Co-located ecological data for exploring top- and subsoil carbon dynamics across grassland-woodland contrasts.

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0-1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5-15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567).

Clinical and economic outcomes of assigning percutaneous coronary intervention patients to contrast-sparing strategies based on the predicted risk of contrast-induced acute kidney injury.

OBJECTIVE: Contrast-sparing strategies have been developed for percutaneous coronary intervention (PCI) patients at increased risk of contrast-induced acute kidney injury (CI-AKI), and numerous CI-AKI risk prediction models have been created. However, the potential clinical and economic consequences of using predicted CI-AKI risk thresholds for assigning patients to contrast-sparing regimens have not been evaluated. We estimated the clinical and economic consequences of alternative CI-AKI risk thresholds for assigning Medicare PCI patients to contrast-sparing strategies. METHODS: Medicare data were used to identify inpatient PCI from January 2017 to June 2021. A prediction model was developed to assign each patient a predicted probability of CI-AKI. Multivariable modeling was used to assign each patient two marginal predicted values for each of several clinical and economic outcomes based on (1) their underlying clinical and procedural characteristics plus their true CI-AKI status in the data and (2) their characteristics plus their counterfactual CI-AKI status. Specifically, CI-AKI patients above the predicted risk threshold for contrast-sparing were reassigned their no CI-AKI (counterfactual) outcomes. Expected event rates, resource use, and costs were estimated before and after those CI-AKI patients were reassigned their counterfactual outcomes. This entailed bootstrapped sampling of the full cohort. RESULTS: Of the 542,813 patients in the study cohort, 5,802 (1.1%) had CI-AKI. The area under the receiver operating characteristic curve for the prediction model was 0.81. At a predicted risk threshold for CI-AKI of >2%, approximately 18.0% of PCI patients were assigned to contrast-sparing strategies, resulting in (/100,000 PCI patients) 121 fewer deaths, 58 fewer myocardial infarction readmissions, 4,303 fewer PCI hospital days, $11.3 million PCI cost savings, and $25.8 million total one-year cost savings, versus no contrast-sparing strategies. LIMITATIONS: Claims data may not fully capture disease burden and are subject to inherent limitations such as coding inaccuracies. Further, the dataset used reflects only individuals with fee-for-service Medicare, and the results may not be generalizable to Medicare Advantage or other patient populations. CONCLUSIONS: Assignment to contrast-sparing regimens at a predicted risk threshold close to the underlying incidence of CI-AKI is projected to result in significant clinical and economic benefits.

Climate change disrupts the seasonal coupling of plant and soil microbial nutrient cycling in an alpine ecosystem.

The seasonal coupling of plant and soil microbial nutrient demands is crucial for efficient ecosystem nutrient cycling and plant production, especially in strongly seasonal alpine ecosystems. Yet, how these seasonal nutrient cycling processes are modified by climate change and what the consequences are for nutrient loss and retention in alpine ecosystems remain unclear. Here, we explored how two pervasive climate change factors, reduced snow cover and shrub expansion, interactively modify the seasonal coupling of plant and soil microbial nitrogen (N) cycling in alpine grasslands, which are warming at double the rate of the global average. We found that the combination of reduced snow cover and shrub expansion disrupted the seasonal coupling of plant and soil N-cycling, with pronounced effects in spring (shortly after snow melt) and autumn (at the onset of plant senescence). In combination, both climate change factors decreased plant organic N-uptake by 70% and 82%, soil microbial biomass N by 19% and 38% and increased soil denitrifier abundances by 253% and 136% in spring and autumn, respectively. Shrub expansion also individually modified the seasonality of soil microbial community composition and stoichiometry towards more N-limited conditions and slower nutrient cycling in spring and autumn. In winter, snow removal markedly reduced the fungal:bacterial biomass ratio, soil N pools and shifted bacterial community composition. Taken together, our findings suggest that interactions between climate change factors can disrupt the temporal coupling of plant and soil microbial N-cycling processes in alpine grasslands. This could diminish the capacity of these globally widespread alpine ecosystems to retain N and support plant productivity under future climate change.

Coalescence and sampling distributions for Feller diffusions.

Consider the diffusion process defined by the forward equation ut(t,x)=12{xu(t,x)}xx-α{xu(t,x)}x for t,x≥0 and -∞<α<∞, with an initial condition u(0,x)=δ(x-x0). This equation was introduced and solved by Feller to model the growth of a population of independently reproducing individuals. We explore important coalescent processes related to Feller's solution. For any α and x0>0 we calculate the distribution of the random variable An(s;t), defined as the finite number of ancestors at a time s in the past of a sample of size n taken from the infinite population of a Feller diffusion at a time t since its initiation. In a subcritical diffusion we find the distribution of population and sample coalescent trees from time t back, conditional on non-extinction as t→∞. In a supercritical diffusion we construct a coalescent tree which has a single founder and derive the distribution of coalescent times.

A two-arm, randomised feasibility trial using link workers to improve dental visiting in people with severe mental illness: a protocol paper.

BACKGROUND: People with severe mental illness (e.g. psychosis, bipolar disorder) experience poor oral health compared to the general population as shown by more decayed, missing and filled teeth and a higher prevalence of periodontal disease. Attending dental services allows treatment of oral health problems and support for prevention. However, people with severe mental illness face multiple barriers to attending routine dental appointments and often struggle to access care. Link work interventions use non-clinical support staff to afford vulnerable populations the capacity, opportunity, and motivation to navigate use of services. The authors have co-developed with service users a link work intervention for supporting people with severe mental illness to access routine dental appointments. The Mouth Matters in Mental Health Study aims to explore the feasibility and acceptability of this intervention within the context of a feasibility randomised controlled trial (RCT) measuring outcomes related to the recruitment of participants, completion of assessments, and adherence to the intervention. The trial will closely monitor the safety of the intervention and trial procedures. METHODS: A feasibility RCT with 1:1 allocation to two arms: treatment as usual (control) or treatment as usual plus a link work intervention (treatment). The intervention consists of six sessions with a link worker over 9 months. Participants will be adults with severe mental illness receiving clinical input from secondary care mental health service and who have not attended a planned dental appointment in the past 3 years. Assessments will take place at baseline and after 9 months. The target recruitment total is 84 participants from across three NHS Trusts. A subset of participants and key stakeholders will complete qualitative interviews to explore the acceptability of the intervention and trial procedures. DISCUSSION: The link work intervention aims to improve dental access and reduce oral health inequalities in people with severe mental illness. There is a dearth of research relating to interventions that attempt to improve oral health outcomes in people with mental illness and the collected feasibility data will offer insights into this important area. TRIAL REGISTRATION: The trial was preregistered on ISRCTN (ISRCTN13650779) and ClinicalTrials.gov (NCT05545228).

An estimator for the recombination rate from a continuously observed diffusion of haplotype frequencies.

Recombination is a fundamental evolutionary force, but it is difficult to quantify because the effect of a recombination event on patterns of variation in a sample of genetic data can be hard to discern. Estimators for the recombination rate, which are usually based on the idea of integrating over the unobserved possible evolutionary histories of a sample, can therefore be noisy. Here we consider a related question: how would an estimator behave if the evolutionary history actually was observed? This would offer an upper bound on the performance of estimators used in practice. In this paper we derive an expression for the maximum likelihood estimator for the recombination rate based on a continuously observed, multi-locus, Wright-Fisher diffusion of haplotype frequencies, complementing existing work for an estimator of selection. We show that, contrary to selection, the estimator has unusual properties because the observed information matrix can explode in finite time whereupon the recombination parameter is learned without error. We also show that the recombination estimator is robust to the presence of selection in the sense that incorporating selection into the model leaves the estimator unchanged. We study the properties of the estimator by simulation and show that its distribution can be quite sensitive to the underlying mutation rates.

Cost to Medicare of acute kidney injury in percutaneous coronary intervention.

BACKGROUND: Acute kidney injury (AKI), including contrast-induced AKI (CI-AKI), is an important complication of percutaneous coronary intervention (PCI), resulting in short- and long-term adverse clinical outcomes. While prior research has reported an increased cost burden to hospitals from CI-AKI, the incremental cost to payers remains unknown. Understanding this incremental cost may inform decisions and even policy in the future. The objective of this study was to estimate the short- and long-term cost to Medicare of AKI overall, and specifically CI-AKI, in PCI. METHODS: Patients undergoing inpatient PCI between January 2017 and June 2020 were selected from Medicare 100% fee-for-service data. Baseline clinical characteristics, PCI lesion/procedural characteristics, and AKI/CI-AKI during the PCI admission, were identified from diagnosis and procedure codes. Poisson regression, generalized linear modelling, and longitudinal mixed effects modelling, in full and propensity-matched cohorts, were used to compare PCI admission length of stay (LOS) and cost (Medicare paid amount inflated to 2022 US$), as well as total costs during 1-year following PCI, between AKI and non-AKI patients. RESULTS: The study cohort included 509,039 patients, of whom 104,033 (20.4%) were diagnosed with AKI and 9,691 (1.9%) with CI-AKI. In the full cohort, AKI was associated with +4.12 (95% confidence interval = 4.10, 4.15) days index PCI admission LOS, +$11,313 ($11,093, $11,534) index admission costs, and +$14,800 ($14,359, $15,241) total 1-year costs. CI-AKI was associated with +3.03 (2.97, 3.08) days LOS, +$6,566 ($6,148, $6,984) index admission costs, and +$13,381 ($12,118, $14,644) cumulative 1-year costs (all results are adjusted for baseline characteristics). Results from the propensity-matched analyses were similar. CONCLUSIONS: AKI, and specifically CI-AKI, during PCI is associated with significantly longer PCI admission LOS, PCI admission costs, and long-terms costs.

Staff responses to self-harm by children and young people in mental health inpatient settings: Experiences and views of children and young people, parents and staff.

This study aimed to understand the views of children and young people (CYP), parents and staff on how staff should respond to incidents of self-harm carried out by CYP in mental health inpatient settings. Semi-structured interviews were conducted with CYP (n = 6), parents (n = 5) and mental health professionals (n = 6) with experience of this issue. Data were analysed using reflexive thematic analysis. Two superordinate themes were identified: (1) The threshold for intervening; and (2) Interpersonal attributes of staff. There was general agreement among participants about the interpersonal skills that staff should possess to work safely and effectively with this population. There was disagreement between staff and parent participants about the appropriate threshold for using restrictive interventions to manage incidents of self-harm for this group. Our findings suggest that further work is needed to develop effective approaches for addressing self-harm in this population which are considered acceptable to all key stakeholders. The results of this study could be used to inform future intervention development.

Angiotensin II enhances bacterial clearance via myeloid signaling in a murine sepsis model.

Sepsis, defined as organ dysfunction caused by a dysregulated host-response to infection, is characterized by immunosuppression. The vasopressor norepinephrine is widely used to treat low blood pressure in sepsis but exacerbates immunosuppression. An alternative vasopressor is angiotensin-II, a peptide hormone of the renin-angiotensin system (RAS), which displays complex immunomodulatory properties that remain unexplored in severe infection. In a murine cecal ligation and puncture (CLP) model of sepsis, we found alterations in the surface levels of RAS proteins on innate leukocytes in peritoneum and spleen. Angiotensin-II treatment induced biphasic, angiotensin-II type 1 receptor (AT1R)-dependent modulation of the systemic inflammatory response and decreased bacterial counts in both the blood and peritoneal compartments, which did not occur with norepinephrine treatment. The effect of angiotensin-II was preserved when treatment was delivered remote from the primary site of infection. At an independent laboratory, angiotensin-II treatment was compared in LysM-Cre AT1aR-/- (Myeloid-AT1a-) mice, which selectively do not express AT1R on myeloid-derived leukocytes, and littermate controls (Myeloid-AT1a+). Angiotensin-II treatment significantly reduced post-CLP bacteremia in Myeloid-AT1a+ mice but not in Myeloid-AT1a- mice, indicating that the AT1R-dependent effect of angiotensin-II on bacterial clearance was mediated through myeloid-lineage cells. Ex vivo, angiotensin-II increased post-CLP monocyte phagocytosis and ROS production after lipopolysaccharide stimulation. These data identify a mechanism by which angiotensin-II enhances the myeloid innate immune response during severe systemic infection and highlight a potential role for angiotensin-II to augment immune responses in sepsis.

The interactions and hierarchical effects of long-term agricultural stressors on soil bacterial communities.

Soils are subjected to multiple anthropogenic modifications, but the synergistic impacts of simultaneous environmental stressors on below-ground communities are poorly understood. We used a large-scale (1152 plots), long-term (26 years), multi-factorial grassland experiment to assess the impact of five common agricultural practises (pesticides, herbicide, liming, fertilizers and grazing exclusion) and their interactive effects on the composition and activity of soil microbial communities. We confirmed that pH strongly impacts belowground communities, but further demonstrate that pH strongly mediates the impacts of other management factors. Notably, there was a significant interaction between liming and the effect of pesticide application, with only half of the taxa responding to pesticide being shared in both limed and unlimed treatments. Likewise, nutrient amendments significantly altered bacterial community structure in acidic soils. Not only do these results highlight an hierarchy of effect of commonly used agricultural practices but also the widespread interactions between treatments: many taxa were significantly affected by interactions between treatments, even in the absence of significant main effects. Furthermore, the results demonstrated that chemical amendments may not percolate deeply into physically unperturbed soils with effects concentrated between 0 and 30 cm, despite 20+ years of treatment. The research shows that future changes to agricultural practices will need to consider interactions among multiple factors.

Temporal trends of device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients with underlying kidney disease.

BACKGROUND: Kidney disease is a risk factor for device infection in transvenous implantable cardioverter-defibrillator (TV-ICD) implants, with mechanisms that include immunodeficiency and a portal of entry for bacteria that can seed indwelling devices. OBJECTIVE: The purpose of this study was to examine the impact of both kidney disease and dialysis-dependence on the incidence of device-related infection after de novo TV-ICD implantation and how the incidence changes over time in. METHODS: Medicare 100% administrative and claims data were used to identify patients who underwent de novo TV-ICD implantation between July 1, 2016, and December 31, 2018. Baseline characteristics included underlying kidney disease (none, nondialysis, dialysis) plus device infection during follow-up. Patients were followed for TV-ICD infection up to 78 weeks after implantation. Piecewise Poisson regression was used to predict the incidence of and hazard ratios for infection over time. RESULTS: Overall, 809 of 42,200 patients (1.9%) had at least 1 device infection during mean follow-up of 66 weeks: 484 of 31,217 (1.6%) none; 202 of 9151 (2.2%) nondialysis; and 123 of 1832 (6.7%) dialysis (P <.001 via log-rank test). The incidence of infection increased during the first 8-12 weeks and declined thereafter. Hazard ratios increased over time (dialysis week 12 = 4.9/1000 patient-years; week 52 = 9.8; nondialysis week 12 = 1.4; week 52 = 2.5; all P <.05), as did the difference in cumulative incidence compared with none (dialysis week 12 = Δ11.8 and week 78 = Δ53.5; nondialysis week 12 = Δ1.4 and week 78 = Δ7.0). CONCLUSION: The incidence of infection after de novo TV-ICD implantation is higher when patients have kidney disease and is substantially higher when patients are dialysis-dependent.

Cost-effectiveness of a paclitaxel-eluting stent (Eluvia) compared to Zilver PTX for endovascular femoropopliteal intervention.

OBJECTIVES: Antiproliferative therapies based on paclitaxel have been developed to extend the durability of endovascular interventions for lower-extremity atherosclerotic peripheral artery disease, resulting in improved primary vessel patency and fewer target lesion revascularizations. This study evaluated the cost-effectiveness of the sustained-release, paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) for endovascular intervention in the superficial femoral or proximal popliteal artery. DESIGN: A microsimulation model was constructed from a United States Medicare perspective with a 24-month time horizon. Patients entering the model were assigned to initial endovascular intervention with either Eluvia or Zilver PTX. Each month patients were exposed to the risks of primary vessel patency loss, target lesion revascularization, amputation, and death. Clinical input parameters were taken from a randomized trial (IMPERIAL) comparing the two interventions at 24-months follow-up. Cost parameters were obtained from analyses of Medicare administrative and claims data. Cost-effectiveness analysis entailed sampling a complete set of clinical and cost parameters from their respective distributions, and then running cohorts of 10,000 patients through each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case microsimulation, at 24 months, the modeled target lesion revascularization was 11.6% for Eluvia and 19.0% for Zilver PTX, and the mean total direct costs were $20,010 and $21,356, respectively (Eluvia average savings=$1,346). In probabilistic sensitivity analyses, Eluvia was cost-effective in 87.8% of all simulations at a willingness-to-pay threshold of $10,000 per target lesion revascularization prevented. Eluvia was more effective and less costly (dominant) than Zilver PTX in 73.6% of simulations. CONCLUSIONS: In this comparison of a paclitaxel-eluting to a paclitaxel-coated stent for endovascular femoropopliteal intervention, Eluvia was more effective and less costly (dominant) than Zilver PTX from a US Medicare perspective. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Paclitaxel is a drug used in the treatment of peripheral artery disease (PAD) to help maintain primary vessel patency and reduce the need for revascularization procedures. This study evaluated the cost-effectiveness of the paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) in Medicare patients with PAD. Cost-effectiveness is defined as the degree to which a particular treatment option is effective relative to its costs. Therefore, this study compared both the effectiveness, in terms of target lesion revascularization rates, and the costs of Eluvia versus Zilver PTX over 24 months.A microsimulation model was developed from a United States Medicare perspective with a 24-month time horizon. Simulated patients entered the model and were assigned to receive either Eluvia or Zilver PTX. Monthly, patients were exposed to the risks of primary vessel patency loss, target lesion revascularization (TLR), amputation, and death. These risks were taken from a randomized controlled trial that compared Eluvia and Zilver PTX over 24 months. Patients also accrued costs over time. The costs used in the model were obtained from Medicare administrative and claims data analyses.In health economics, a treatment is considered to be the dominant treatment option if it is both more effective and less costly than the alternative treatment. In this case, Eluvia was found to be dominant over Zilver PTX because it was associated with lower TLR rates and lower costs. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Type 1 Angiotensin Receptors on CD11c-Expressing Cells Protect Against Hypertension by Regulating Dendritic Cell-Mediated T Cell Activation.

BACKGROUND: Type 1 angiotensin (AT1) receptors are expressed on immune cells, and we previously found that bone marrow-derived AT1 receptors protect against Ang (angiotensin) II-induced hypertension. CD11c is expressed on myeloid cells derived from the bone marrow, including dendritic cells (DCs) that activate T lymphocytes. Here, we examined the role of AT1 receptors on CD11c+ cells in hypertension pathogenesis. METHODS: Mice lacking the dominant murine AT1 receptor isoform, AT1a, on CD11c+ cells (dendritic cell [DC] AT1aR knockout [KO]) and wild-type (WT) littermates were subjected to Ang II-induced hypertension. Blood pressures were measured by radiotelemetry. RESULTS: DC AT1aR KO mice had exaggerated hypertensive responses to chronic Ang II infusion with enhanced renal accumulation of effector memory T cells and CD40+ DCs. CCL5 (C-C motif chemokine ligand 5) recruits T cells into injured tissues, and CCR7 (C-C motif chemokine receptor 7) facilitates DC and T cell interactions in the kidney lymph node to allow T cell activation. DCs from the hypertensive DC AT1aR KO kidneys expressed higher levels of CCL5 and CCR7. mRNA expressions for CCR7 and tumor necrosis factor-α were increased in CD4+ T cells from the renal lymph nodes of DC AT1aR KO mice. During the second week of Ang II infusion when blood pressures between groups diverged, DC AT1aR KO mice excreted less sodium than WTs. Expressions for epithelial sodium channel subunits were increased in DC AT1aR KO kidneys. CONCLUSIONS: Following activation of the renin angiotensin system, AT1aR stimulation on DCs suppresses renal DC maturation and T cell activation with consequent protection from sodium retention and blood pressure elevation.

Device-related infection associated with increased mortality risk in de novo transvenous implantable cardioverter-defibrillator medicare patients.

INTRODUCTION: Transvenous implantable cardioverter-defibrillators (TV-ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV-ICD infection in a large Medicare population with de novo TV-ICD implants. METHODS: A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent de novo TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias. RESULTS: Among 26,742 Medicare patients with de novo TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 (95% CI: 2.08-2.85) times in the mortality hazard ratio. CONCLUSION: The rate of TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections.

Non-restrictive interventions to reduce self-harm amongst children in mental health inpatient settings: Systematic review and narrative synthesis.

Rates of self-harm amongst children appear to be increasing. This presents challenges for practitioners responsible for maintaining the safety of children admitted to mental health inpatient settings. Policy guidelines recommend that practitioners should aim to avoid the use of restrictive practices for children. It is currently unclear, however, what evidence-based alternatives to restrictive practices are available. We aimed to identify what non-restrictive interventions have been proposed to reduce self-harm amongst children in mental health inpatient settings and to evaluate the evidence supporting their use in clinical practice. A systematic search of five databases (CINAHL, Embase, Ovid MEDLINE, APA Psycinfo, and Cochrane) was conducted to identify articles reporting on non-restrictive interventions aimed at reducing self-harm amongst children in mental health inpatient settings. Articles were quality assessed and relevant data were extracted and synthesized using narrative synthesis. Searches identified relatively few relevant articles (n = 7) and these were generally of low methodological quality. The underlying theoretical assumptions and putative mechanisms of change for the interventions described were often unclear. Despite concerns about the rates of self-harm amongst children in mental health inpatient settings, there is a lack of high-quality research to inform clinical practice. There is an urgent need to develop effective non-restrictive interventions aimed at reducing self-harm for children using inpatient mental health services. Intervention development should be theoretically informed and be conducted in collaboration with people who have lived experience of this issue.

Shrub expansion modulates belowground impacts of changing snow conditions in alpine grasslands.

Climate change is disproportionately impacting mountain ecosystems, leading to large reductions in winter snow cover, earlier spring snowmelt and widespread shrub expansion into alpine grasslands. Yet, the combined effects of shrub expansion and changing snow conditions on abiotic and biotic soil properties remains poorly understood. We used complementary field experiments to show that reduced snow cover and earlier snowmelt have effects on soil microbial communities and functioning that persist into summer. However, ericaceous shrub expansion modulates a number of these impacts and has stronger belowground effects than changing snow conditions. Ericaceous shrub expansion did not alter snow depth or snowmelt timing but did increase the abundance of ericoid mycorrhizal fungi and oligotrophic bacteria, which was linked to decreased soil respiration and nitrogen availability. Our findings suggest that changing winter snow conditions have cross-seasonal impacts on soil properties, but shifts in vegetation can modulate belowground effects of future alpine climate change.

Soluble ACE2 Is Filtered into the Urine.

Background: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, abundance of ACE2 is highest in the kidney, and it is also expressed in several extrarenal tissues. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2-knockout mice. Methods: To examine the effect of ACE2 expressed in the kidney, relative to extrarenal expression, on the development of hypertension, we used a kidney crosstransplantation strategy with ACE2-KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney, such that four experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we used nanoscale mass spectrometry-based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. Results: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice that lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII-mediated hypertension suggests that sACE2 originating from extrarenal tissues can reach the kidney and be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nanoscale proteomics to detect peptides derived from ACE2 in the Bowman's space. Conclusions: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular filtration barrier.

Shifts in Soil Structure, Biological, and Functional Diversity Under Long-Term Carbon Deprivation.

Soil organic matter is composed of a variety of carbon (C) forms. However, not all forms are equally accessible to soil microorganisms. Deprivation of C inputs will cause changes in the physical and microbial community structures of soils; yet the trajectories of such changes are not clear. We assessed microbial communities using phospholipid fatty acid profiling, metabarcoding, CO2 emissions, and functional gene microarrays in a decade-long C deprivation field experiment. We also assessed changes in a range of soil physicochemical properties, including using X-ray Computed Tomography imaging to assess differences in soil structure. Two sets of soils were deprived of C inputs by removing plant inputs for 10 years and 1 year, respectively. We found a reduction in diversity measures, after 10 years of C deprivation, which was unexpected based on previous research. Fungi appeared to be most impacted, likely due to competition for scarce resources after exhausting the available plant material. This suggestion was supported by evidence of bioindicator taxa in non-vegetated soils that may directly compete with or consume fungi. There was also a reduction in copies of most functional genes after 10 years of C deprivation, though gene copies increased for phytase and some genes involved in decomposing recalcitrant C and methanogenesis. Additionally, soils under C deprivation displayed expected reductions in pH, organic C, nitrogen, and biomass as well as reduced mean pore size, especially in larger pores. However, pore connectivity increased after 10 years of C deprivation contrary to expectations. Our results highlight concurrent collapse of soil structure and biodiversity following long-term C deprivation. Overall, this study shows the negative trajectory of continuous C deprivation and loss of organic matter on a wide range of soil quality indicators and microorganisms.

Beyond Taxonomic Identification: Integration of Ecological Responses to a Soil Bacterial 16S rRNA Gene Database.

High-throughput sequencing 16S rRNA gene surveys have enabled new insights into the diversity of soil bacteria, and furthered understanding of the ecological drivers of abundances across landscapes. However, current analytical approaches are of limited use in formalizing syntheses of the ecological attributes of taxa discovered, because derived taxonomic units are typically unique to individual studies and sequence identification databases only characterize taxonomy. To address this, we used sequences obtained from a large nationwide soil survey (GB Countryside Survey, henceforth CS) to create a comprehensive soil specific 16S reference database, with coupled ecological information derived from survey metadata. Specifically, we modeled taxon responses to soil pH at the OTU level using hierarchical logistic regression (HOF) models, to provide information on both the shape of landscape scale pH-abundance responses, and pH optima (pH at which OTU abundance is maximal). We identify that most of the soil OTUs examined exhibited a non-flat relationship with soil pH. Further, the pH optima could not be generalized by broad taxonomy, highlighting the need for tools and databases synthesizing ecological traits at finer taxonomic resolution. We further demonstrate the utility of the database by testing against geographically dispersed query 16S datasets; evaluating efficacy by quantifying matches, and accuracy in predicting pH responses of query sequences from a separate large soil survey. We found that the CS database provided good coverage of dominant taxa; and that the taxa indicating soil pH in a query dataset corresponded with the pH classifications of top matches in the CS database. Furthermore we were able to predict query dataset community structure, using predicted abundances of dominant taxa based on query soil pH data and the HOF models of matched CS database taxa. The database with associated HOF model outputs is released as an online portal for querying single sequences of interest (https://shiny-apps.ceh.ac.uk/ID-TaxER/), and flat files are made available for use in bioinformatic pipelines. The further development of advanced informatics infrastructures incorporating modeled ecological attributes along with new functional genomic information will likely facilitate large scale exploration and prediction of soil microbial functional biodiversity under current and future environmental change scenarios.

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients.

BACKGROUND: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection. OBJECTIVE: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population. METHODS: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted. RESULTS: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus. CONCLUSION: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection.