De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.

The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) "Linked-Read" technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations

Arthritis and disability

Executive summary: Arthritis Australia commissioned the Social Policy Research Centre (SPRC) at UNSW Australia to carry out research on the lived experience of people with arthritis related conditions. This report outlines the methods, findings and implications of the research. Arthritis is the second leading cause of disability and the most common cause of chronic pain in Australia; it is the most prevalent long-term health condition, affecting 3 million people or about 15 per cent of the population. Studies are available on the health costs and loss of productivity associated with arthritis, but not as much is understood about the extent to which arthritis is associated with disability–who is affected, how people are affected, what helps people cope with their condition day to day, and how support services can be improved. Improving understanding of the disability impact of arthritis is particularly important given the transition in Australia to the National Disability Insurance Scheme and the impact this may have on service availability and delivery

The Effects of Prenatal Cannabis Exposure on the Basolateral Amygdala

Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), glutamate/GABA molecular markers. These result in outward pathological behavioural manifestations with males exhibiting enhanced anxiety and both sexes exhibiting cognitive deficits. Given the role of the BLA, it is necessary to mechanistically explore the effect of PCE on the BLA. The present study characterized the interconnected pathophenotype of the BLA-MCL circuit using behavioural, electrophysiological, molecular, and mechanistic assays. Pregnant Wistar rats were assigned to VEH (n=10 dams; n=4 progeny/sex/dam) or 3mg/kg THC (daily, i.p.; n=10 dams; n=4 progeny/sex/dam) from gestational day (GD) 7 to GD22. A subset of progeny (n=8/treatment/sex) were sacrificed on PD21 for molecular assays of the NAc and BLA. Between PD70-85, a subset of progeny (n=20/treatment/sex) were assessed for anxiety, depression, prepulse inhibition, and contextual fear. Between PD90-120, in vivo electrophysiology was used to assess VTA DA-ergic neurons, glutamate, and GABA neurons in the posterior/anterior BLA, and NAc GABA neurons. On PD120, remaining offspring were sacrificed and NAc and BLA punchouts were obtained for molecular assays. A behaviour naïve subset (n=10/sex/treatment) received intra-BLA cannulations for mechanistic assays between PD90-120. In line with previous results, males exhibit a significant anxiogenic phenotype; however, males also exhibited significantly less freezing, suggesting a deficit in contextual fear learning, consistent with significant increases in GAD67 expression; males also exhibit increases in D1R and GABAARα1. Female progeny did not exhibit any outward pathology but did exhibit significantly greater expression of vGLUT2, GABAARα1, and GABAARɣ2. Disturbances in dopaminergic, glutamatergic, and GABAergic electrophysiological activity were also observed in the male progeny within the VTA-BLA-NAc circuit, but not in the female progeny. These suggest that the anxiogenic deficits observed in males are likely contingent on BLA disruptions, while the female progeny is protected from BLA-dependant etiology. Mechanistic assays are currently ongoing

Reducing Indwelling Urinary Catheter Days: Improving Interdisciplinary Communication in a Surgical Intensive Care Unit

Problem Urinary catheter nurse-driven removal protocols (UCNDRPs) are evidence-based algorithms that promote the timely removal of indwelling urinary catheters (IUCs) and prevent catheter-associated urinary tract infections (CAUTIs). Communication barriers hinder consistent implementation of the UCNDRP, resulting in delayed IUC removal and increased risk of CAUTIs. Context This quality improvement project was conducted in a 16-bed surgical intensive care unit (SICU) in an academic medical center in the San Francisco metropolitan area. Interventions Urinary catheter reminder posters displaying the duration of IUC days were placed at the bedside to prompt interdisciplinary communication about IUC indication and removal. An email detailing the project’s background was sent to nurses and physicians by the unit director. One-on-one conversations describing the use of the posters were conducted with bedside nurses. Stickers with an image of an IUC accompanied by the question “Why am I here?” were distributed as light-hearted conversation starters to initiate discussion about IUCs. Measures Interdisciplinary rounds were observed pre- and post-implementation to determine the number of rounds in which the care team discussed IUC indication or removal. The catheter utilization ratio was compared between the pre- and post-intervention periods. Results The frequency of interdisciplinary rounds discussing IUC indication or removal increased by 7% from 23% to 30%. The catheter utilization ratio decreased by 20% from 0.61 in April 2023 to an average of 0.50 from April 1-21, 2024. Conclusion These findings suggest that promoting interdisciplinary communication through visual cues enhances communication and reduces IUC utilization. Further evaluation is needed to ascertain sustainability and long-term impact

Examining Processes of Change for Experientially Distant and Experientially Engaged Client Subgroups in Experiential Therapy for Depression

This study examined whether different client subgroups, identified as either experientially distant or experientially engaged based on their early tendency to approach inner experience, undergo distinct emotional change processes during experiential therapy for depression. It was hypothesized that these distinct emotional change processes would be best captured using different process measures, which were the Experiencing Scale (EXP) and the Classification of Affective Meaning States (CAMS), respectively. As experientially distant clients were hypothesized to experience depression related to being estranged from the adaptive information within emotional experience, increasing general access to emotional experience was presumed to be the change process most likely to relieve their depression, and optimally captured by the EXP scale. Experientially engaged clients were hypothesized to experience depression related to activation of maladaptive emotion schemes, and it was assumed that alleviation of their depression would occur through accessing primary adaptive emotions, which would be measured by the CAMS. A second purpose of this investigation was to examine whether these different change processes would differentially predict long-term resilient gains in addition to outcome at treatment termination. Results opposite to the hypotheses were found. Emotion scheme typology as measured by the CAMS was a better predictor of outcome for the experientially distant subgroup, and depth of experiencing as captured by the EXP scale a better predictor of outcome for the experientially engaged subgroup. While unexpected, these results support the original hypothesis concerning the existence of distinct subtypes of depressed clients who undergo separate paths to change. They also supported experiential therapy change principles, indicating that both depth of experiencing and emotion scheme typology are powerfully related to termination and long-term outcome in this psychotherapy model

The Natural Environment and local perceptions of poverty, well-being and justice in a Mexican fishing community. Gaps and bridges between local perceptions and national metrics

Although the ‘right to enjoy a healthy environment’ is granted by the Mexican Law of Social Development, the environmental dimension is missing in the current national measures of multidimensional poverty. This doctoral research aims to understand the implications of this absence by understanding the local meanings, perceptions and lived experiences of poverty; what contributes to a flourishing, worth-lived life and justice; and the nexus between the natural environment. For this purpose, an integrated ‘Justice and well-being pipeline’ conceptual framework, inspired in the capabilities approach, was designed to examine in a holistic way the processes contributing to shape the dynamics of social exclusion. Research was undertaken in the municipality of San Felipe, a fishing community of Yucatán, México between summer 2016 and spring 2017. The research adopted a mixed data collection and analytical methods including Q-methodology and network analysis. A geographically systematic sampling approach was used to collected data through semi-structured interviews and purposive sampling for Q methodology. Research findings suggest that the absence of national indicators to measure progress towards the social right to a healthy environment hides the detrimental and corrosive effects of an unhealthy environment and the disproportionate negative effect on vulnerable groups, especially low-income, the elderly and those who do not benefit from social protection mechanisms provided by the community. Understanding social exclusion dynamics emanating from the experience of environmental injustice is essential to understand the processes that perpetuate social disadvantage. The empirical research provides evidence of the centrality of the natural environment as an enabler of a wide array of valuable life functionings. Based on this evidence, the thesis proposes a hybrid approach that encompasses the incorporation of a set of Environmental Primary Goods (EPGs) within the current multidimensional poverty measure and the creation of an environmental enabling conditions dashboard focusing on making visible key environmental enabling conditions.The financial support that made possible this dissertation include the CONACYT Cambridge Trust, the Mexican SEP Complementary Scholarship, the Cambridge Political Economy Society Trust (CPEST), and Churchill College support including the Pannett Fund. The fieldwork in Mexico was possible thanks to the University Fieldwork Fund and the Tim & Wendy Whitmore Fund

A comparison of continuous and bi-level positive airway pressure non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis

INTRODUCTION: We conducted the present study to investigate the potential beneficial and adverse effects of continuous positive airway pressure (CPAP) compared with bi-level positive airway pressure (BiPAP) noninvasive ventilation in patients with cardiogenic pulmonary oedema. METHOD: We included randomized controlled studies comparing CPAP and BiPAP treatment in patients with cardiogenic pulmonary oedema from the Cochrane Controlled Trials Register (2005 issue 3), and EMBASE and MEDLINE databases (1966 to 1 December 2005), without language restriction. Two reviewers reviewed the quality of the studies and independently performed data extraction. RESULTS: Seven randomized controlled studies, including a total of 290 patients with cardiogenic pulmonary oedema, were considered. The hospital mortality (relative risk [RR] 0.76, 95% confidence interval [CI] 0.32–1.78; P = 0.52; I(2 )= 0%) and risk for requiring invasive ventilation (RR 0.80, 95% CI 0.33–1.94; P = 0.62; I(2 )= 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. Stratifying studies that used either fixed or titrated pressure during BiPAP treatment and studies involving patients with or without hypercapnia did not change the results. The duration of noninvasive ventilation required until the pulmonary oedema resolved (weighted mean difference [WMD] in hours = 3.65, 95% CI -12.12 to +19.43; P = 0.65, I(2 )= 0%) and length of hospital stay (WMD in days = -0.04, 95% CI -2.57 to +2.48; P = 0.97, I(2 )= 0%) were also not significantly different between the two groups. Based on the limited data available, there was an insignificant trend toward an increase in new onset acute myocardial infarction in patients treated with BiPAP (RR 2.10, 95% CI 0.91–4.84; P = 0.08; I(2 )= 25.3%). CONCLUSION: BiPAP does not offer any significant clinical benefits over CPAP in patients with acute cardiogenic pulmonary oedema. Until a large randomized controlled trial shows significant clinical benefit and cost-effectiveness of BiPAP versus CPAP in patients with acute cardiogenic pulmonary oedema, the choice of modality will depend mainly on the equipment available

Self-directed disability support: building people’s capacity through peer support and action research

How are people with disability experiencing and managing the transition towards self directed support and preparing for the NDIS? In this project, small groups of people with disability around Australia met over 6 months to talk about their disability support. The peer support groups enabled action research about how they are deciding the practical details about support, such as how, when and by whom it is provided

Pericardial Tamponade in a Patient with Inactive Ulcerative Colitis

Cardiac tamponade is a rare extraintestinal manifestation of ulcerative colitis. We present a case report of tamponade occurring four years after curative proctocolectomy and in the absence of any medical therapy for ulcerative colitis. Options for medical management of this condition are also discussed

Clinical Pharmacist-Led Intervention to Improve Statin Metric for Secondary Prevention at Providence Medical Group – Southern Oregon Region

Clinical Pharmacist-Led Intervention to Improve Statin Metric for Secondary Prevention at Providence Medical Group – Southern Oregon Region Chloe Nguyen, PharmD, Judy Wong, PharmD, BCACP, and Karen White, PharmD, BCACP Background: Currently, there is a gap in meeting the statin metric at Providence Medical Group in Southern Oregon Region. The purpose of this project is to identify intervention strategies to improve statin metric for secondary prevention among patients with clinical atherosclerotic cardiovascular disease (ASCVD). Methods: This quality improvement project was approved by the system’s Institutional Review Board. Patients at least 18 years of age with diagnosis of clinical ASCVD not prescribed statin therapy or prescribed sub-optimal statin therapy were included. Different strategies were implemented at Central Point Family Medicine Clinic. A presentation was delivered to the providers in late December to address barriers with statin prescribing. Pre- and post-surveys were collected to assess the effectiveness of the presentation and knowledge of providers regarding statin prescribing in patients with clinical ASCVD. Chart reviews were performed in January on identified patients to provide recommendation to providers. The primary outcomes were to assess impact of academic detailing intervention on perceived barriers on statin initiation or optimization via pre- and post-surveys and to calculate the percentage of approved recommendation from providers. The secondary outcome was the percentage of statins prescribed per each intervention strategy: refer to clinical pharmacist for management, discuss statin therapy during the next appointment with provider, or update problem list and medication list. Results: Prior to the intervention, a majority of providers believed that statins caused myopathy, liver injury, and rhabdomyolysis which can influence their decision when prescribing statin therapies and discussing statin treatment with patients. Post-survey results showed a slight decrease in belief that statins cause myopathy, liver injury, incidental diabetes, cognitive impairment and rhabdomyolysis. In addition, providers were more likely to retry a different statin or at a lower dose if patient had a documented intolerance to previous statin therapy following education. In a sample of 35 chart reviews, 5 patients were receiving sub-optimal statin therapies, 7 had documented reason for statin intolerance, and 3 were not candidates to receive high intensity statin. A majority of recommendations were approved by providers. The most common intervention chosen by providers (51.4%) was to discuss statin options with patient in next office visit. However, no changes were observed from this intervention. Out of the 10 patients who were referred to clinical pharmacy services for management, 5 declined statin and 4 were unable to reach. Only one patient was successfully started on high intensity statin. Conclusions: Beliefs and approaches to statin discussions are varied among PCPs and can be contributing factors for statin initiation or optimization. These results highlight the complexity of finding interventions that would be most successful for improving statin metric for secondary prevention among patients with clinical ASCVD. Nonetheless, we can be vigilant about working with providers to provide recommendations for the remaining patients with clinical ASCVD and create appropriate follow-up plans for those who were unable to be reached and those who do not have upcoming appointment with providers.https://digitalcommons.psjhealth.org/pharmacy_PGY2/1003/thumbnail.jp