Clinical applications of remote ischaemic preconditioning in native and transplant acute kidney injury

Ischaemia-reperfusion (IR) injury is a composite of the injury sustained during a period of reduced or absent blood flow to a tissue or organ and the additional insult sustained upon reperfusion that limits the amount of tissue that can be salvaged. IR injury plays a central role in both native and transplant acute kidney injury (AKI). Native AKI is associated with increased morbidity and mortality in hospital inpatients, and transplant AKI contributes to graft dysfunction, ultimately limiting graft longevity. In this review, we discuss the potential therapeutic benefits of a cost-effective and low-risk intervention, remote ischaemic preconditioning (RIPC), and its applicability in the prevention and reduction of AKI

Comparative performance of rural water supplies during drought

As rural African communities experience more frequent and extreme droughts, it is increasingly important that water supplies are climate resilient. Using a unique temporal dataset we explore rural water supply (n = 5196) performance during the 2015–16 drought in Ethiopia. Mean functionality ranged from 60% for motorised boreholes to 75% for hand-pumped boreholes. Real-time monitoring and responsive operation and maintenance led to rapid increases in functionality of hand-pumped and, to a lesser extent, motorised boreholes. Increased demand was placed on motorised boreholes in lowland areas as springs, hand-dug-wells and open sources failed. Most users travelled >1 h to access motorised boreholes but 30 m) groundwater performed best during the drought. Prioritising access to groundwater via multiple improved sources and a portfolio of technologies, such as hand-pumped and motorised boreholes, supported by responsive and proactive operation and maintenance, increases rural water supply resilience

Exploring the Concept of Healing Spaces

DOI:10.1177/193758671668056

Flipping the odds of drug development success through human genomics

Drug development depends on accurately identifying molecular targets that both play a causal role in a disease and are amenable to pharmacological action by small molecule drugs or bio-therapeutics, such as monoclonal antibodies. Errors in drug target specification contribute to the extremely high rates of drug development failure. Integrating knowledge of genes that encode druggable targets with those that influence susceptibility to common disease has the potential to radically improve the probability of drug development success

Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled, proof-of-concept trial

This is the peer reviewed version of the following article: Hobbs AJ, Moyes AJ, Baliga RS, et al. Neprilysin inhibition for pulmonary arterial hypertension: a randomized, double‐blind, placebo‐controlled, proof‐of‐concept trial. Br J Pharmacol. 2019. https://doi.org/10.1111/bph.14621, which has been published in final form at https://doi.org/10.1111/bph.14621. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThis work was supported by a British Heart Foundation Project Grant (PG/11/88/28992) and the National Institutes for Health Research, Comprehensive Biomedical Research Centre award to UC

COVID-19 in Pregnancy in Scotland (COPS):protocol for an observational study using linked Scottish national data

Funding: EAVE II funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DG Health and Social Care. COPS receive additional funding from Tommy’s charity (1060508; SC039280). SJS is supported by Wellcome Trust (209560/Z/17/Z).Introduction The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19. Methods and analysis Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes. Ethics and dissemination COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.Publisher PDFPeer reviewe

The CRESST Dark Matter Search

The current status of CRESST (Cryogenic Rare Event Search using Superconducting Thermometers) and new results concerning the detector development are presented. The basic technique of CRESST is to search for particle Dark Matter (WIMPS, Weakly Interacting Massive particles) by the measurement of non-thermal phonons as created by WIMP-induced nuclear recoils. Combined with the newly developed method of simultaneous measurement of scintillation light, strong background discrimination is possible, resulting in a substantial increase in WIMP detection sensitivity. The short and long term perspectives of CRESST are discussed.Comment: 12 pages, 6 figure

Characterisation of leukocytes in a human skin blister model of acute inflammation and resolution.

There is an increasing need to understand the leukocytes and soluble mediators that drive acute inflammation and bring about its resolution in humans. We therefore carried out an extensive characterisation of the cantharidin skin blister model in healthy male volunteers. A novel fluorescence staining protocol was designed and implemented, which facilitated the identification of cell populations by flow cytometry. We observed that at the onset phase, 24 h after blister formation, the predominant cells were CD16hi/CD66b+ PMNs followed by HLA-DR+/CD14+ monocytes/macrophages, CD11c+ and CD141+ dendritic cells as well as Siglec-8+ eosinophils. CD3+ T cells, CD19+ B cells and CD56+ NK cells were also present, but in comparatively fewer numbers. During resolution, 72 h following blister induction, numbers of PMNs declined whilst the numbers of monocyte/macrophages remain unchanged, though they upregulated expression of CD16 and CD163. In contrast, the overall numbers of dendritic cells and Siglec-8+ eosinophils increased. Post hoc analysis of these data revealed that of the inflammatory cytokines measured, TNF-α but not IL-1β or IL-8 correlated with increased PMN numbers at the onset. Volunteers with the greatest PMN infiltration at onset displayed the fastest clearance rates for these cells at resolution. Collectively, these data provide insight into the cells that occupy acute resolving blister in humans, the soluble mediators that may control their influx as well as the phenotype of mononuclear phagocytes that predominate the resolution phase. Further use of this model will improve our understanding of the evolution and resolution of inflammation in humans, how defects in these over-lapping pathways may contribute to the variability in disease longevity/chronicity, and lends itself to the screen of putative anti-inflammatory or pro-resolution therapies

Resistant Hypertension Trials and Tribulations

Introduction Our case concerns a 62-year-old white woman who was referred by her general practitioner in 2012 with a long-standing history of difficult to control blood pressure (BP). She had significant past medical history including an excised meningioma and an implantable cardiac defibrillator for a single episode of polymorphic ventricular tachycardia during general anesthesia. She also had a possible diagnosis of epilepsy and tablet-controlled type-2 diabetes mellitus. On referral to our clinic she was on 5 antihypertensive medications including enalapril 40 mg daily, bisoprolol 10 mg daily, lercanidipine 10 mg daily, losartan 50 mg daily, and indapamide 2.5 mg once daily. She was also on metformin and sodium valproate. In clinic, she appeared well. She complained of occasional headaches but had no other symptom of note. She had no significant family history of high BP. On examination, she had a body mass index in the normal range and after repeated measures, her clinic BP was found to be 195/110 mm Hg. There was very little else to find on examination, including no murmurs or renal bruits. On fundoscopy, she had grade 2 hypertensive retinopathy. Baseline investigations did not reveal anything untoward. She had a normal blood count, renal function, and electrolytes. On urinalysis, she had mild proteinuria, with a urine protein-creatinine ratio of 17 (laboratory reference value 0–13 mg/mmol). Her ECG showed sinus rhythm with a normal rate, axis, and voltage. Her echocardiogram did not show any evidence of left ventricular hypertrophy, left ventricular ejection fraction was 58%, and she had evidence of mild diastolic dysfunction. Ambulatory BP monitoring (ABPM) was performed and her mean 24-hour BP was 190/105 mm Hg. The range was 118/67 to 227/127 mm Hg, with >90% of readings >140/90 mm Hg. So, here, we have a patient with a diagnosis of resistant hypertension according to the definition in the European guidelines