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Abstract Structural diversity (SD) characterizes the volume and physical arrangement of biotic components in an ecosystem which control critical ecosystem functions and processes. LiDAR data provides detailed 3-D spatial position information of components and has been widely used to calculate SD. However, the intensive computation of SD metrics from extensive LiDAR datasets is time-consuming and challenging for researchers who lack access to high-performance computing resources. Moreover, a lack of understanding of LiDAR data and algorithms could lead to inconsistent SD metrics. Here, we developed a SD product using the Discrete-Return LiDAR Point Cloud from the NEON Aerial Observation Platform. This product provides SD metrics detailing height, density, openness, and complexity at a spatial resolution of 30 m, aligned to the Landsat grids, for 211 site-years for 45 Terrestrial NEON sites from 2013 to 2022. To accommodate various ecosystems with different understory heights, it includes three different cut-off heights (0.5 m, 2 m, and 5 m). This structural diversity product can enable various applications such as ecosystem productivity estimation and disturbance monitoring.

Abstract Determining the genetic contributions to Parkinson’s disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study is part of the Global Parkinson’s Genetics Program, supported by the Aligning Science Across Parkinson’s initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.

Abstract Background Direct acting antivirals (DAAs) for the Hepatitis C virus (HCV) have shifted the World Health Organisation global strategic focus to the elimination of HCV by 2030. In England, the UK Health Security Agency (UKHSA) led a national ‘patient re-engagement exercise’, using routine surveillance data, which was delivered through the HCV Operational Delivery Networks (ODNs) with support from National Health Service England (NHSE), to help find and support people with a positive HCV PCR test result to access treatment. We report a quantitative evaluation of outcomes of this exercise. Methods Individuals with a recorded positive HCV antibody or PCR result between 1996 and 2017 were identified using UKHSA’s records of HCV laboratory diagnosis. Linkage with established health-care datasets helped to enhance patient identification and minimise attempts to contact deceased or previously treated individuals. From September to November 2018 each ODN was provided with a local list of diagnosed individuals. ODNs were asked to perform further data quality checks through local systems and then write to each individual’s GP to inform them that the individual would be contacted by the ODN to offer confirmatory HCV PCR testing, assessment and treatment unless the GP advised otherwise. Outcomes of interest were receipt of treatment, a negative PCR result, and death. Data were collected in 2022. Results Of 176,555 individuals with a positive HCV laboratory report, 55,329 individuals were included in the exercise following linkage to healthcare datasets and data reconciliation. Participants in the study had a median age of 51 years (IQR: 43, 59), 36,779 (66.5%) were males, 47,668 (86.2%) were diagnosed before 2016 and 11,148 (20.2%) lived in London. Of the study population, 7,442 (13.4%) had evidence of treatment after the re-engagement exercise commenced, 6,435 (11.6%) were reported as PCR negative (96% had no previous treatment records), 4,195 (7.6%) had prescription data indicating treatment before the exercise commenced or were reported to have been treated previously by their ODN, and 2,990 (5.4%) had died. The status of 32,802 (59.3%) people remains unknown. Conclusions A substantial number of those included had treatment recorded after the exercise commenced, however, many more remain unengaged. Evaluation of the exercise highlighted areas that could be streamlined to improve future exercises.

Abstract Lyme disease, the most prevalent tick‐borne disease in North America, is caused by the bacterium Borrelia burgdorferi, and in the eastern and central United States, it is spread to humans by the black‐legged tick (Ixodes scapularis). Due to the complex, multiyear and multihost life cycle of this species, a matrix modeling approach is needed to effectively estimate subseasonal, multistage survival and transition dynamics in order to better understand and predict when population growth is high. Of the three questing tick life stages (larvae, nymphs, and adults), nymphs are most often associated with transmitting the bacteria to humans, and previous work suggests a mix of abiotic and biotic drivers are associated with nymph abundance. However, understanding tick population growth requires understanding mortality and transition probabilities for each stage and each stage may be individually and uniquely impacted by climate and host availability. A larval tick, for example, may experience warming temperatures differently than nymph or adults, because they are present on the landscape at different times. Here, we describe and validate a model that accounts for field sampling design and evaluates abiotic (temperature, relative humidity, precipitation) and biotic (host abundance) drivers of variation in tick population growth. To account for the drivers of subseasonal and interannual variability in demography, phenology, and population density, we built stage‐structured population models that account for variability in meteorology and host population abundance throughout the full tick lifecycle. Our model is fit and validated with 11 years of tick and host data from the northeastern United States. In this context, we found that a four‐stage model that includes unique transitions to and from a dormant, overwintering nymph state outperforms a model that only includes the three questing stages, and that incorporating the abundance of the predominant host species, Peromyscus leucopus, and weather variables improved predictions and model fit. Additionally, the model accurately predicted all three questing stages at sites different than where they were calibrated, showing that this model structure is generally transferable. Overall, this model lays a foundation for the real‐time iterative forecasting of tick populations needed to effectively protect public health.

Abstract Background Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract

Abstract Anthropogenic activities are causing detrimental changes to coastal plants– namely seagrass, mangrove, and tidal marshes. Looking beyond recent times to past vegetation dynamics is critical to assess the response and resilience of an environment to change. Here, we develop a high-resolution multi-proxy approach, providing a new evidence base to decipher long-term change in coastal plant communities. Combining targeted environmental DNA analysis with chemical analysis of soils, we reconstructed 4,000 years of change at a temperate wetland on Torrens Island South Australia and identified an ecosystem shift that occurred ~ 1000 years ago. What was once a subtidal seagrass system shifted to an intertidal mangrove environment that persists at this site today. We demonstrate that high-resolution historical changes in coastal vegetation can be attained using these proxies. This approach could be applied to other ecosystems to improve the way we protect, conserve, and restore vegetated ecosystems.

Abstract Background Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively. The heparan sulphate cleaving enzyme, heparanase, has previously been shown to contribute to diabetic microvascular complications, but the common underlying mechanism which results in microvascular dysfunction in conditions such as DR and DKD has not been determined. Methods In this study, two mouse models of heparan sulphate depletion (enzymatic removal and genetic ablation by endothelial specific Exotosin-1 knock down) were utilized to investigate the impact of endothelial cell surface (i.e., endothelial glycocalyx) heparan sulphate loss on microvascular barrier function. Endothelial glycocalyx changes were measured using fluorescence microscopy or transmission electron microscopy. To measure the impact on barrier function, we used sodium fluorescein angiography in the eye and a glomerular albumin permeability assay in the kidney. A type 2 diabetic (T2D, db/db) mouse model was used to determine the therapeutic potential of preventing heparan sulphate damage using treatment with a novel heparanase inhibitor, OVZ/HS-1638. Endothelial glycocalyx changes were measured as above, and microvascular barrier function assessed by albumin extravasation in the eye and a glomerular permeability assay in the kidney. Results In both models of heparan sulphate depletion, endothelial glycocalyx depth was reduced and retinal solute flux and glomerular albumin permeability was increased. T2D mice treated with OVZ/HS-1638 had improved endothelial glycocalyx measurements compared to vehicle treated T2D mice and were simultaneously protected from microvascular permeability changes associated with DR and DKD. Conclusion We demonstrate that endothelial glycocalyx heparan sulphate plays a common mechanistic role in microvascular barrier function in the eye and kidney. Protecting the endothelial glycocalyx damage in diabetes, using the novel heparanase inhibitor OVZ/HS-1638, effectively prevents microvascular permeability changes associated with DR and DKD, demonstrating a novel systemic approach to address diabetic microvascular complications.

Abstract Background Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization’s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. Methods This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. Conclusion The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. Study registration This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Abstract Cold‐air pooling is an important topoclimatic process that creates temperature inversions with the coldest air at the lowest elevations. Incomplete understanding of sub‐canopy spatiotemporal cold‐air pooling dynamics and associated ecological impacts hinders predictions and conservation actions related to climate change and cold‐dependent species and functions. To determine if and how cold‐air pooling influences forest composition, we characterized the frequency, strength, and temporal dynamics of cold‐air pooling in the sub‐canopy at local to regional scales in New England, USA. We established a network of 48 plots along elevational transects and continuously measured sub‐canopy air temperatures for 6–10 months (depending on site). We then estimated overstory and understory community temperature preferences by surveying tree composition in each plot and combining these data with known species temperature preferences. We found that cold‐air pooling was frequent (19–43% seasonal occurrences) and that sites with the most frequent inversions displayed inverted forest composition patterns across slopes with more cold‐adapted species, namely conifers, at low instead of high elevations. We also observed both local and regional variability in cold‐air pooling dynamics, revealing that while cold‐air pooling is common, it is also spatially complex. Our study, which uniquely focused on broad spatial and temporal scales, has revealed some rarely reported cold‐air pooling dynamics. For instance, we discovered frequent and strong temperature inversions that occurred across seasons and in some locations were most frequent during the daytime, likely affecting forest composition. Together, our results show that cold‐air pooling is a fundamental ecological process that requires integration into modeling efforts predicting future forest vegetation patterns under climate change, as well as greater consideration for conservation strategies identifying potential climate refugia for cold‐adapted species.

Abstract Understanding stability—whether a community will eventually return to its original state after a perturbation—is a major focus in the study of various complex systems, particularly complex ecosystems. Here, we challenge this focus, showing that short-term dynamics can be a better predictor of outcomes for complex ecosystems. Using random matrix theory, we study how complex ecosystems behave immediately after small perturbations. Our analyses show that many communities are expected to be ‘reactive’, whereby some perturbations will be amplified initially and generate a response that is directly opposite to that predicted by typical stability measures. In particular, we find reactivity is prevalent for complex communities of mixed interactions and for structured communities, which are both expected to be common in nature. Finally, we show that reactivity can be a better predictor of extinction risk than stability, particularly when communities face frequent perturbations, as is increasingly common. Our results suggest that, alongside stability, reactivity is a fundamental measure for assessing ecosystem health.

IntroductionParental presence at the bedside during a stressful pediatric intensive care unit (PICU) admission may improve child comfort, reduce parental anxiety, and enable family engagement. We performed this study to identify factors that parents perceive impact their capability, opportunity, and motivation to be at the bedside in PICU.MethodsWe conducted a qualitative descriptive study using semi-structured interviews based on the Theoretical Domains Framework (TDF). We included parents of children admitted to the PICU for at least 24 h at IWK Health in Nova Scotia, Canada. Interviews were coded independently by two researchers using a directed content approach based on the TDF. We generated themes and subthemes, with the subthemes identified as factors impacting parental presence, and assigned TDF domains to each of the subthemes.ResultsFourteen primary caregivers (8 mother figures, 6 father figures) participated in 11 interviews. The factors associated with parental presence were captured by 6 themes: Understanding the Medicalized Child; Maintaining the Parent Role; Life Beyond the Hospital; Parental Intrinsic Responses and Coping; Support Structures; and The PICU Environment. Fifty-two barriers and enablers were identified within 13 TDF domains; 10 TDF domains were determined to be relevant to parental presence, which may be used to guide design of future interventions. Participants emphasized the importance of self-care to enable them to remain physically at their child's bedside and to be engaged in their care.ConclusionsParents perceive multiple factors within 6 themes act as barriers or enablers to presence with their critically ill child in the PICU. Guided by relevant TDF domains, interventions may be designed to optimize presence, particularly engaged presence, which may improve health-related outcomes of children and their parents.

BackgroundAlthough goal setting and goal management (GSGM) is a key component of chronic disease management and rehabilitation practice, there is currently no widely used evidence-based intervention system available. This paper describes the theoretical underpinnings and development of a new intervention called MyGoals. MyGoals is designed to guide occupational therapy (OT) practitioners to implement theory-based, client-engaged GSGM for adults with chronic conditions in community-based OT rehabilitation settings.MethodsWe first developed a planning team with two adults with chronic conditions, two clinicians, and two researchers. As a collaborative team, we co-developed MyGoals by following Intervention Mapping (IM) steps 1–4 and incorporating community-based participatory research principles to ensure equitable, ecologically valid, and effective intervention development. In the first step, the planning team conducted a discussion-based needs assessment and a systematic review of current GSGM practice to develop a logic model of the problem. In the second step, the planning team identified performance objectives, intervention target personal determinants, and change objectives, and created a logic model of change and matrics of change objectives. In the third step, the planning team designed MyGoals. Lastly, in the fourth step, the planning team produced, pilot-tested, and refined MyGoals.ResultsThe ultimate goal of the MyGoals intervention is to enable clients to achieve personally meaningful rehabilitation goals. The planning team identified four target determinants (e.g., self-efficacy), six intervention activities (e.g., Education, Reflection, Find My Goals, Make My Goals, Make My Plans, My Progress), eight performance objectives (e.g., List potential goals), and 26 change objectives (e.g., Understand the importance of GSGM). Two pilot tests indicated that MyGoals is feasible for clients and identified areas for improvement. Based on the feedback, minor refinements were made to the MyGoals intervention materials.ConclusionsWe completed rigorous and collaborative IM to develop MyGoals. Establishing the theoretical and developmental foundation for MyGoals sets the groundwork for high-quality, evidence-based GSGM. Future studies on effectiveness and implementation are necessary to refine, translate, and scale MyGoals in rehabilitation practice.

Abstract 3D printing has emerged as a powerful way to produce complex materials on‐demand. These printing technologies are now being applied in microbiology, with many recent examples where microbes and matrices are co‐printed to create bespoke living materials. Here, we propose a new paradigm for microbial printing. In addition to its importance for materials, we argue that printing can be used to understand and engineer microbiome communities, analogous to its use in human tissue engineering. Many microbes naturally live in diverse, spatially structured communities that are challenging to study and manipulate. 3D printing offers an exciting new solution to these challenges, as it can precisely arrange microbes in 3D space, allowing one to build custom microbial communities for a wide range of purposes in research, medicine, and industry.

CONTEXT:. PICUs across Canada restricted family presence (RFP) in response to the COVID-19 pandemic from allowing two or more family members to often only one family member at the bedside. The objective of this study was to describe the experiences and impact of RFP on families of critically ill children to inform future policy and practice. HYPOTHESIS:. RFP policies negatively impacted families of PICU patients and caused moral distress. METHODS AND MODELS:. National, cross-sectional, online, self-administered survey. Family members of children admitted to a Canadian PICU between March 2020 and February 2021 were invited to complete the survey. RFP-attributable distress was measured with a modified distress thermometer (0–10). Closed-ended questions were reported with descriptive statistics and multivariable linear regression assessed factors associated with RFP-attributable distress. Open-ended questions were analyzed using inductive content analysis. RESULTS:. Of 250 respondents who experienced RFP, 124 (49.6%) were restricted to one family member at the bedside. The median amount of distress that families attributed to RFP policies was 6 (range: 0–10). Families described isolation, removal of supports, and perception of trauma related to RFP. Most families (183, 73.2%) felt that policies were enforced in a way that made them feel valued by PICU clinicians, which was associated with less RFP-attributable distress. Differential impact was seen where families with lower household income indicated higher RFP-attributable distress score (2.35; 95% CI, 0.53–4.17; p = 0.03). Most respondents suggested that future policies should allow at least two family members at the bedside. INTERPRETATIONS AND CONCLUSIONS:. Families of children admitted to PICUs during the COVID-19 pandemic described increased distress, trauma, and removal of supports due to RFP policies. Vulnerable families showed an increased odds of higher distress. Healthcare professionals played an important role in mitigating distress. Allowance of at least two family members at the bedside should be considered for future policy.

Abstract Changes in vegetation in North America indicate Holocene shifts in the latitudinal temperature gradient along the western margin of the North Atlantic. Tree taxa such as oak (Quercus) and birch (Betula) experienced opposing directions of change across different latitudes consistent with changes in temperature gradient steepness. Pollen‐inferred temperatures from 34 sites quantify the gradient changes and reconstruct a long‐term northward steepening in summer and southward steepening in winter. From 4.8 to 3.8 ka, an oscillation in tree distributions interrupted the long‐term trends as a steep temperature gradient developed north of 43.5°N. The shift likely limited cold outbreaks to the south, producing anomalously high summer temperatures at 42–43.5°N, and enabling a northward expansion of oak forests. The forest and temperature gradient changes appear consistent with orbital and ice sheet forcing as well as millennial variability in the North Atlantic pressure field analogous to the North Atlantic Oscillation on interannual time scales.

Introduction: In 2015, a centralized Multi-Specialist Telemedicine (TM) Consultation Program was established to improve access to specialist care and enhance continuity of care for homebound older adults in Toronto, Canada. Community-dwelling patients were referred to the program by their primary care providers (PCP), treating specialists, and inpatient physicians for specialist-led post-hospital discharge follow-up care. A clinical nurse specialist (CNS) thereafter collaborated with hospital-based consulting specialists, utilizing videoconferencing technology to facilitate consultations and follow-up visits for homebound patients. Methods: We conducted a retrospective observational study of the overall intervention including patient characteristics and the number/type of consultations provided by analyzing the clinical charts of each enrolled patient. Satisfaction surveys were conducted after five years of program implementation with patients, family caregivers and healthcare providers utilizing paper-based questionnaires administered by members of our research team. Data were analyzed using summary statistics. Results: From April 2015 to March 2020, this program supported a total of 216 homebound patients, with an average age of 84 years, and an average Charlson Comorbidity Index (CCI) of 3.36. Patients received a total of 1,003 consultation and follow-up visits from 42 specialist care providers representing 22 unique clinical specialties. 59 (27%) patients and family caregivers and 22 specialist and primary care providers voluntarily completed satisfaction surveys. 100% of surveyed patients and caregivers reported being very satisfied with the program and 86% of physicians reported that the program enhanced their delivery of patient care. Conclusion: Our TM program had a high participation rate and showed promising results in improving the delivery of patient care by centrally facilitating multi-specialist consultations and maintaining continuity of care for homebound older adults in an urban setting, which may have potentially reduced future ED visits. The program also received high satisfaction rates among providers, patients, and caregivers, indicating a positive response to its implementation.

A Monte-Carlo based computational approach for the statistical characterization of the whole-body specific absorption rate (wbSAR) variability in large cohorts of rodents exposed to radio-frequency (RF) energy in reverberation chambers (RCs) is applied to adult male rat exposures illustrative of those in a US National Toxicology Program (NTP) cancer bioassay. A large number of 3D electromagnetic field realizations fulfilling Rayleigh fading properties were generated within an electrically-large volume representative of an ideal RC, yielding granular wbSAR distributions for an ensemble of 96 homogeneous rodent models with random mass distribution, postures, positions and orientations. Two case studies were addressed: a “momentary exposure” with each rat fixed in posture, position and orientation, and a “day-long exposure” in which the position, orientation and posture were varied randomly for each subsequent Rayleigh field realization. Over 500 and 2500 field realizations or “snapshots”, respectively, the rats’ instantaneous wbSARs, as well as their individual time-averaged wbSARs, were found to be well fit by lognormal distributions. The large variability in instantaneous wbSARs in the cohort was due in part to the inherent Rayleigh field variability in RCs (70-80%) and in part to weight, posture and position variations (20-30%), while the effect of cage location was found to be small over day-long exposures. Averaging the exposure over field realizations substantially reduces the range of wbSARs in the cohort. Hence, when RF-induced thermal effects are studied, the relevant exposure metric (wbSAR averaged over appropriate times) features a narrower range than instantaneous wbSAR, which is the relevant metric in studies dealing with non-thermal effects. Compared to previous studies, the present approach was found to be computationally more efficient enabling thus a Monte-Carlo analysis by varying concurrently the incident field and the animals posture, position, and orientation. In practice, it can inform the choice of wbSAR targets in rodent bioassay, allowing to identify possible dose-effect trends while avoiding undue thermal stress.

Bacteria respond to nutrients and other compounds via chemotaxis, but little is known of their responses to antibiotics. By tracking cells in antibiotic gradients, the authors show that surface-attached Pseudomonas aeruginosa move towards antibiotics in what appears to be a suicidal attack strategy.

We describe a microvertebrate assemblage from the J&M site, of the Upper Cretaceous (Campanian–Maastrichtian) Williams Fork Formation. Breakdown of fossil bearing matrix was achieved with the use of heated dimethyl sulfoxide. Nine of the recovered taxa are new to both the J&M site and the Williams Fork Formation. The sharks Lonchidion griffisi, Chiloscyllium sp., and Cantioscyllium markaguntensis are the first non-batoid elasmobranchs reported from the Williams Fork Formation and are all represented by teeth. The rays Cristomylus and Psuedomyledaphus are also newly reported from teeth. The most common identifiable fossils were teeth of indeterminate amiids, most likely belonging to Melvius. Osteichthyan fossils new to the Williams Fork Formation include teeth of Paralbula, an indeterminate pycnodontid tooth plate fragment, and an indeterminate lungfish tooth fragment. A tooth of the teiid Peneteius is also the first reported from within the Williams Fork Formation. Alligatoroid teeth are relatively common and are extremely similar to those of the contemporaneous durophage Brachychampsa but are generically indeterminate. Terrestrial taxa were recovered in much smaller numbers. Theropod dinosaur fossils included isolated tooth fragments belonging to an indeterminate dromaeosaurid and, possibly, to Richardoestesia. We recovered both multituberculate and metatherian fossils in the form of isolated teeth. Some of these taxa are known from marine and estuarine deposits and, given that so many of these marine associated taxa have been recovered together, it seems likely that the J&M site is recording marine or estuarine influence within at least part of its depositional history. The mammalian taxa suggest a Judithian–Lancian age for the site, while records of the squamate Peneteius and the ray Myledaphus, suggest that the J&M site may be temporally transitional between other late Campanian and late Maastrichtian-aged localities.

Recent X-ray studies of starburst galaxies have found that charge exchange (CX) commonly occurs between outflowing hot plasma and cold gas, possibly from swept-up clouds. However, the total CX flux and the regions where CX occurs have been poorly understood. We present an analysis of XMM-Newton observations of M82, a prototype starburst galaxy, aiming to investigate these key properties of CX emission. We have used a blind source separation method in an image analysis of CCD data, which identified a component with the enhanced O–K lines expected from the CX process. Analyzing the XMM-Newton/RGS spectra from the regions identified by the image analysis, we have detected a high forbidden-to-resonance ratio of the O vii He α triplet as well as several emission lines from K-shell transitions of C, N, and O that are enhanced by the CX process. CX is less responsible for the emission lines of Ne and Mg, and accurate estimation of the CX contribution is confirmed to be crucial in measuring chemical abundances. The temperature of the plasma acting as an electron receiver in the CX process is significantly lower compared to that of the plasma components responsible for most of the X-rays. From the low temperature and an estimation of the CX-emitting volume, we find that the CX primarily occurs in a limited region at interfaces between plasma and gas whose temperatures rapidly decrease due to thermal conduction.

Accurate atomic data and plasma models are essential for interpreting the upcoming high-quality spectra from missions like XRISM and Athena. Estimating physical quantities, like temperature, abundance, turbulence, and the resonance scattering factor, is highly dependent on the underlying atomic data. We use the AtomDB tool variableapec to estimate the impact of atomic data uncertainties in Einstein A coefficients, collisional rate coefficients, and the ionization and recombination rates of H-, He-, and Li-like iron in modeling the spectrum of Perseus observed by Hitomi. The best-fit temperatures, abundances, resonance scattering factors, and turbulence parameters including atomic data uncertainties vary by approximately 17%, 35%, 30%, and 3%, respectively, from the best-fit temperatures, abundances, RS factors, and turbulence parameters estimated without atomic data uncertainties. These indicate that approximately 32%, 35%, and 25% of the best-fit temperatures, abundances, and resonance scattering factors when including uncertainties lie outside the 3 σ error regions of their corresponding best-fit values computed with zero atomic data errors. Expanding the energy range to 1.8–20.0 keV shows less variability, with 26% of the abundances and 22% of the resonance scattering factors lying outside the 3 σ errors of the best-fit values. We also studied correlations between physical parameters and atomic rate uncertainties to identify key atomic quantities requiring precise lab measurements. We report negative correlations between the best-fit temperatures and the z (1s2s ^3 S _1 → 1s ^2 ) collisional rate coefficients, abundances and y (1s2p ^3 P _1 → 1s ^2 ) collisional rate coefficients, and abundances and z collisional rate coefficients, and a positive correlation between the resonance scattering factors and the w (1s2p ^1 P _1 → 1s ^2 ) collisional rate coefficients.

Abstract The majority of ecological, industrial and medical impacts of bacteria result from diverse communities containing multiple species. This diversity presents a significant challenge as co-cultivation of multiple bacterial species frequently leads to species being outcompeted and, with this, the possibility to manipulate, evolve and improve bacterial communities is lost. Ecological theory predicts that a solution to this problem will be to grow species in structured environments, which reduces the likelihood of competitive exclusion. Here, we explored the ability of cultivation in a structured environment to facilitate coexistence, evolution, and adaptation in an industrially important community: Lactococcus lactis and Leuconostoc mesenteroides frequently used as dairy starter cultures. As commonly occurs, passaging of these two species together in a liquid culture model led to the loss of one species in 6 of 20 lineages (30%). By contrast, when we co-cultured the two species as biofilms on beads, a stable coexistence was observed in all lineages studied for over 100 generations. Moreover, we show that the co-culture drove evolution of new high-yield variants, which compared to the ancestor grew more slowly, yielded more cells and had enhanced capability of biofilm formation. Importantly, we also show that these high-yield biofilm strains did not evolve when each species was passaged in monoculture in the biofilm model. Therefore, both co-culture and the biofilm model were conditional for these high-yield strains to evolve. Our study underlines the power of ecological thinking—namely, the importance of structured environments for coexistence—to facilitate cultivation, evolution, and adaptation of industrially important bacterial communities.

Humans, and many other species, carry a large set of beneficial microbes. Here, the authors present new theory and data to argue that these vital relationships only work when hosts can control their microbiome and suppress wayward symbionts.

The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier. Previously, we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. In this study, we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action. Streptozotocin-induced diabetic Wistar rats developed albuminuria, increased glomerular albumin permeability (Ps’alb), and increased glomerular matrix metalloproteinase (MMP) activity with corresponding GEnGlx loss. MR antagonism prevented albuminuria progression, restored Ps’alb, preserved GEnGlx, and reduced MMP activity. Enzymatic degradation of the GEnGlx negated the benefits of MR antagonism, confirming their dependence on GEnGlx integrity. Exposing human glomerular endothelial cells (GEnC) to diabetic conditions in vitro increased MMPs and caused glycocalyx damage. Amelioration of these effects confirmed a direct effect of MR antagonism on GEnC. To confirm relevance to human disease, we used a potentially novel confocal imaging method to show loss of GEnGlx in renal biopsy specimens from patients with diabetic nephropathy (DN). In addition, patients with DN randomized to receive an MR antagonist had reduced urinary MMP2 activity and albuminuria compared with placebo and baseline levels. Taken together, our work suggests that MR antagonists reduce MMP activity and thereby preserve GEnGlx, resulting in reduced glomerular permeability and albuminuria in diabetes.

Summary: Genetically identical bacterial cells commonly display different phenotypes. This phenotypic heterogeneity is well known for stress responses, where it is often explained as bet hedging against unpredictable environmental threats. Here, we explore phenotypic heterogeneity in a major stress response of Escherichia coli and find it has a fundamentally different basis. We characterize the response of cells exposed to hydrogen peroxide (H2O2) stress in a microfluidic device under constant growth conditions. A machine-learning model reveals that phenotypic heterogeneity arises from a precise and rapid feedback between each cell and its immediate environment. Moreover, we find that the heterogeneity rests upon cell-cell interaction, whereby cells shield each other from H2O2 via their individual stress responses. Our work shows how phenotypic heterogeneity in bacterial stress responses can emerge from short-range cell-cell interactions and result in a collective phenotype that protects a large proportion of the population.

Abstract Background People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes. Methods We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD). Results The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50–59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages. Conclusions We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.

Abstract A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of the COVID-19 pandemic that originated in China in December 2019. Although extensive research has been performed on SARS-CoV-2, the binding behavior of spike (S) protein and receptor binding domain (RBD) of SARS-CoV-2 at different environmental conditions have yet to be studied. The objective of this study is to investigate the effect of temperature, fatty acids, ions, and protein concentration on the binding behavior and rates of association and dissociation between the S protein and RBD of SARS-CoV-2 and the hydrophobic aminopropylsilane (APS) biosensors using biolayer interferometry (BLI) validated with molecular dynamics simulation. Our results suggest three conditions—high ionic concentration, presence of hydrophobic fatty acids, and low temperature—favor the attachment of S protein and RBD to hydrophobic surfaces. Increasing the temperature within an hour from 0 to 25 °C results in S protein detachment, suggesting that freezing can cause structural changes in the S protein, affecting its binding kinetics at higher temperature. At all the conditions, RBD exhibits lower dissociation capabilities than the full-length S trimer protein, indicating that the separated RBD formed stronger attachment to hydrophobic surfaces compared to when it was included in the S protein.

A campaign is underway to clear established forests and expand early-successional habitats—also called young forest, pre-forest, early seral, or open habitats—with the intention of benefitting specific species. Coordinated by federal and state wildlife agencies, and funded with public money, public land managers work closely with hunting and forestry interests, conservation organizations, land trusts, and private landowners toward this goal. While forest-clearing has become a major focus in the Northeast and Upper Great Lakes regions of the U.S., far less attention is given to protecting and recovering old-forest ecosystems, the dominant land cover in these regions before European settlement. Herein we provide a discussion of early-successional habitat programs and policies in terms of their origins, in the context of historical baselines, with respect to species’ ranges and abundance, and as they relate to carbon accumulation and ecosystem integrity. Taken together, and in the face of urgent global crises in climate, biodiversity, and human health, we conclude that public land forest and wildlife management programs must be reevaluated to balance the prioritization and funding of early-successional habitat with strong and lasting protection for old-growth and mature forests, and, going forward, must ensure far more robust, unbiased, and ongoing monitoring and evaluation.

Abstract Background An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. Methods We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. Results We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39–1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49–0.76) and ischaemic stroke (HR = 0.27, CI 0.08–0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results. Conclusion We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on ‘patients like me’. We identify the key challenges in offering such an Informatics Consult as a service.

Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response.

The burden of mental illness in young people with chronic liver disease is not known. In this population cohort study in England, we identified 358 individuals (aged ≤25 years) diagnosed with autoimmune hepatitis or liver disease related to cystic fibrosis and 1541 propensity-score-matched controls. By the first year of follow-up, the cumulative burden of psychiatric events in participants with liver disease was high compared with controls: anxiety disorder (6.87 per 100 individuals [95% CI 4.00–9.73] v. 2.22 [95% CI 1.37–3.07]), depression (5.10 [95% CI 2.83–7.37] v. 0.86 [95% CI 0.53–1.19]), substance misuse (10.61 [95% CI 9.50–11.73] v. 1.23 [95% CI 0.71–1.75]) and self-harm (3.09 [95% CI 1.12–5.05] v. 0.20 [95% CI 0.07–0.33]). Participants with liver disease had a 2-fold increase (OR = 1.94, 95% CI 1.45–2.58), a 2.5-fold increase (OR = 2.59, 95% CI 1.91–3.50) and 4.4-fold increase (OR = 4.44; 95% CI 3.46–5.71) in the risk of anxiety, depression and substance misuse, respectively. These findings highlight the need for effective intervention in psychiatric disorders in young people with rare liver disease.

Abstract Recent expansion in data sharing has created unprecedented opportunities to explore structure–function linkages in ecosystems across spatial and temporal scales. However, characteristics of the same data product, such as resolution, can change over time or spatial locations, as protocols are adapted to new technology or conditions, which may impact the data's potential utility and accuracy for addressing end user scientific questions. The National Ecological Observatory Network (NEON) provides data products for users from 81 sites and over a planned 30‐year time frame, including discrete‐return light detection and ranging (LiDAR) from an airborne observation platform. LiDAR is a well‐established and increasingly available remote sensing technology for measuring three‐dimensional characteristics of ecosystem and landscape structure, including forest structural diversity. The LiDAR product that NEON provides can vary in point density from 2 to 25+ pt/m2 depending on the instrument and acquisition date. We used NEON LiDAR from five forested sites to (1) identify the minimum point density at which structural diversity metrics can be robustly estimated across forested sites from different ecoclimatic zones in the United States and (2) to test the effects of variable point density on the estimation of a suite of structural diversity metrics and multivariate structural complexity types within and across forested sites. Twelve of 16 structural diversity metrics were sensitive to LiDAR point density in at least one of the five NEON forested sites. The minimum point density to reliably estimate the metrics ranged from 2.0 to 7.5 pt/m2, but our results indicate that point densities above 7–8 pt/m2 should provide robust measurements of structural diversity in forests for temporal or spatial comparisons. The delineation of multivariate structural complexity types from a suite of 16 structural diversity metrics was robust within sites and across forest types for a LiDAR point density of 4 pt/m2 and above. This study shows that different metrics of structural diversity can vary in their sensitivity to the resolution of LiDAR data and that users of these open‐source data products should consider the point density of their data and use caution in metric selection when making spatial or temporal comparisons from these datasets.

Abstract Objective To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes. Methods We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, “Motor Only,” “Psychiatric & Motor,” and “Cognitive & Motor,” which differed in dementia and mortality rates. Parkinson disease participants (“Motor Only”: n = 61, “Psychiatric & Motor”: n = 17, “Cognitive & Motor”: n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow‐up = 4.6 years). Hierarchical linear modeling examined group differences in symptom progression. A three‐way interaction among time, group, and symptom duration (or baseline age, separately) was incorporated to examine disease stages. Results All three subtypes increased in motor dysfunction compared to controls. The “Motor Only” subtype did not show significant cognitive or psychiatric changes compared to the other two subtypes. The “Cognitive & Motor” subtype’s cognitive dysfunction at baseline further declined compared to the other two subtypes, while also increasing in psychiatric symptoms. The “Psychiatric & Motor” subtype’s elevated psychiatric symptoms at baseline remained steady or improved over time, with mild, steady decline in cognition. The pattern of behavioral changes and analyses for disease staging yielded no evidence for sequential disease stages. Interpretation Parkinson disease clinical subtypes progress in clear, temporally distinct patterns from one another, particularly in cognitive and psychiatric features. This highlights the importance of comprehensive clinical examinations as the order of symptom presentation impacts clinical prognosis.

Telomeres suppress the DNA damage response at chromosome ends. Here the authors show that in budding yeast the activity of the MRX complex in DNA repair and DNA damage signaling is inhibited by telomeric protein Rif2 via a short motif at the N-terminus.

This paleoenvironmental database features postglacial lake-sediment records from 31 study sites located across New England. The study sites span an environmental gradient from the cooler, northern and inland part of the region to the warmer, southern and coastal areas of New England. Sediment-core chronologies were determined using 14C dating, 210Pb analysis, and pollen evidence. Detailed analyses of sediment lithology, pollen, and charcoal were used to reconstruct changes in climate, vegetation, and fire at centennial temporal scales and subregional spatial scales for the last 14,000 years. Analyses of paleoenvironmental data provide insights into the rates, patterns, and drivers of ecosystem change, helping us anticipate future ecosystem dynamics and guiding present-day conservation strategies and land management.

Pyruvate kinase (PK) and the phosphoenolpyruvate (PEP) cycle play key roles in nutrient-stimulated KATP channel closure and insulin secretion. To identify the PK isoforms involved, we generated mice lacking β-cell PKm1, PKm2, and mitochondrial PEP carboxykinase (PCK2) that generates mitochondrial PEP. Glucose metabolism was found to generate both glycolytic and mitochondrially derived PEP, which triggers KATP closure through local PKm1 and PKm2 signaling at the plasma membrane. Amino acids, which generate mitochondrial PEP without producing glycolytic fructose 1,6-bisphosphate to allosterically activate PKm2, signal through PKm1 to raise ATP/ADP, close KATP channels, and stimulate insulin secretion. Raising cytosolic ATP/ADP with amino acids is insufficient to close KATP channels in the absence of PK activity or PCK2, indicating that KATP channels are primarily regulated by PEP that provides ATP via plasma membrane-associated PK, rather than mitochondrially derived ATP. Following membrane depolarization, the PEP cycle is involved in an ‘off-switch’ that facilitates KATP channel reopening and Ca2+ extrusion, as shown by PK activation experiments and β-cell PCK2 deletion, which prolongs Ca2+ oscillations and increases insulin secretion. In conclusion, the differential response of PKm1 and PKm2 to the glycolytic and mitochondrial sources of PEP influences the β-cell nutrient response, and controls the oscillatory cycle regulating insulin secretion.

The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.

The spatial arrangement of bacterial strains and species within microbial communities is considered crucial for their ecology. Here, Krishna Kumar et al. use a droplet-based printing method to arrange different bacterial genotypes across a sub-millimetre array, and show that micron-scale changes in spatial distributions can drive major shifts in ecology.

Background & Aims: Despite recent advances in antiviral therapy for hepatitis C virus (HCV), a proportion of patients with genotype 3 (G3) HCV infection do not respond to current all oral treatment regimens. Genomic analyses have identified key polymorphisms correlating with increased resistance to direct-acting antivirals. We previously reported that amino the acid polymorphism, A150V, in the polymerase (NS5B) of G3 HCV reduces response to sofosbuvir. We now demonstrate that this polymorphism alters the response to interferon alpha. Methods: Quantitative polymerase chain reaction, immunofluorescence, luciferase activity assay, immunoblotting, and flow cytometry were used to study the antiviral effect of interferon (IFN) on DBN G3 HCV-infected cells and G3 HCV replicons. Results: We show the presence of the A150V polymorphism markedly reduces the response to IFN alpha (IC50 of S52_WT = 1.162 IU/mL and IC50 of S52_A150V = 14.45 IU/mL, 12.4-fold difference). The induction of IFN-stimulated genes in A150V replicon cells is unaffected, but nuclear localization of active protein kinase R (PKR) is reduced. Blockade of PKR activity reduced the antiviral effect of IFN on wild-type replicons, whereas augmented PKR activation promoted the antiviral effect of IFN on A150V replicons. Furthermore, we show that impaired activation of PKR in A150V replicon cells diminishes cellular apoptosis. Conclusions: These results demonstrate that polymorphisms reducing response rates to direct-acting antivirals may function beyond conferring drug resistance by modulating the intrinsic cellular antiviral response.

Insulin secretion from pancreatic β cells is essential for glucose homeostasis. An insufficient response to the demand for insulin results in diabetes. We previously showed that β cell–specific deletion of Zfp148 (β-Zfp148KO) improves glucose tolerance and insulin secretion in mice. Here, we performed Ca2+ imaging of islets from β‑Zfp148KO and control mice fed both a chow and a Western-style diet. β-Zfp148KO islets demonstrated improved sensitivity and sustained Ca2+ oscillations in response to elevated glucose levels. β-Zfp148KO islets also exhibited elevated sensitivity to amino acid–induced Ca2+ influx under low glucose conditions, suggesting enhanced mitochondrial phosphoenolpyruvate-dependent (PEP-dependent), ATP-sensitive K+ channel closure, independent of glycolysis. RNA-Seq and proteomics of β-Zfp148KO islets revealed altered levels of enzymes involved in amino acid metabolism (specifically, SLC3A2, SLC7A8, GLS, GLS2, PSPH, PHGDH, and PSAT1) and intermediary metabolism (namely, GOT1 and PCK2), consistent with altered PEP cycling. In agreement with this, β-Zfp148KO islets displayed enhanced insulin secretion in response to l-glutamine and activation of glutamate dehydrogenase. Understanding pathways controlled by ZFP148 may provide promising strategies for improving β cell function that are robust to the metabolic challenge imposed by a Western diet.

AimsThis study aims to identify implementation determinants, mechanisms of action, implementation strategies, and implementation outcome evaluation plans for a new theory-based rehabilitation goal setting and goal management intervention system, called MyGoals, using Implementation Mapping with community-based participatory research principles.MethodsWe completed Implementation Mapping tasks 1 to 4 as a planning team consisting of MyGoals target implementers (occupational therapists (OTs), MyGoals intervention target clients (adults with chronic conditions), and the research team. We are currently conducting mapping task 5. These processes were guided by the Consolidated Framework for Implementation Research, social cognitive theory, the taxonomy of behavior change methods, and Proctor's implementation research framework.ResultsWe identified intervention-level determinants (MyGoals' evidence strength & quality, relative advantages) and OT-level determinants (knowledge, awareness, skills, self-efficacy, outcome expectancy). We selected the MyGoals implementation outcome (OTs will deliver MyGoals completely and competently), outcome variables (acceptability, appropriateness, feasibility, fidelity), and process outcomes. We also determined three performance objectives (e.g., OTs will deliver all MyGoals intervention components) and 15 change objectives (e.g., OTs will demonstrate skills for delivering all MyGoals intervention components). Based on the identified outcomes, objectives, and determinants, we specified the mechanisms of change (e.g., active learning). To address these determinants and achieve the implementation outcomes, we produced two tailored MyGoals implementation strategies: MyGoals Clinician Education and MyGoals Clinician Audit & Feedback. We developed evaluation plans to explore and evaluate how these two MyGoals implementation strategies perform using a mixed-methods study of OT-client dyads.ConclusionWe produced tailored implementation strategies for a rehabilitation goal setting and goal management intervention by using Implementation Mapping with community-based participatory research principles. The MyGoals implementation strategies may help OTs implement high-quality goal setting and goal management practice and thus contribute to bridging current research-practice gaps. Our findings can provide insight on how to apply implementation science in rehabilitation to improve the development and translation of evidence-based interventions to enhance health in adults with chronic conditions.

Abstract Spruce–fir (Picea–Abies) forests of the North American Acadian Forest Region are at risk of disappearing from the northeastern United States and Canada due to climate change. Species distribution models (SDMs) have been used to predict changes in this critical transitional ecosystem in the past, but none have addressed how seasonal patterns of temperature and precipitation interact to influence tree species abundance. Inferences have also been limited by contemporary inventory data that could not fully characterize species ranges because they either, (1) only sampled species occurrence after large‐scale human disturbance and settlement, or (2) did not span critical geopolitical boundaries (e.g., the US–Canadian border) that intersect the focal species' range(s). Here, we built new SDM models to better assess the bioclimatic distribution of four spruce–fir species and to test the importance of seasonal climate interactions. We compiled an extensive database of tree occurrence and abundance from recent (~1955–2012) and historical time periods (1623–1869) to model current species distributions and to predict how these might change under future climate. We found that including historical tree data in our SDMs revealed previously unrecognized suitable habitat along the southern edge of species' contemporary ranges. Random forest models predicted occurrence with high accuracy (area under receiver operator curve >0.98), and the seasonal climate variables that emerged as most important for these cold‐adapted species all included interactions that reflected sensitivity to colder temperatures, and preferences for wet weather concentrated in the winter months. Under moderate climate warming (representative concentration pathway 6.0), the northeastern United States retained additional suitable habitat when historical data were included through 2060 for three of the four species: red spruce (Picea rubens), black spruce (Picea mariana), and balsam fir (Abies balsamea), while white spruce (Picea glauca) habitat contracted into Canada. In contrast, future predictions from models that used contemporary data alone forecast extirpation for all four species from the northeastern United States. Overall, these findings highlight that prediction of species ranges in transitional ecosystems that span geopolitical boundaries and gradients of intense land use are improved when historical data and seasonal climate interactions of both temperature and precipitation variables are incorporated.

Abstract Metabarcoding has improved the way we understand plants within our environment, from their ecology and conservation to invasive species management. The notion of identifying plant taxa within environmental samples relies on the ability to match unknown sequences to known reference libraries. Without comprehensive reference databases, species can go undetected or be incorrectly assigned, leading to false‐positive and false‐negative detections. To improve our ability to generate reference sequence databases, we developed a targeted capture approach using the OZBaits_CP V1.0 set, designed to capture chloroplast gene regions across the entirety of flowering plant diversity. We focused on generating a reference database for coastal temperate plant species given the lack of reference sequences for these taxa. Our approach was successful across all specimens with a target gene recovery rate of 92%, which was achieved in a single assay (i.e., samples were pooled), thus making this approach much faster and more efficient than standard barcoding. Further testing of this database highlighted 80% of all samples could be discriminated to family level across all gene regions with some genes achieving greater resolution than others—which was also dependent on the taxon of interest. Thus, we demonstrate the importance of generating reference sequences across multiple chloroplast gene regions as no single loci are sufficient to discriminate across all plant groups. The targeted capture approach outlined in this study provides a way forward to achieve this.