Exploring Scale and Boundaries in Food System Assessments

The local food movement in the U.S. has permeated popular culture and academia; it has even infiltrated non-profit work, urban and regional planning, and government entities. By its very name, the local food movement binds food activity to a scale – the local – that is nebulous and context dependent. Scale is a crucial part of the discourse and implementation of both local food movement efforts and food studies research – scale is used to conceptualize local food system (LFS) efforts as well as implement them. This thesis explores how scale is operationalized in LFS activities through food system assessments (FSAs), a first step many practitioners take in food system planning efforts. It examines how FSAs employ, construct, and complicate scale in LFS activity and discourse. Through an analysis of eight FSA case studies, including interviews with FSA contributors, three themes emerge: (1) FSAs are a collaborative process that are context dependent and can lead to material and scalar dependent consequences, (2) by using a food system perspective, FSA contributors complicate and call out arbitrary political boundaries and normative definitions of ‘local’ and ‘regional’ that are commonly used to define a food system, and (3) FSA practitioners employ a binary mode of thinking in which the local and global scale are perceived as separate, unrelated entities, and practitioners thus exclude large-scale food system perspectives from their FSAs. This thesis argues for a more nuanced and critical approach to scale in food studies research and food systems practice

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway

Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis

Importance For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain. Objective To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy. Design, Setting, and Participants A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours. Intervention From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care. Main Outcomes and Measures The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected. Results Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, −2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, −0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, −2.07 to 5.45; P = .03). Conclusions and Relevance Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive

Whole-genome sequencing reveals host factors underlying critical COVID-19

: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit:prospective analysis of data from 27 countries

Purpose: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. Methods: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. Results: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10–5.21]; p &lt; 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. Conclusions: We did not identify any survival benefit from critical care admission following surgery

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease