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Abstract Background An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. Methods The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3–5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index – Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. Discussion This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial’s findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. Trial registration ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).

Background: Hypertension is considered the most important risk factor for cardiovascular diseases, but its control is poor worldwide. We aimed to assess the availability and affordability of blood pressure-lowering medicines, and the association with use of these medicines and blood pressure control in countries at varying levels of economic development. Methods: We analysed the availability, costs, and affordability of blood pressure-lowering medicines with data recorded from 626 communities in 20 countries participating in the Prospective Urban Rural Epidemiological (PURE) study. Medicines were considered available if they were present in the local pharmacy when surveyed, and affordable if their combined cost was less than 20% of the households' capacity to pay. We related information about availability and affordability to use of these medicines and blood pressure control with multilevel mixed-effects logistic regression models, and compared results for high-income, upper-middle-income, lower-middle-income, and low-income countries. Data for India are presented separately because it has a large generic pharmaceutical industry and a higher availability of medicines than other countries at the same economic level. Findings: The availability of two or more classes of blood pressure-lowering drugs was lower in low-income and middle-income countries (except for India) than in high-income countries. The proportion of communities with four drug classes available was 94% in high-income countries (108 of 115 communities), 76% in India (68 of 90), 71% in upper-middle-income countries (90 of 126), 47% in lower-middle-income countries (107 of 227), and 13% in low-income countries (nine of 68). The proportion of households unable to afford two blood pressure-lowering medicines was 31% in low-income countries (1069 of 3479 households), 9% in middle-income countries (5602 of 65 471), and less than 1% in high-income countries (44 of 10 880). Participants with known hypertension in communities that had all four drug classes available were more likely to use at least one blood pressure-lowering medicine (adjusted odds ratio [OR] 2·23, 95% CI 1·59–3·12); p

Abstract Background In recognition of the burden of Perinatal Mental Health problems, NHS England invested £365 million to transform women’s access to mental health care, including investment in Community Perinatal Mental Health Services. This study examined how elements of provider care affected women’s engagement with these services. Methods Semi-structured interviews were conducted with 139 women and explored their experiences of care from 10 different Community Perinatal Mental Health Teams; including which service components participants believed made a difference to their initial and continued engagement. Realist analysis was used to create context-mechanism-outcome configurations (CMOCs) across interviews, since not all parts of the configurations were always articulated within singular interviews. Results Four key pillars for engagement were identified: perinatal competence, relationship building, accurate reassurance, and reliability. The way perinatal competencies were relayed to women mattered; compassion, understanding and consistency were critical interactional styles. The extent to which these factors affected women’s engagement varied by their context and personal characteristics. Conclusions As mental health problems increase, disproportionately affecting vulnerable populations, it is critical to continue to ensure support is not only available, but appropriately meets the needs of those individuals. Our findings suggest that key staff behaviours applied at the right time can support women’s engagement and potentially contribute to better treatment outcomes.

Abstract Socio‐ecological resilience is the capacity of a system to adapt to changing ecological and social disturbances. Its assessment is extremely important to integrate long‐term management of ecological and social features of natural ecosystems. This is especially true for Sacred Natural Sites, such as sacred forests and groves, where it can reveal the influence of social processes in ecosystem recovery or degradation. Using tree ages determined through dendrochronology and tree population size‐class distributions collected in five sacred forests in Epirus (NW Greece), we explore spatial and temporal dynamics of resilience in a socio‐ecological system, identifying which cultural and social elements characterize resilience in space and time. Our main results show that over past centuries sacred forests in Epirus underwent periods of varying tree establishment rate, depending on the intensity of human activities and historical disturbance events. We also identified strong evidence of the role of the social component (i.e. the church and associated cultural praxis) in determining the spatial extent of the forests' current recovery phase, and thus the overall resilience of the system. Policy implications. Appreciation of the ways sacred forests' ecological resilience is linked to changing socio‐cultural praxis over both temporal and spatial scales is crucial for guiding conservation and restoration strategies. We argue that greater attention should be paid to the role of the social component of socio‐ecological systems and specifically for sacred natural sites that provide both a nucleus of established forest habitat and the conditions necessary for forest recovery and restoration. Read the free Plain Language Summary for this article on the Journal blog.

Chagas disease is an inflammatory parasitic infection caused by Trypanosoma cruzi (T. cruzi). Early diagnosis is crucial in guiding treatment and slowing disease progression; however, current diagnostic methods have insufficient detection limits and often require skilled technicians. Molecular tests, especially isothermal nucleic acid assays, are advantageous due to their excellent sensitivity, specificity, speed, and simplicity. Here, we optimized a colorimetric loop-mediated isothermal amplification (LAMP) assay for T. cruzi. We can detect as few as 2 genomic copies/reaction using three different T. cruzi strains. We examined selectivity using other parasitic protozoans and successfully detected T. cruzi DNA extracted from parasites in human whole blood down to 1.2 parasite equivalents/reaction. We also performed a blinded study using canine blood samples and established a 100% sensitivity, specificity, and accuracy for the colorimetric LAMP assay. Finally, we used a heated 3D printer bed and an insulated thermos cup to demonstrate that the LAMP incubation step could be performed with accessible, low-cost materials. Altogether, we have developed a high-performing assay for T. cruzi with a simple colorimetric output that would be ideal for rapid, low-cost screening at the point of use.

Changing climates are causing agricultural water shortages at unprecedented scales and magnitudes, especially in regions historically reliant on irrigation. Identifying and understanding systems of farming that allow continuity in agricultural operations in times of water scarcity are increasingly urgent needs. Vegetable dry farming relies on winter rains stored in soils to reduce irrigation to 0–2 events per season and has become prevalent on California’s Central Coast in recent decades. Until now, this system has been unexplored in scientific literature beyond extension publications, despite its promise as a model for low-water agriculture in arid regions. Dry farm management presents a unique challenge given that low water content restricts nutrient access in surface soils, which farmers typically target for fertility management. Managing soil nutrients at depth, as well as microorganisms that help plants access nutrients and alleviate water stress (e.g. arbuscular mycorrhizal fungi, or AMF) could be crucial to dry farm success. We engaged in a collaborative research design process with farmers managing seven commercial dry farm tomato fields to identify and answer three key management questions: 1. What are the depths at which nutrients influence harvest outcomes given low water content in surface soils?, 2. Are commercially available AMF inoculants effective at improving harvest outcomes?, and 3. How does the broader fungal community change in dry farm soils, and are those changes associated with harvest outcomes? Only soil nutrients below 60 cm depth were correlated with tomato yield and fruit quality. We identified a fungal class, Sordariomycetes, as a ‘signature’ fungal group in dry farm soils that distinguished them from irrigated management and correlated with positive fruit quality, while commercial AMF inoculation showed little benefit. These findings can inform management practices that optimize fruit yield and quality, and can guide farmers and policymakers alike in efforts to minimize agricultural water use.

Objective To estimate the surgical burden of malignant disease in the Eastern Region of Ghana.Design Descriptive cross-sectional study.Setting Regional hospital in the eastern region of Ghana.Participants Patients treated by the surgery department at Eastern Regional Hospital in Koforidua, Ghana.Interventions None.Primary and secondary outcome measures Primary outcome was incidence of malignancy and secondary outcome descriptive differences between patients who had a benign indication for surgery compared with those with a malignant indication for surgery.Results A total of 1943 inpatient surgical procedures were performed from 2015 to 2017 with 13.4% (261) of all procedures ultimately performed for malignancy. Of all breast procedures performed, 95.2% of procedures resulted in a malignant diagnosis. The remaining subtypes of procedures had rates ranging from

Many soil health assessment methods are being developed. However, they often lack assessment of soil-borne diseases. To better address management strategies for soil-borne disease and overall soil and plant health, the concept of Integrated Soil Health Management (ISHM) is explored. Applying the concept of Integrated Pest Management and an agroecological transdisciplinary approach, ISHM offers a framework under which a structure for developing and implementing biointensive soil health management strategies for a particular agroecosystem is defined. As a case study, a history of soil-borne disease management in California strawberries is reviewed and contrasted with a history of arthropod pest management to illustrate challenges associated with soil-borne disease management and the future directions of soil health research and soil-borne disease management. ISHM system consists of comprehensive soil health diagnostics, farmers' location-specific knowledge and adaptability, a suite of soil health management practices, and decision support tools. As we better understand plant-soil-microorganism interactions, including the mechanisms of soil suppressiveness, a range of diagnostic methodologies and indicators and their action thresholds may be developed. These knowledge-intensive and location-specific management systems require transdisciplinary approaches and social learning to be co-developed with stakeholders. The ISHM framework supports research into the broader implications of soil health such as the “One health” concept, which connects soil health to the health of plants, animals, humans, and ecosystems and research on microbiome and nutrient cycling that may better explain these interdependencies.

Multiple studies have established the contamination of hospital sinks and transmission to hospital personnel. Few studies have assessed the contamination and transmission of microorganisms from the faucets of operating bay scrub sinks to operating room (OR) personnel, a potential route of infection for patients. This study aimed to investigate if there was pathogenic contamination of scrub sinks and possible transmission of those pathogens to the hands of OR personnel after preoperative hand disinfection. Swabs were taken from the hands of 50 OR personnel and from the faucets of 24 scrubs sinks at two different hospital sites, and were cultured. Hands were swabbed after completing a surgical hand scrub. Results were reported in colony-forming units per millilitre. There was significant scrub sink contamination with primarily Gram-negative organisms, such as Delftia acidovorans and Sphingomonas paucimobilis. There was no overlap in bacterial species between the cultures from hands and scrub sinks. Cultures from the sinks and the hands of the OR personnel from one site had significantly higher bacterial growth compared with the other site (p

Post-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the function of T cells. The preferential proliferation of NKG2A-positive natural killer (NK) cells during primary symptomatic EBV infection known as infectious mononucleosis (IM) and their reactivity toward EBV-infected B cells point to a role of NK cell in the immune control of EBV. However, NK cell-mediated immune response to EBV in immunosuppressed transplant recipients who develop PTLD remains unclear. In this study, we longitudinally analyzed the phenotype and function of different NK cell subsets in a cohort of pediatric liver transplant patients who develop PTLD and compared them to those of children with IM. We found persistently elevated plasma EBV DNA levels in the PTLD patients indicating suboptimal anti-viral immune control. PTLD patients had markedly decreased frequency of CD56dimNKG2A+Killer Immunoglobulin-like receptor (KIR)− NK cells from the time of diagnosis through remission compared to those of IM patients. Whilst the proliferation of CD56dimNKG2A+KIR− NK cells was diminished in PTLD patients, this NK cell subset maintained its ability to potently degranulate against EBV-infected B cells. Compared to cytomegalovirus (CMV)-seropositive and -negative IM patients, PTLD patients co-infected with CMV and EBV had significantly higher levels of a CMV-associated CD56dimNKG2ChiCD57+NKG2A−KIR+ NK cell subset accumulating at the expense of NKG2A+KIR− NK cells. Taken together, our data indicate that co-infection of CMV and EBV diminishes the frequency of CD56dimNKG2A+KIR− NK cells and contributes to suboptimal control of EBV in immunosuppressed children with PTLD.

Abstract Background Removal of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population. Methods REMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and β-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death. Discussion MCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser. Trial registration Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482. Date of registration - 21/06/2016.

Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.