David healy

Precise regulation of Type I interferon signaling is crucial for combating infection and cancer while avoiding autoimmunity. Type I interferon signaling is negatively regulated by USP18. USP18 cleaves ISG15, an interferon-induced ubiquitin-like modification, via its canonical catalytic function, and inhibits Type I interferon receptor activity through its scaffold role. USP18 loss-of-function dramatically impacts immune regulation, pathogen susceptibility, and tumor growth. However, prior studies have reached conflicting conclusions regarding the relative importance of catalytic versus scaffold function...

BACKGROUND: Evidence supports associations between polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and psychosis. However, PUFA trajectories in the general population have not been characterised and associations with psychosis-spectrum outcomes in early adulthood are unknown. background METHODS: Plasma omega-6:omega-3 ratio and DHA %total fatty acids were measured by nuclear magnetic spectroscopy at 7,15,17 and 24years in the Avon Longitudinal Study of Parents and Children...

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores upon cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)1-10 . Here we report that GSDMD Cys191 is S-palmitoylated and palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Surprisingly, cleavage-deficient D275A GSDMD is also palmitoylated after inflammasome stimulation or treatment with ROS activators, and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT...

OBJECTIVES: The authors sought to measure and compare practice preference variation in neonatal respiratory care within and between neonatal intensive care units (NICUs) using the Neonatology Survey of Interdisciplinary Groups in Healthcare Tool (NSIGHT). STUDY DESIGN: Eleven NICUs completed the NSIGHT between 2019 and 2021. Net preference was measured by mean response; agreement was ranked by standard distribution of response values. Heat maps showed comparisons between NICUs and disciplines...

INTRODUCTION: Hospitals and the healthcare system contribute significantly to global warming, due to the energy use, water use and waste produce going directly to landfill. The operating theatre environment contributes to 70% of all hospital waste, and a proportion of this is due to unused surgical supplies, such as those stocked but never used as they go past their use-by date. AIM: To evaluate how use-by dates are identified and assigned to surgical equipment, and if there are opportunities to re-use, or re-sterilise this equipment in order to reduce waste from the operating theatre environment...

Despite the fact that genes and the environment are known to play a central role in islet function, our knowledge of how these parameters interact to modulate insulin secretory function remains relatively poor. Presently, we performed ex vivo glucose-stimulated insulin secretion and insulin content assays in islets of 213 mice from 13 inbred mouse strains on chow, western diet, and ketogenic diet. Strikingly, among these 13 strains, islets from the commonly used C57BL/6J mouse strain were the least glucose responsive...

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18...

Introduction Standard of care management for open fractures historically mandates emergent systemic antibiotic administration, followed by urgent irrigation and debridement in the operating room, regardless of injury severity. However, significant controversy exists regarding the specific implementation and importance of these commonly accepted guidelines. We aimed to define differences in the management of grade 1 open distal radius fractures. Methods An anonymous online survey was distributed to attending surgeon members of either the Orthopaedic Trauma Association (OTA) between January 2019 and April 2019 or the New York Society for Surgery of the Hand (NYSSH) in January 2019...

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels...

IMPORTANCE: It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. OBJECTIVE: To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository...

No abstract text is available yet for this article.

BACKGROUND: Prenatal and perinatal complications are established risk factors for psychotic disorder, but far less is known about these measures and psychotic experiences (PEs). We investigated the longitudinal effect of prenatal risk factors (maternal behavior, medication complications) and perinatal risk factors (birth weight, medical complications) on frequency of PEs. We also examined the cumulative risk of prenatal/perinatal risk factors, and differences between transient PE, persistent PE, and controls...

Large-scale, multi-site collaboration is becoming indispensable for a wide range of research and clinical activities in oncology. To facilitate the next generation of advances in cancer biology, precision oncology and the population sciences it will be necessary to develop and implement data management and analytic tools that empower investigators to reliably and objectively detect, characterize and chronicle the phenotypic and genomic changes that occur during the transformation from the benign to cancerous state and throughout the course of disease progression...

This paper presents a comparative analysis of the sustainability aspects between print and electronic journals. A narrative synthesis is presented under the three key areas of environmental impact, social impact, and impact on research practices. Over the past decades, the gradual transition from print to electronic media has facilitated greater global access to academic research, reshaped research methodologies through innovative tools and systems, and arguably, reduced the ecological footprint of academia...

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754)...

BACKGROUND: Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms. METHODS: We used data from participants of the North American Prodromal Longitudinal Studies (NAPLS) 2 and 3 (n = 715) who provided blood samples (Unaffected Comparison Subjects (UC) n = 223 and CHR n = 483)...

Previously, blood and body fluid exposures were managed by a visit to the University Employee Health Clinic during normal business hours and the Emergency Department after hours. We implemented the "S-T-I-C-K" program where healthcare personnel were evaluated immediately after exposure by a nurse-driven 24/7 hotline. Increasing accessibility to care and a simplified process for exposure management led to a significant decrease in Emergency Department utilization and time between the exposure and receipt of post-exposure prophylaxis...

No abstract text is available yet for this article.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys...

BACKGROUND: To enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group. METHODS: The extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires...