What does "good" community and public engagement look like? Developing relationships with community members in global health research

Community and public engagement (CPE) is increasingly becoming a key component in global health research. The National Institute for Health Research (NIHR) is one of the leading funders in the UK of global health research and requires a robust CPE element in the research it funds, along with CPE monitoring and evaluation. But what does "good" CPE look like? And what factors facilitate or inhibit good CPE? Addressing these questions would help ensure clarity of expectations of award holders, and inform effective monitoring frameworks and the development of guidance. The work reported upon here builds on existing guidance and is a first step in trying to identify the key components of what "good" CPE looks like, which can be used for all approaches to global health research and in a range of different settings and contexts. This article draws on data collected as part of an evaluation of CPE by 53 NIHR-funded award holders to provide insights on CPE practice in global health research. This data was then debated, developed and refined by a group of researchers, CPE specialists and public contributors to explore what "good" CPE looks like, and the barriers and facilitators to good CPE. A key finding was the importance, for some research, of investing in and developing long term relationships with communities, perhaps beyond the life cycle of a project; this was regarded as crucial to the development of trust, addressing power differentials and ensuring the legacy of the research was of benefit to the community. [Abstract copyright: Copyright © 2022 Hickey, Porter, Tembo, Rennard, Tholanah, Beresford, Chandler, Chimbari, Coldham, Dikomitis, Dziro, Ekiikina, Khattak, Montenegro, Mumba, Musesengwa, Nelson, Nhunzvi, Ramirez and Staniszewska.

High-resolution mass models of dwarf galaxies from LITTLE THINGS

We present high-resolution rotation curves and mass models of 26 dwarf galaxies from LITTLE THINGS. LITTLE THINGS is a high-resolution Very Large Array HI survey for nearby dwarf galaxies in the local volume within 11 Mpc. The rotation curves of the sample galaxies derived in a homogeneous and consistent manner are combined with Spitzer archival 3.6 micron and ancillary optical U, B, and V images to construct mass models of the galaxies. We decompose the rotation curves in terms of the dynamical contributions by baryons and dark matter halos, and compare the latter with those of dwarf galaxies from THINGS as well as Lambda CDM SPH simulations in which the effect of baryonic feedback processes is included. Being generally consistent with THINGS and simulated dwarf galaxies, most of the LITTLE THINGS sample galaxies show a linear increase of the rotation curve in their inner regions, which gives shallower logarithmic inner slopes alpha of their dark matter density profiles. The mean value of the slopes of the 26 LITTLE THINGS dwarf galaxies is alpha =-0.32 +/- 0.24 which is in accordance with the previous results found for low surface brightness galaxies (alpha = -0.2 +/- 0.2) as well as the seven THINGS dwarf galaxies (alpha =-0.29 +/- 0.07). However, this significantly deviates from the cusp-like dark matter distribution predicted by dark-matter-only Lambda CDM simulations. Instead our results are more in line with the shallower slopes found in the Lambda CDM SPH simulations of dwarf galaxies in which the effect of baryonic feedback processes is included. In addition, we discuss the central dark matter distribution of DDO 210 whose stellar mass is relatively low in our sample to examine the scenario of inefficient supernova feedback in low mass dwarf galaxies predicted from recent Lambda SPH simulations of dwarf galaxies where central cusps still remain.Peer reviewe

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Risk factors for preoperative periventricular leukomalacia in term neonates with hypoplastic left heart syndrome are patient related

BackgroundPreoperative brain injury is common in neonates with complex congenital heart disease. Increasing evidence suggests a complex interaction of prenatal and postnatal risk factors for development of brain white matter injury, called periventricular leukomalacia (PVL), in neonates with complex congenital heart disease. To date, there remains a limited understanding of the risk factors contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS).MethodsNeonates with HLHS or HLHS variants from 3 prospective magnetic resonance imaging studies (2003-2010) were selected for this cohort. Preoperative brain magnetic resonance imaging was performed the morning of the surgery. Stepwise multilogistic regression of patient characteristics, mode of delivery (cesarean section vs vaginal), time of diagnosis (prenatal vs postnatal), HLHS subtypes, brain total maturation score, time to surgery, individual averaged daily preoperative blood gases, and complete blood cell count values was used to determine significant associations.ResultsA total of 57 neonates with HLHS were born at 38.7 ± 2.3 weeks; 86% (49/57) had a prenatal diagnosis, with 31% (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common in this cohort, 71% (41/57). Preoperative PVL was identified in 19% (11/57). Male patients with AA (P = .004) were at higher risk for PVL. Lower total brain maturation score was also identified as a strong predictor for preoperative PVL (P = .005).ConclusionsIn neonates with HLHS, nonmodifiable patient-related factors, including male sex with AA (lack of antegrade blood flow) and lower total brain maturation score, placed neonates at the greatest risk for preoperative white matter injury