascular flowering plants. Location information is then used to map and assess plant populations. Depending on the terrain, collections are completed using either traditional rope techniques or newly developed remote drone‐based collection methods. Over the course of 6 years, we have greatly expanded our knowledge of rare and endangered species, while increasing survey efficiency and staff safety. Most importantly, this work has had a large impact on the conservation of critically endangered plants. Although using drones for botanical conservation comes with limits and challenges, we see great potential in the continued employment of these techniques wherever plants are growing on cliffs or in other hard‐to‐reach areas.

Abstract The values that people hold are thought to be key in bringing about the transformative change needed to halt biodiversity loss. Caring for nature has been conceptualised as a relational value and is thought to be largely shaped in childhood and adolescence. Relational values, arising from human–nature interactions, are increasingly being viewed as critical to halting biodiversity loss. However, caring for nature is not seen as sufficient to bring about pro‐environmental behaviour; a sense of efficacy is thought to also be required. As human societies become more urbanised, the greenspaces in and around our cites will become increasingly important as spaces where people can experience human–nature interactions. In our study, we explore participatory video (PV) as a tool for (a) providing new insights on young people's experience of greenspace, (b) enabling meaningful and transformative human–nature interactions and (c) building efficacy. The films produced by the young people showed that greenspaces were not for them; they were associated with violence and bullying or simply thought of as ‘boring’. The study also provided unexpected evidence for the potential of PV, to not only transform the way previously disengaged young people viewed their local greenspace but also how they use it, benefit from it and begin to change their behaviours towards it. The PV process also enabled young people, individually and collectively, to connect with nature and experience activities that enhanced their efficacy, confidence and sense of empowerment. We go on to discuss the potential of PV to help leverage the transformative change necessary to halt biodiversity loss and build more sustainable futures. A free Plain Language Summary can be found within the Supporting Information of this article.

Abstract Background Individuals with certain chronic inflammatory lung diseases have a higher risk of developing lung cancer (LC). However, the underlying mechanisms remain largely unknown. Here, we hypothesized that chronic exposure to house dust mites (HDM), a common indoor aeroallergen associated with the development of asthma, accelerates LC development through the induction of chronic lung inflammation (CLI). Methods The effects of HDM and heat-inactivated HDM (HI-HDM) extracts were evaluated in two preclinical mouse models of LC (a chemically-induced model using the carcinogen urethane and a genetically-driven model with oncogenic Kras G12D activation in lung epithelial cells) and on murine macrophages in vitro. Pharmacological blockade or genetic deletion of the Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, caspase-1, interleukin-1β (IL-1β), and C–C motif chemokine ligand 2 (CCL2) or treatment with an inhaled corticosteroid (ICS) was used to uncover the pro-tumorigenic effect of HDM. Results Chronic intranasal (i.n) instillation of HDM accelerated LC development in the two mouse models. Mechanistically, HDM caused a particular subtype of CLI, in which the NLRP3/IL-1β signaling pathway is chronically activated in macrophages, and made the lung microenvironment conducive to tumor development. The tumor-promoting effect of HDM was significantly decreased by heat treatment of the HDM extract and was inhibited by NLRP3, IL-1β, and CCL2 neutralization, or ICS treatment. Conclusions Collectively, these data indicate that long-term exposure to HDM can accelerate lung tumorigenesis in susceptible hosts (e.g., mice and potentially humans exposed to lung carcinogens or genetically predisposed to develop LC).

For more than forty years, jurisprudence has been dominated by the Hart- Dworkin debate. The debate starts from the premise that our legal practices generate rights and obligations that are distinctively legal, and the question at issue is how the content of these rights and obligations is determined. Positivists say that their content is determined ultimately or exclusively by social facts. Anti-positivists say that moral facts must play a part in determining their content. In this essay, I argue that the debate rests on a mistake. Our legal practices do not generate rights and obligations that are distinctively legal. At best, they generate moral rights and obligations, some of which we label legal. I defend this view by drawing analogies with other normative practices, like making promises, posting rules, and playing games. And I try to explain why it looks like legal practices generate distinctively legal rights and obligations even though they do not. I conclude with some thoughts about the questions that jurisprudence should pursue in the wake of the Hart-Dworkin debate.

IntroductionMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic, multi-system disorder that is characterized by a substantial impairment in the activities that were well tolerated before the illness. In an earlier report, we had described three adult women who met criteria for ME/CFS and orthostatic intolerance, and had congenital or acquired cervical spinal stenosis. All three experienced substantial global improvements in their ME/CFS and orthostatic intolerance symptoms after recognition and surgical treatment of the cervical stenosis. After a several year period of improvement, one of the individuals in that series experienced a return of ME/CFS and orthostatic intolerance symptoms.Main symptoms and clinical findingsRadiologic investigation confirmed a recurrence of the ventral compression of the spinal cord due to a shift of the disc replacement implant at the involved cervical spinal level.Therapeutic interventionDecompression of the spinal cord with removal of the implant and fusion at the original C5-C6 level was once again followed by a similar degree of improvement in function as had been observed after the first operation.ConclusionThis recapitulation of the outcomes after surgical management of cervical stenosis provides further evidence in support of the hypothesis that cervical spinal stenosis can exacerbate pre-existing or cause new orthostatic intolerance and ME/CFS. Especially for those with refractory symptoms and neurological signs, surgical interventions may offer relief for selected patients with this complex condition.

Abstract The timing of snowmelt runoff is critical for water resource applications, but its spatiotemporal evolution remains poorly understood. We present a scalable approach to map snowmelt runoff onset using Sentinel‐1 synthetic aperture radar data for the past 8 years with 10 m spatial resolution and a median temporal resolution of 3.9 days. A systematic analysis of stratovolcanoes in the Western United States showed that snowmelt runoff onset is strongly dependent on elevation (r = 0.81), with a median runoff onset lapse rate of 4.9 days per 100 m of elevation gain. During the 2015 snow drought, we observed snowmelt runoff onset 25 days early relative to the 2015–2022 median. We document a median shift in snowmelt runoff onset of +2.0 days later in the year per year between 2016 and 2022. Our open‐source tools can be used to create snowmelt runoff onset maps anywhere on Earth.

Background: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood. Methods: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank (Stage 1). We followed-up well-imputed top signals from our Stage 1 analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts (Stage 2). We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms. Results: From our Stage 1 analysis, we report 56 signals at P

Abstract If necropolitics, according to Achille Mbembe, involves “contemporary forms of subjugation of life to the powers of death,” necropoetics, as proposed here, involves the poetic and gestural interruption of necropolitics. Starting out from a gesture that simulates the act of killing, I ask what sort of anthropology and corresponding mode of writing would be entailed if one were to imaginatively align oneself with that gesture and others like it as they traverse temporal, contextual, and intertextual thresholds - including that between life and death - and the racialized histories recalled thereby. The counter-fabulatory approach taken herein, in pitting the poetic (Black) subtexts of the iterations of this gesture against the varied modes of discourse - ethnographic (part I), historical (part II) and anthropological (part III) - that would capture them, seeks to performatively interrupt the pretense of a neutral language through which necropolitics passes for the continuation of history as usual.

The International Committee on Systematics of Prokaryotes (ICSP) discussed and rejected in 2020 a proposal to modify the International Code of Nomenclature of Prokaryotes to allow the use of gene sequences as type for naming prokaryotes. An alternative nomenclatural code, the Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode), which considers genome sequences as type material for naming species, was published in 2022. Members of the ICSP subcommittee for the taxonomy of the phylum Chlamydiae (Chlamydiota) consider that the use of gene sequences as type would benefit the taxonomy of microorganisms that are difficult to culture such as the chlamydiae and other strictly intracellular bacteria. We recommend the registration of new names of uncultured prokaryotes in the SeqCode registry.

Abstract Concepts such as ecosystem services and nature's contributions to people are frameworks for articulating the value of nature and biodiversity conservation. Yet it remains difficult to argue for the conservation of species and habitats where they are inconspicuous or ‘non‐charismatic’. This paper investigates the perceptions of a woodland area in rural western Scotland, designated for its high conservation value and characterised by habitats, rare species and species assemblages with limited appreciation by non‐experts and no obvious ‘utility’ value. Based on interviews with residents and visitors as well as workshops with participants representing different types of local expertise, we show how people experience and perceive the benefits from such woodlands. Overall, our study participants emphasised values and ecosystem services that benefitted humans, strongly drawing on stories of cultural or historical land use to argue for more material opportunities to be created. For those participants without ecological expertise, the designated conservation value, albeit respected and accepted, remained vague and bland. Participants also articulated a strong underlying development logic, pushing in some way for ‘more’ to be made from the woodlands so that more people could receive benefits from the woodland either directly (e.g. mental restoration; increased use for recreation) or indirectly (e.g. through creating jobs in the local tourism industry). Our findings suggest that managing for conservation alone might cause challenges in acceptability, especially where the species and habitats conserved are of little obvious value to the non‐specialist. At the same time, participants recognised that they valued the woodland being unique in some way, and that increasing the material use of the woods might harm the very essence of what made it special. Read the free Plain Language Summary for this article on the Journal blog.

In the past decade, photoacoustic (PA) imaging has attracted a great deal of popularity as an emergent diagnostic technology owing to its successful demonstration in both preclinical and clinical arenas by various academic and industrial research groups. Such steady growth of PA imaging can mainly be attributed to its salient features, including being non-ionizing, cost-effective, easily deployable, and having sufficient axial, lateral, and temporal resolutions for resolving various tissue characteristics and assessing the therapeutic efficacy. In addition, PA imaging can easily be integrated with the ultrasound imaging systems, the combination of which confers the ability to co-register and cross-reference various features in the structural, functional, and molecular imaging regimes. PA imaging relies on either an endogenous source of contrast (e.g., hemoglobin) or those of an exogenous nature such as nano-sized tunable optical absorbers or dyes that may boost imaging contrast beyond that provided by the endogenous sources. In this review, we discuss the applications of PA imaging with endogenous contrast as they pertain to clinically relevant niches, including tissue characterization, cancer diagnostics/therapies (termed as theranostics), cardiovascular applications, and surgical applications. We believe that PA imaging’s role as a facile indicator of several disease-relevant states will continue to expand and evolve as it is adopted by an increasing number of research laboratories and clinics worldwide.

The commercial cloud offers on-demand computational resources that could be revolutionary for the seismological community, especially as seismic datasets continue to grow. However, there are few educational examples for cloud use that target individual seismological researchers. Here, we present a reproducible earthquake detection and association workflow that runs on Microsoft Azure. The Python-based workflow runs on continuous time-series data using both template matching and machine learning. We provide tutorials for constructing cloud resources (both storage and computing) through a desktop portal and deploying the code both locally and remotely on the cloud resources. We report on scaling of compute times and costs to show that CPU-only processing is generally inexpensive, and is faster and simpler than using GPUs. When the workflow is applied to one year of continuous data from a mid-ocean ridge, the resulting earthquake catalogs suggest that template matching and machine learning are complementary methods whose relative performance is dependent on site-specific tectonic characteristics. Overall, we find that the commercial cloud presents a steep learning curve but is cost-effective. This report is intended as an informative starting point for any researcher considering migrating their own processing to the commercial cloud.

Summary: Many epidemiologic studies have identified important relationships between leukocyte telomere length (LTL) with genetics and health. Most of these studies have been significantly limited in scope by focusing predominantly on individual diseases or restricted to GWAS analysis. Using two large patient populations derived from Vanderbilt University and Marshfield Clinic biobanks linked to genomic and phenomic data from medical records, we investigated the inter-relationship between LTL, genomics, and human health. Our GWAS confirmed 11 genetic loci previously associated with LTL and two novel loci in SCNN1D and PITPNM1. PheWAS of LTL identified 67 distinct clinical phenotypes associated with both short and long LTL. We demonstrated that several diseases associated with LTL were related to one another but were largely independent from LTL genetics. Age of death was correlated with LTL independent of age. Those with very short LTL (1.5 SD) died 1.9 years (p = 0.0175) younger than those with average LTL. This is consistent with the PheWAS results showing diseases associating with both short and long LTL. Finally, we estimated that the genome (12.8%) and age (8.5%) explain the largest proportion of LTL variance, whereas the phenome (1.5%) and sex (0.9%) explained a smaller fraction. In total, 23.7% of LTL variance was explained. These observations provide the rationale for expanded research to understand the multifaceted correlations between TL biology and human health over time, leading to effective LTL usage in medical applications.

BackgroundResearch and policy demonstrate the value of and need for systematically identifying and preparing care partners for their caregiving responsibilities while their family member or friend living with dementia is hospitalized. The Care Partner Hospital Assessment Tool (CHAT) has undergone content and face validation and has been endorsed as appropriate by clinicians to facilitate the timely identification and preparation of care partners of older adult patients during their hospitalization. However, the CHAT has not yet been adapted or prospectively evaluated for use with care partners of hospitalized people living with dementia. Adapting and testing the CHAT via a pilot study will provide the necessary evidence to optimize feasibility and enable future efficacy trials. ObjectiveThe purpose of this paper is to describe the study protocol for the adaptation and testing of the CHAT for use among care partners of hospitalized people living with dementia to better prepare them for their caregiving responsibilities after hospital discharge. MethodsOur protocol is based on the National Institutes of Health Stage Model and consists of 2 sequential phases, including formative research and the main trial. In phase 1, we will use a participatory human-centered design process that incorporates people living with dementia and their care partners, health care administrators, and clinicians to adapt the CHAT for dementia care (ie, the Dementia CHAT [D-CHAT]; stage IA). In phase 2, we will partner with a large academic medical system to complete a pilot randomized controlled trial to examine the feasibility and estimate the size of the effect of the D-CHAT on care partners’ preparedness for caregiving (stage IB). We anticipate this study to take approximately 60 months to complete, from study start-up procedures to dissemination. The 2 phases will take place between December 1, 2022, and November 30, 2027. ResultsThe study protocol will yield (1) a converged-upon, ready-for-feasibility testing D-CHAT; (2) descriptive and feasibility characteristics of delivering the D-CHAT; and (3) effect size estimates of the D-CHAT on care partner preparedness. We anticipate that the resultant D-CHAT will provide clinicians with guidance on how to identify and better prepare care partners for hospitalized people living with dementia. In turn, care partners will feel equipped to fulfill caregiving roles for their family members or friends living with dementia. ConclusionsThe expected results of this study are to favorably impact hospital-based care processes and outcomes for people living with dementia and their care partners and to elucidate the essential caregiving role that so many care partners of people living with dementia assume. Trial RegistrationClinicalTrials.gov NCT05592366; https://clinicaltrials.gov/ct2/show/NCT05592366 International Registered Report Identifier (IRRID)PRR1-10.2196/46808

Circulatory system diseases and nervous system disorders often co-occur in patients. Here the authors use eMERGE and UK BioBank data to identify genomic regions associated with both phenotypes, providing insight into the relationship between these conditions.

PurposeDuctal carcinoma in situ (DCIS), is a noninvasive breast cancer, representing 20-25% of breast cancer diagnoses in the USA. Current treatment options for DCIS include mastectomy or breast-conserving surgery (BCS) with or without radiation therapy (RT), but optimal risk-adjusted treatment selection remains a challenge. Findings from past and recent clinical trials have failed to identify a ‘low risk’ group of patients who do not benefit significantly from RT after BCS. To address this unmet need, a DCIS biosignature, DCISionRT (PreludeDx, Laguna Hills, CA), was developed and validated in multiple cohorts. DCISionRT is a molecular assay with an algorithm reporting a recurrence risk score for patients diagnosed with DCIS intended to guide DCIS treatment. In this study, we present results from analytical validity, performance assessment, and clinical performance validation and clinical utility for the DCISionRT test comprised of multianalyte assays with algorithmic analysis.MethodsThe analytical validation of each molecular assay was performed based on the Clinical and Laboratory Standards Institute (CLSI) guidelines Quality Assurance for Design Control and Implementation of Immunohistochemistry Assays and the College of American Pathologists/American Society of Clinical Oncology (CAP/ASCO) recommendations for analytic validation of immunohistochemical assays.ResultsThe analytic validation showed that the molecular assays that are part of DCISionRT test have high sensitivity, specificity, and accuracy/reproducibility (≥95%). The analytic precision of the molecular assays under controlled non-standard conditions had a total standard deviation of 6.6 (100-point scale), where the analytic variables (Lot, Machine, Run) each contributed

Background:. Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused more than 600 million cases and over six million deaths worldwide. Despite the availability of vaccination, COVID-19 cases continue to grow making pharmacological interventions essential. Remdesivir (RDV) is an FDA-approved antiviral drug for treatment of both hospitalized and non-hospitalized COVID-19 patients, albeit with potential for hepatotoxicity. This study characterizes the hepatotoxicity of RDV and its interaction with dexamethasone (DEX), a corticosteroid often co-administered with RDV for inpatient treatment of COVID-19. Methods:. Human primary hepatocytes and HepG2 cells were used as in vitro models for toxicity and drug-drug interaction studies. Real-world data from hospitalized COVID-19 patients were analyzed for drug-induced elevation of serum ALT and AST. Results:. In cultured hepatocytes, RDV markedly reduced the hepatocyte viability and albumin synthesis, while it increased the cleavage of caspase-8 and caspase-3, phosphorylation of histone H2AX, and release of ALT and AST in a concentration-dependent manner. Importantly, co-treatment with DEX partially reversed RDV-induced cytotoxic responses in human hepatocytes. Moreover, data from COVID-19 patients treated with RDV with and without DEX co-treatment suggested that among 1037 patients matched by propensity score, receiving the drug combination was less likely to result in elevation of serum AST and ALT levels (≥ 3 × ULN) compared to the RDV alone treated patients (OR = 0.44, 95% CI = 0.22–0.92, p = 0.03). Conclusion:. Our findings obtained from in vitro cell-based experiments and patient data analysis provide evidence suggesting combination of DEX and RDV holds the potential to reduce the likelihood of RDV-induced liver injury in hospitalized COVID-19 patients.

Measuring the spatial distribution of microparticles which include synthetic, semi-synthetic, and anthropogenic particles is critical to understanding their potential negative impacts on species. This is particularly important in the context of microplastics, which are a form of microparticle that are prevalent in the marine environment. To facilitate a better understanding of microparticle occurrence, including microplastics, we sampled subadult and young juvenile Black Rockfish (Sebastes melanops) at multiple Oregon coast sites, and their gastrointestinal tracts were analyzed to identify ingested microparticles. Of the subadult rockfish, one or more microparticles were found in the GI tract of 93.1% of the fish and were present in fish from Newport, and near four of five marine reserves. In the juveniles, 92% of the fish had ingested one or more microparticles from the area of Cape Foulweather, a comparison area, and Otter Rock, a marine reserve. The subadults had an average of 7.31 (average background = 5) microparticles detected, while the juveniles had 4.21 (average background = 1.8). In both the subadult and juvenile fish, approximately 12% of the microparticles were identified as synthetic using micro-Fourier Infrared Spectroscopy (micro-FTIR). Fibers were the most prevalent morphology identified, and verified microparticle contamination was a complex mixture of synthetic (∼12% for subadults and juveniles), anthropogenic (∼87% for subadults and 85.5% for juveniles), and natural (e.g., fur) materials (∼0.7% for subadults and ∼2.4% for juveniles). Similarities in exposure types (particle morphology, particle number) across life stages, coupled with statistical differences in exposure levels at several locations for subadult fish, suggest the potential influence of nearshore oceanographic patterns on microparticle distribution. A deeper understanding of the impact microplastics have on an important fishery such as those for S. melanops, will contribute to our ability to accurately assess risk to both wildlife and humans.

Maize lethal necrosis is a destructive virus disease of maize caused by maize chlorotic mottle virus (MCMV) in combination with a virus in the family Potyviridae. Emergence of MLN is typically associated with the introduction of MCMV or its vectors and understanding its spread through seed is critical for disease management. Previous studies suggest that although MCMV is detected on seed, the seed transmission rate of this virus is low. However, mechanisms influencing its transmission are poorly understood. Elucidating these mechanisms is crucial for informing strategies to prevent spread on contaminated seed. In this study, we evaluated the rate of MCMV seed transmission using seed collected from plants that were artificially inoculated with MCMV isolates from Hawaii and Kenya. Grow-out tests indicated that MCMV transmission through seed was rare, with a rate of 0.004% among the more than 85,000 seed evaluated, despite detection of MCMV at high levels in the seed lots. To understand factors that limit transmission from seed, MCMV distribution in seed tissues was examined using serology and immunolocalization. The virus was present at high levels in maternal tissues, the pericarp and pedicel, but absent from filial endosperm and embryo seed tissues. The ability to transmit MCMV from seed to uninfected plants was tested to evaluate virus viability. Transmission was negatively associated with both seed maturity and moisture content. Transmission of MCMV from infested seed dried to less than 15% moisture was not detected, suggesting proper handling could be important for minimizing spread of MCMV through seed.