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Abstract Soil microbiomes are heterogeneous, complex microbial communities. Metagenomic analysis is generating vast amounts of data, creating immense challenges in sequence assembly and analysis. Although advances in technology have resulted in the ability to easily collect large amounts of sequence data, soil samples containing thousands of unique taxa are often poorly characterized. These challenges reduce the usefulness of genome-resolved metagenomic (GRM) analysis seen in other fields of microbiology, such as the creation of high quality metagenomic assembled genomes and the adoption of genome scale modeling approaches. The absence of these resources restricts the scale of future research, limiting hypothesis generation and the predictive modeling of microbial communities. Creating publicly available databases of soil MAGs, similar to databases produced for other microbiomes, has the potential to transform scientific insights about soil microbiomes without requiring the computational resources and domain expertise for assembly and binning.

Abstract Background Although elderly population is generally frail, it is important to closely monitor their health deterioration to improve the care and support in residential aged care homes (RACs). Currently, the best identification approach is through time-consuming regular geriatric assessments. This study aimed to develop and validate a retrospective electronic frailty index (reFI) to track the health status of people staying at RACs using the daily routine operational data records. Methods We have access to patient records from the Royal Freemasons Benevolent Institution RACs (Australia) over the age of 65, spanning 2010 to 2021. The reFI was developed using the cumulative deficit frailty model whose value was calculated as the ratio of number of present frailty deficits to the total possible frailty indicators (32). Frailty categories were defined using population quartiles. 1, 3 and 5-year mortality were used for validation. Survival analysis was performed using Kaplan-Meier estimate. Hazard ratios (HRs) were estimated using Cox regression analyses and the association was assessed using receiver operating characteristic (ROC) curves. Results Two thousand five hundred eighty-eight residents were assessed, with an average length of stay of 1.2 ± 2.2 years. The RAC cohort was generally frail with an average reFI of 0.21 ± 0.11. According to the Kaplan-Meier estimate, survival varied significantly across different frailty categories (p

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide (LPS), which is known to polarize macrophages towards a classically activated phenotype and 3) Interleukin-4 (IL-4), which is known to promote polarization of macrophages towards an alternatively activated phenotype. NCEs provoke changes in differential gene expression (DEGs) that had considerable overlap with LPS-induced changes, suggesting that NCEs promote macrophage polarization towards a classically activated phenotype. Treating NCEs with proteinase-K abolished the effects of NCEs on macrophage activation, whereas NCE treatment with DNase and RNase did not affect macrophage activation. Stimulation of macrophage cultures with NCEs and LPS resulted in a significant increase in macrophage phagocytosis and interleukin-1β secretion, whereas treatment with IL-4 had no significant effect on phagocytosis and interleukin-1β. Taken together, our findings suggest that proteins released from necrotic cardiac myocytes are sufficient to skew the polarization of macrophages towards a classically activated phenotype.

Switchgrass (Panicum virgatum L.) remains the preeminent American perennial (C4) bioenergy crop for cellulosic ethanol, that could help displace over a quarter of the US current petroleum consumption. Intriguingly, there is often little response to nitrogen fertilizer once stands are established. The rhizosphere microbiome plays a critical role in nitrogen cycling and overall plant nutrient uptake. We used high-throughput metagenomic sequencing to characterize the switchgrass rhizosphere microbial community before and after a nitrogen fertilization event for established stands on marginal land. We examined community structure and bulk metabolic potential, and resolved 29 individual bacteria genomes via metagenomic de novo assembly. Community structure and diversity were not significantly different before and after fertilization; however, the bulk metabolic potential of carbohydrate-active enzymes was depleted after fertilization. We resolved 29 metagenomic assembled genomes, including some from the ‘most wanted’ soil taxa such as Verrucomicrobia, Candidate phyla UBA10199, Acidobacteria (rare subgroup 23), Dormibacterota, and the very rare Candidatus Eisenbacteria. The Dormibacterota (formally candidate division AD3) we identified have the potential for autotrophic CO utilization, which may impact carbon partitioning and storage. Our study also suggests that the rhizosphere microbiome may be involved in providing associative nitrogen fixation (ANF) via the novel diazotroph Janthinobacterium to switchgrass.

Objective: We aimed to understand the extent of hospitalist involvement in system improvement efforts across the province of British Columbia in Canada and provide insights into determinants of such participation. Materials and Methods: We designed a web-based survey and asked about individual, programmatic, and institutional characteristics that may facilitate or impair hospitalist involvement in quality improvement (QI) activities. The survey was sent to all individuals who participated in “hospitalist care” from January 2014 to February 2015, in the province of British Columbia, Canada. We conducted both quantitative and qualitative analysis of responses. Results: We received 57 complete responses to the survey of 322 invited individuals (17.7% response rate). Of these, 15 individuals (26.3%) indicated that they had participated in QI initiatives. Respondents highlighted high clinical workload and lack of time, lack of QI skills and training, lack of access to performance data, poor support from hospital/health authority administration, and lack of financial compensation as main barriers to QI involvement. These themes were also supported in logistic regression, where QI training and the number of weeks worked as a hospitalist showed significant predictive properties for involvement in QI initiatives. Conclusion: Our study attempts to understand the various individual or organizational attributes that could facilitate involvement by hospital-based generalist physicians in QI activities. Our findings show lack of formal QI training is an important barrier for hospitalist involvement in QI, and highlight the need for formal training, dedicated time, support from physician leadership, and financial incentive as important facilitators for participation in systemic improvement efforts.

Patients infected with HIV benefit from early diagnosis, allowing initiation of highly effective treatment to reduce the risk of complications and onward infection.Current NICE guidelines recommend routine screening in all individuals accessing healthcare where the population prevalence exceeds 2/10001,2. The prevalence of diagnosed HIV is 1.23/1000 in Oxfordshire. Despite this, over 30% of patients are diagnosed late with a low CD4 count.In this quality improvement project (QIP), we set out to normalise HIV testing in the ambulatory assessment unit by adopting an opt-out testing approach. Our aim was to screen 90% of patients per month by December 2020. Methods: The QIP was first established in November 2018. The second was embarked in 2019, but impeded by the recent pandemic. Our third cycle was from September 2020 toDecember 2020. The percentage of AAU patients undergoing HIV screening was recorded each month by trust data analysts.Key interventions implemented include: * Distribution of poster prompts. * Creation of a medical referral ‘autotext’ template. * Education of nursing/healthcare assistant staff. * Introduction of a multidisciplinary group of “HIV champions”

PurposeImpaired glucose metabolism is present in most patients with pancreatic ductal adenocarcinoma (PDAC). Whereas previous studies have focused on pre-treatment glycemic indices and prognosis in those with concomitant diabetes, the effects of glycemic control during chemotherapy treatment on prognosis, in patients with and without diabetes, have not been well characterized. We examined the relationship between early glycemic control and overall survival (OS) in a cohort of patients with advanced PDAC treated in a community setting.Patients and MethodsSeventy-three patients with advanced PDAC (38% with diabetes) receiving chemotherapy while participating in a biobanking clinical trial were included. Clinical characteristics and laboratory results during 1 year were obtained from the electronic medical record. Kaplan-Meier estimate, log-rank test and hazard ratios were computed to assess the effect of glycemic control on OS. The Cox proportional hazards regression model was applied to ascertain the significance of glycemic control with other survival variables.ResultsOne thousand four hundred eighteen random blood glucose (RBG) values were analyzed. In accord with previous findings, a 50% decline in the serum tumor marker CA 19-9 at any time was predictive of survival (P=0.0002). In univariate analysis, an elevated pre-treatment average RBG, 3-month average RBG (RBG-3) and the FOLFIRINOX regimen were associated with longer survival. Based on ROC analysis (AUC=0.82), an RBG-3 of 120 mg/dl was determined to be the optimal cutoff to predict 12-month survival. In multivariate analysis that included age, stage, BMI, performance status, presence of diabetes, and chemotherapy regimen, only RBG-3 maintained significance: an RBG-3 ≤120 mg/dl predicted for improved OS compared to >120 mg/dl (19 vs. 9 months; HR=0.37, P=0.002). In contrast, an early decline in CA 19-9 could not predict OS.ConclusionLower glucose levels during the first 3 months of treatment for advanced PDAC predict for improved OS in patients both with and without diabetes. These results suggest that RBG-3 may be a novel prognostic biomarker worthy of confirmation in a larger patient cohort and that studies exploring a possible cause and effect of this novel survival-linked relationship are warranted.

Introduction Currently, we are unable to accurately predict mortality or neurological morbidity following resuscitation after paediatric out of hospital (OHCA) or in-hospital (IHCA) cardiac arrest. A clinical prediction model may improve communication with parents and families and risk stratification of patients for appropriate postcardiac arrest care. This study aims to the derive and validate a clinical prediction model to predict, within 1 hour of admission to the paediatric intensive care unit (PICU), neurodevelopmental outcome at 3 months after paediatric cardiac arrest.Methods and analysis A prospective study of children (age: >24 hours and

Set in the Capitalocene, this conceptual paper examines 'sustainability' in ecological education through a posthuman lens. I demonstrate how the Deleuzoguattarian concept of the refrain helps reconfigure the function of 'sustainability' as an affective force of unstable-stabilizing when facing increasingly violent climate crisis events. Currently, ecological education and 'sustainability' are presented as solutions to these effects. How 'sustainable' something is, is increasingly used as a standard to expound its virtues - especially in the marketing of products, consumables, and energy. However, aligning with eco-feminist new material critiques, I propose that sustainability has sedimented into a regime of inertia, functioning to perpetuate practices known to be harmful to the environment as an order-word of stoppage. This paper offers new perspectives to problems presented in the language of environmental education, in order to suggest radical reimaginings for practice in the development of pedagogy capable of harnessing the chaos of climate crisis.

ObjectiveBrain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD.MethodTwenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures.ResultsPost-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group.ConclusionThis study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

We analyze a radius bone fragment of a raven (Corvus corax) from Zaskalnaya VI rock shelter, Crimea. The object bears seven notches and comes from an archaeological level attributed to a Micoquian industry dated to between 38 and 43 cal kyr BP. Our study aims to examine the degree of regularity and intentionality of this set of notches through their technological and morphometric analysis, complemented by comparative experimental work. Microscopic analysis of the notches indicate that they were produced by the to-and-fro movement of a lithic cutting edge and that two notches were added to fill in the gap left between previously cut notches, probably to increase the visual consistency of the pattern. Multivariate analysis of morphometric data recorded on the archaeological notches and sets of notches cut by nine modern experimenters on radii of domestic turkeys shows that the variations recorded on the Zaskalnaya set are comparable to experimental sets made with the aim of producing similar, parallel, equidistant notches. Identification of the Weber Fraction, the constant that accounts for error in human perception, for equidistant notches cut on bone rods and its application to the Zaskalnaya set of notches and thirty-six sets of notches incised on seventeen Upper Palaeolithic bone objects from seven sites indicate that the Zaskalnaya set falls within the range of variation of regularly spaced experimental and Upper Palaeolithic sets of notches. This suggests that even if the production of the notches may have had a utilitarian reason the notches were made with the goal of producing a visually consistent pattern. This object represents the first instance of a bird bone from a Neanderthal site bearing modifications that cannot be explained as the result of butchery activities and for which a symbolic argument can be built on direct rather than circumstantial evidence.

Background: Early elevation in blood pressure are characterised by a hyperkinetic circulation, with an elevated cardiac index (CI) being the dominant feature. Neuronal NOS is a key regulator of vascular tone during mental stress and is attenuated in patients with established hypertension. However, the role of nNOS has not yet been examined in young adults with a hyperactive response to stress. Methods: 20 subjects (M:11, 28±6 years) were dichotomised into high and low CI. Forearm blood flow (FBF) was measured using strain gauge plethysmography at rest and during a word interference test (Stroop); before and after the infusion of the nNOS-specific inhibitor, S-methyl-l-citrulline (SMTC). Results: Cardiac index was 2.88±0.7 versus 4.32±0.9 L/min/m2 in the low and high groups, respectively. Mental stress induced a marked increase in FBF in subjects with high CI versus low CI, which was signficantly blunted after infusion of SMTC (P

The hyper-arid western Namib Sand Sea (mean annual rainfall 0-17 mm) is a detritus-based ecosystem in which primary production is driven by large, but infrequent rainfall events. A diverse Namib detritivore community is sustained by minimal moisture inputs from rain and fog. The decomposition of plant material in the Namib Sand Sea (NSS) has long been assumed to be the province of these detritivores, with beetles and termites alone accounting for the majority of litter losses. We have found that a mesophilic Ascomycete community, which responds within minutes to moisture availability, is present on litter of the perennial Namib dune grass Stipagrostis sabulicola. Important fungal traits that allow survival and decomposition in this hyper-arid environment with intense desiccation, temperature and UV radiation stress are darkly-pigmented hyphae, a thermal range that includes the relatively low temperature experienced during fog and dew, and an ability to survive daily thermal and desiccation stress at temperatures as high as 50°C for five hours. While rainfall is very limited in this area, fog and high humidity provide regular periods (≥ 1 hour) of sufficient moisture that can wet substrates and hence allow fungal growth on average every 3 days. Furthermore, these fungi reduce the C/N ratio of the litter by a factor of two and thus detritivores, like the termite Psammotermes allocerus, favor fungal-infected litter parts. Our studies show that despite the hyper-aridity of the NSS, fungi are a key component of energy flow and biogeochemical cycling that should be accounted for in models addressing how the NSS ecosystem will respond to projected climate changes which may alter precipitation, dew and fog regimes.

Background: Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) were an initiative of the National Institute for Health Research in response to a new research and development strategy in the NHS: ‘Best Research for Best Health’. They were designed to address the ‘second gap in translation’ identified by the Cooksey review; namely, the need to improve health care in the UK by translating clinical research into practice more effectively. Nine CLAHRCs, each encompassing a university in partnership with local NHS bodies, were funded over the period 2008–13. Aims: The aim of this report is to provide an independent and theory-based evaluation of CLAHRCs as a new form of networked innovation in the health sector. This evaluation is based on an intensive research study involving three CLAHRCs in the UK and three international organisations (one in the USA and two in Canada). This study was carried out over two overlapping time phases so as to capture changes in the CLAHRCs over time. Networked innovation in the health sector is conceptualised as involving the translation of knowledge via informal social networks. Methods: A mix of research methods was used to help ensure the validity and generalisability of the study. These methods addressed the development of each CLAHRC over time, over multiple levels of analysis, and with particular reference to the translation of knowledge across the groups involved, and the quality of the informal underpinning network ties that supported such translation. Research methods, therefore, included a qualitative enquiry based on case studies and case analysis, cognitive mapping methods, and social network analysis. Findings: Through our study, we found that each one of our samples of CLAHRCs appropriated the CLAHRC idea in a particular way, depending on their different interpretations or ‘visions’ of the CLAHRC’s role in knowledge translation (KT), and different operating models of how such visions could be achieved. These helped to shape the development of social networks (centralised vs. decentralised) and each CLAHRC’s approach to KT activity (‘bridging’ vs. ‘blurring’ the boundaries between professional groups). Through a comparative analysis, we develop an analytical model of the resultant capabilities which each case, including our international sites, developed for undertaking innovation, encompassing a combination of both ‘integrative capability’ (the ability to move back and forth between scientific evidence and practical application) and ‘relational capability’ (the ability of groups and organisations to work together). This extends previous models of KT by highlighting the effects of leadership and management, and the emergence of social network structures. We further highlight the implications of this analysis for policy and practice by discussing how network structures and boundary-spanning roles and activities can be tailored to different KT objectives. Conclusions: Different interpretations and enactments of the CLAHRC mission ultimately led to differing capabilities for KT among our studied initiatives. Further research could usefully explore how these different capabilities are produced, and how they may be more or less appropriate for particular national health-care settings, with a view to improving the design blueprint for future KT initiatives. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

BackgroundSerum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.Methods and findingsWe expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 microM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 microM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82).ConclusionsThis study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.

Background: Visual-spatial and visual-motor perceptual difficulties contribute to school-aged learning problems. Hence, a need exists to address children’s visual-spatial and visual-motor perceptual difficulties as early as possible in the child’s school career. Thus, this study reports on the evaluation of the Anker Bilateral Spatial System’s (ABSS) effectiveness in remediating primary school children’s perceptual difficulties. Method: Thirty-one children (17 boys and 14 girls) aged 6 to 12 years who had been identified by their classroom teacher as having observable visual-spatial and visual-motor perceptual difficulties participated in a 10-week pre/posttest intervention study. The study’s pre/posttest assessments included the Developmental Test of Visual-Motor Integration (VMI), the Spatial Awareness Skills Program Test (SASP), and two subscales of the School Function Assessment (SFA). Results: Paired t-test statistics were calculated on the pre/post intervention scores. Paired t-test statistics calculated (p = .05) that significant change had occurred in the writing speed (t = -3.978, p < .001). Conclusion: Given that the study’s Year 1 students made progress in more areas of remediation than did any other year level, it is evident that the ABSS is particularly effective with this year group.