The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.

Aims Presentations of intoxicated patients to hospital are frequent and increasing. We aimed to review the existing evidence that the presence of inpatient clinical toxicology services reduces use of resources without impacting on the care of these patients. Methods We conducted a literature search using the Cochrane Library, PubMed, and Embase for articles that measured length of stay (and other outcomes) for the target population, with toxicology services as an intervention. The articles were reviewed with respect to the ROBINS‐I tool. Results Seven relevant articles were identified. Six of these studies demonstrated reduced hospital length of stay for intoxicated patients in hospitals with inpatient toxicology services. None of the articles demonstrated a detriment in morbidity or mortality. There were also improvements in other resource‐related outcomes. Conclusions The presence of inpatient toxicology services appears to improve resource utilization, in reduction of length of stay, as well as a number of other related outcomes. It does this without compromising on patient morbidity or mortality. Thus, it should be considered as a potential model of care for future toxicology services, especially with current trends of increasing demand for service efficiency.

Aim:The North Queensland region of Australia has a high incidence of pediatric thoracic empyema (pTE). We describe the management of empyema at the Townsville University Hospital which is the regional referral center for these children. The impact of a newly developed institutional guideline is also discussed. Methods: This retrospective audit included children under the age of 16 years treated for empyema between 1 Jan 2007 and 31 December 2018. Demographic and management-related variables were correlated to outcomes. A local guideline was introduced at the beginning of 2017 and patient outcomes characteristics pre, and post introduction of this guideline are compared. Results: There were 153 children with pTE (123 before and 30 after the introduction of a local guideline). Nonsurgical management was associated with a higher treatment failure rate. Median length of stay (LOS) was 11.8 (IQR 9.3-16) days. Longer hospital LOS was associated with younger age (r 2 −0.16, P = 0.04), Aboriginal and/or Torres Strait (ATSI) ancestry (13.8 vs. 10.5 days, P = 0.002) and concomitant respiratory viral infections (14.4 vs. 10.9 days, P = 0.003). The introduction of local guideline was associated with significant decrease in the use of empirical chest CT scans (54.4% before vs. 6.7% after, P < 0.001) and duration of intravenous antibiotics (14 days before vs. 10 days after, P = 0.02). There was no significant change in the hospital LOS (12.1 days pre and 11.7 post, P = 0.8). Conclusions: Younger age, concomitant viral respiratory infections and ATSI ancestry were identified as potential risk factors for increase LOS. Hospital LOS following the adoption of an institutional guideline was unchanged. However, such a guideline may identify populations at risk for an unfavorable course and avoid unnecessary antibiotic treatment and radiation exposure.