High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?

A high prevalence of hepatic pathology (in 17 of 19 cases) was reported in post-mortem (PM) examinations of COVID-19 patients, undertaken between March 2020 and February 2021 by a single autopsy pathologist in two English Coronial jurisdictions. The patients in our cohort demonstrated high levels of recognised COVID-19 risk factors, including hypertension (8/16, 50%), type 2 diabetes mellitus (8/16, 50%) and evidence of arteriopathy 6/16 (38%). Hepatic abnormalities included steatosis (12/19; 63%), moderate to severe venous congestion (5/19; 26%) and cirrhosis (4/19; 21%). A subsequent literature review indicated a significantly increased prevalence of steatosis (49%), venous congestion (34%) and cirrhosis (9.3%) in COVID-19 PM cases, compared with a pre-pandemic PM cohort (33%, 16%, and 2.6%, respectively), likely reflecting an increased mortality risk in SARS-CoV-2 infection for patients with pre-existing liver disease. To corroborate this observation, we retrospectively analysed the admission liver function test (LFT) results of 276 consecutive, anonymised COVID-19 hospital patients in our centre, for whom outcome data were available. Of these patients, 236 (85.5%) had significantly reduced albumin levels at the time of admission to hospital, which was likely indicative of pre-existing chronic liver or renal disease. There was a strong correlation between patient outcome (length of hospital admission or death) and abnormal albumin at the time of hospital admission (p = 0.000012). We discuss potential mechanisms by which our observations of hepatic dysfunction are linked to a risk of COVID-19 mortality, speculating on the importance of recently identified anti-interferon antibodies

School-based education programmes for the prevention of unintentional injuries in children and young people.

Background: Unintentional injuries are the leading cause of death in children aged four to 18 years and are a major cause of ill health. The school setting offers the opportunity to deliver preventive interventions to a large number of children and has been used to address a range of public health problems. However, the effectiveness of the school setting for the prevention of different injury mechanisms in school-aged children is not well understood. Objectives: To assess the effects of school-based educational programmes for the prevention of injuries in children and evaluate their impact on improving children's safety skills, behaviour and practices, and knowledge, and assess their cost-effectiveness. Search methods: We ran the most recent searches up to 16 September 2016 for the following electronic databases: Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials; Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R); Embase and Embase Classic (Ovid); ISI Web of Science: Science Citation Index Expanded; ISI Web of Science Conference Proceedings Citation Index-Science; ISI Web of Science: Social Sciences Citation Index; ISI Web of Science: Conference Proceedings Citation Index - Social Sciences & Humanities; and the 14 October 2016 for the following electronic databases: Health Economics Evaluations Database (HEED); Health Technology Assessment Database (HTA); CINAHL Plus (EBSCO); ZETOC; LILACS; PsycINFO; ERIC; Dissertation Abstracts Online; IBSS; BEI; ASSIA; CSA Sociological Abstracts; Injury Prevention Web; SafetyLit; EconLit (US); PAIS; UK Clinical Research Network Study Portfolio; Open Grey; Index to Theses in the UK and Ireland; Bibliomap and TRoPHI. Selection criteria: We included randomised controlled trials (RCTs), non-randomised controlled trials (non-RCTs), and controlled before-and-after (CBA) studies that evaluated school-based educational programmes aimed at preventing a range of injury mechanisms. The primary outcome was self-reported or medically attended unintentional (or unspecified intent) injuries and secondary outcomes were observed safety skills, observed behaviour, self-reported behaviour and safety practices, safety knowledge, and health economic outcomes. The control groups received no intervention, a delayed injury-prevention intervention or alternative school-based curricular activities. We included studies that aimed interventions at primary or secondary prevention of injuries from more than one injury mechanism and were delivered, in part or in full, in schools catering for children aged four to 18 years. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two review authors identified relevant trials from title and abstracts of studies identified in searches and two review authors extracted data from the included studies and assessed risk of bias. We grouped different types of interventions according to the outcome assessed and the injury mechanism targeted. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies. Main results: The review included 27 studies reported in 30 articles. The studies had 73,557 participants with 12 studies from the US; four from China; two from each of Australia, Canada, the Netherlands and the UK; and one from each of Israel, Greece and Brazil. Thirteen studies were RCTs, six were non-RCTs and eight were CBAs. Of the included studies, 18 provided some element of the intervention in children aged four to 11 years, 17 studies included children aged 11 to 14 years and nine studies included children aged 14 to 18 years. The overall quality of the results was poor, with the all studies assessed as being at high or unclear risks of bias across multiple domains, and varied interventions and data collection methods employed. Interventions comprised information-giving, peer education or were multi-component. Seven studies reported the primary outcome of injury occurrence and only three of these were similar enough to combine in a meta-analysis, with a pooled incidence rate ratio of 0.73 (95% confidence interval (CI) 0.49 to 1.08; 2073 children) and substantial statistical heterogeneity (I2 = 63%). However, this body of evidence was low certainty, due to concerns over this heterogeneity (inconsistency) and imprecision. This heterogeneity may be explained by the non-RCT study design of one of the studies, as a sensitivity analysis with this study removed found stronger evidence of an effect and no heterogeneity (I2 = 0%). Two studies report an improvement in safety skills in the intervention group. Likewise, the four studies measuring observed safety behaviour reported an improvement in the intervention group relative to the control. Thirteen out of 19 studies describing self-reported behaviour and safety practices showed improvements, and of the 21 studies assessing changes in safety knowledge, 19 reported an improvement in at least one question domain in the intervention compared to the control group. However, we were unable to pool data for our secondary outcomes, so our conclusions were limited, as they were drawn from highly diverse single studies and the body of evidence was low (safety skills) or very low (behaviour, safety knowledge) certainty. Only one study reported intervention costs but did not undertake a full economic evaluation (very low certainty evidence). Authors' conclusions: There is insufficient evidence to determine whether school-based educational programmes can prevent unintentional injuries. More high-quality studies are needed to evaluate the impact of educational programmes on injury occurrence. There is some weak evidence that such programmes improve safety skills, behaviour/practices and knowledge, although the evidence was of low or very low quality certainty. We found insufficient economic studies to assess cost-effectiveness

School-based education programmes for the prevention of unintentional injuries in children and young people.

Background: Unintentional injuries are the leading cause of death in children aged four to 18 years and are a major cause of ill health. The school setting offers the opportunity to deliver preventive interventions to a large number of children and has been used to address a range of public health problems. However, the effectiveness of the school setting for the prevention of different injury mechanisms in school-aged children is not well understood. Objectives: To assess the effects of school-based educational programmes for the prevention of injuries in children and evaluate their impact on improving children's safety skills, behaviour and practices, and knowledge, and assess their cost-effectiveness. Search methods: We ran the most recent searches up to 16 September 2016 for the following electronic databases: Cochrane Injuries Group Specialised Register; Cochrane Central Register of Controlled Trials; Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations; Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R); Embase and Embase Classic (Ovid); ISI Web of Science: Science Citation Index Expanded; ISI Web of Science Conference Proceedings Citation Index-Science; ISI Web of Science: Social Sciences Citation Index; ISI Web of Science: Conference Proceedings Citation Index - Social Sciences & Humanities; and the 14 October 2016 for the following electronic databases: Health Economics Evaluations Database (HEED); Health Technology Assessment Database (HTA); CINAHL Plus (EBSCO); ZETOC; LILACS; PsycINFO; ERIC; Dissertation Abstracts Online; IBSS; BEI; ASSIA; CSA Sociological Abstracts; Injury Prevention Web; SafetyLit; EconLit (US); PAIS; UK Clinical Research Network Study Portfolio; Open Grey; Index to Theses in the UK and Ireland; Bibliomap and TRoPHI. Selection criteria: We included randomised controlled trials (RCTs), non-randomised controlled trials (non-RCTs), and controlled before-and-after (CBA) studies that evaluated school-based educational programmes aimed at preventing a range of injury mechanisms. The primary outcome was self-reported or medically attended unintentional (or unspecified intent) injuries and secondary outcomes were observed safety skills, observed behaviour, self-reported behaviour and safety practices, safety knowledge, and health economic outcomes. The control groups received no intervention, a delayed injury-prevention intervention or alternative school-based curricular activities. We included studies that aimed interventions at primary or secondary prevention of injuries from more than one injury mechanism and were delivered, in part or in full, in schools catering for children aged four to 18 years. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Two review authors identified relevant trials from title and abstracts of studies identified in searches and two review authors extracted data from the included studies and assessed risk of bias. We grouped different types of interventions according to the outcome assessed and the injury mechanism targeted. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies. Main results: The review included 27 studies reported in 30 articles. The studies had 73,557 participants with 12 studies from the US; four from China; two from each of Australia, Canada, the Netherlands and the UK; and one from each of Israel, Greece and Brazil. Thirteen studies were RCTs, six were non-RCTs and eight were CBAs. Of the included studies, 18 provided some element of the intervention in children aged four to 11 years, 17 studies included children aged 11 to 14 years and nine studies included children aged 14 to 18 years. The overall quality of the results was poor, with the all studies assessed as being at high or unclear risks of bias across multiple domains, and varied interventions and data collection methods employed. Interventions comprised information-giving, peer education or were multi-component. Seven studies reported the primary outcome of injury occurrence and only three of these were similar enough to combine in a meta-analysis, with a pooled incidence rate ratio of 0.73 (95% confidence interval (CI) 0.49 to 1.08; 2073 children) and substantial statistical heterogeneity (I2 = 63%). However, this body of evidence was low certainty, due to concerns over this heterogeneity (inconsistency) and imprecision. This heterogeneity may be explained by the non-RCT study design of one of the studies, as a sensitivity analysis with this study removed found stronger evidence of an effect and no heterogeneity (I2 = 0%). Two studies report an improvement in safety skills in the intervention group. Likewise, the four studies measuring observed safety behaviour reported an improvement in the intervention group relative to the control. Thirteen out of 19 studies describing self-reported behaviour and safety practices showed improvements, and of the 21 studies assessing changes in safety knowledge, 19 reported an improvement in at least one question domain in the intervention compared to the control group. However, we were unable to pool data for our secondary outcomes, so our conclusions were limited, as they were drawn from highly diverse single studies and the body of evidence was low (safety skills) or very low (behaviour, safety knowledge) certainty. Only one study reported intervention costs but did not undertake a full economic evaluation (very low certainty evidence). Authors' conclusions: There is insufficient evidence to determine whether school-based educational programmes can prevent unintentional injuries. More high-quality studies are needed to evaluate the impact of educational programmes on injury occurrence. There is some weak evidence that such programmes improve safety skills, behaviour/practices and knowledge, although the evidence was of low or very low quality certainty. We found insufficient economic studies to assess cost-effectiveness

Insight into Sam Francis’ painting techniques through the analytical study of twenty-eight artworks made between 1946 and 1992

The present paper proposes an overview of the painting materials experimented with over the years by Sam Francis, leading figure of the post-World War II American painting, through the analytical study of an extended number of paint samples supplied by the Sam Francis Foundation. In total, 279 samples taken from twenty-eight artworks made between 1946 and 1992, were analyzed by Raman, FTIR and Py–GC/MS techniques. The obtained results revealed the Francis’ preference in terms of pigments, i.e., phthalocyanine blues and greens, and outlined unconventional combination of binder media

Spatiotemporal immune zonation of the human kidney.

Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.St Baldrick's Foundation (Robert J Arceci International Award to S.B.). Additional funding was received from the Wellcome Trust (S.B.: 110104/Z/15/Z; M.H.: 107931/Z/15/Z; studentships to B.J.S., G.C., A.M.R., and C.G.). Kidney cancer bio-sampling was funded by core infrastructural funding from the Cambridge Biomedical Research Campus (CBRC) and Cancer Research UK Cambridge Centre. Additional funding in support of individual authors was provided as follows: B.J.S (CRUK predoctoral bursary, C63442/A25230); M.R.C. (CBRC; NIHR Blood and Transplant Research Unit, RG75628; MRC New Investigator Research Grant, MR/N024907/1; Arthritis Research UK Cure Challenge Research Grant, 21777; NIHR Research Professorship RP-2017-08-ST2-002); M.H. (The Lister Institute for Preventative Medicine; NIHR and Newcastle-Biomedical Research Centre); A.F. (ISAC SRL-EL program); S.Lis, S.Lin. (joint Wellcome Trust/MRC, 099175/Z/12/Z); K.W.L (Kidney Research UK Clinical Training Fellowship, TF_013_20171124). R.V-T is supported by an EMBO Long-Term Fellowship and a Human Frontier Science Progra