Saturated: a study in fat obsession

This thesis examines both contemporary and historical meanings surrounding human body FAT in order to illuminate, chiefly, the forces that have rendered it both an omnipresent and negative entity in Western societies. It explores the apparent contradiction that we must exist amidst hyper-consumptive capitalism yet display no bodily evidence of such consumption. Along with an investigation into alternative bodily conceptions to that of the hegemonic West, a discourse analysis is employed to challenge the key assumptions that underpin the current 'obesity epidemic' and its ensuing 'war on obesity' so that body FAT may be configured differently. It is shown that, because bodily conceptions and ideals are complex cultural constructions, body FAT, as a substance, is not the scourge it is presently portrayed, but rather a substance that signifies most of what consumer society despises and fears. It is argued that the 'war on obesity' has not been successful, and will continue to be ineffective, because the focus should not be on losing body FAT but rather on the conditions of poverty that generate overall ill-health. It is concluded that such a 'war', if sustained in its current fashion, will only serve to further malign the situations of those deemed 'overweight and obese'

Preventing child pedestrian injuries and deaths arising from vehicle-child accidents in domestic driveways: An action research project

This research was a three-fold investigation into the viability of previous recommendations for vehicle-related child driveway accident safety . Firstly, the groups most at risk of these types of accidents were determined in order that they could be specifically considered when reviewing the practicalities of previous recommendations . Secondly, the feasibility of previous recommendations was systematically examined through both an extensive literature review and key and expert informant interviews . Based on these, the likelihood of implementation of previous safety recommendations for the identified high risk groups was ascertained, providing a basis on which to abandon some previous recommendations, remove obstacles to others which would enhance practicability and generate further recommendations that would be tenable for the at-risk groups in particular. The key findings of this research were, foremost, that there is a noticeable lack of specific reference to vehicle-related child driveway accidents in any legislation or safety guidelines, as well as a shortage of official data that deal expressly with this type of accident. Further, it was found that the major obstacles to the implementation of previous recommendations - particularly the environmental ones - were cost, autonomy, and spatial constraints. While several recommendations were abandoned due to factors such as unproven or dubious effectiveness and/or prohibitive cost, it was found that the most viable recommendations were characterised by their relatively low cost for the families involved. These recommendations were typically environmental or educational in nature. Thus, the recommendations in this report include some moderate regulatory changes to facilitate greater uptake of environmental and behaviour-modifying recommendations as well as practical ideas that all need to be part of a cohesive campaign to address the issue of vehicle-related child driveway accidents in New Zealand

Optimising child accident research outcomes: An action research project on maximising the dissemination and implementation of the Summer Research Scholarship Project reports and recommendations of the Child Accident Prevention Foundation of New Zealand

A key objective of the Child Accident Prevention Foundation of New Zealand (hereafter referred to as "CAPFNZ" or "the Foundation") is to reduce the incidence and severity of child accidents. The reports and recommendations that arise from the Foundation's Summer Research Scholarship (SRS) projects have the potential to be a major means to achieving this end. The purpose of this research was to investigate the extent to which the SRS projects were achieving that objective, by assessing the degree to which CAPFNZ SRS reports and especially their recommendations are currently in the public domain. The research also identified the current barriers or obstacles to dissemination, and determined cost-effective ways in which dissemination and implementation of these reports and their findings could be enhanced. Our proposal foreshadowed the prospect of this project yielding a demonstration website as one approach to achieving a more effective distribution of CAPFNZ SRS reports and related material

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570