Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Study protocol:the effectiveness and cost effectiveness of a brief behavioural intervention to promote regular self-weighing to prevent weight regain after weight loss: randomised controlled trial (The LIMIT Study)

BACKGROUND: Although obesity causes many adverse health consequences, modest weight loss reduces the incidence. There are effective interventions that help people to lose weight but weight regain is common and long term maintenance remains a critical challenge. As a high proportion of the population of most high and middle income countries are overweight, there are many people who would benefit from weight loss and its maintenance. Therefore, we need to find effective low cost scalable interventions to help people achieve this. One such intervention that has shown promise is regular self-weighing, to check progress against a target, however there is no trial that has tested this using a randomised controlled design (RCT). The aim of this RCT is to evaluate the effectiveness and cost effectiveness of a brief behavioural intervention delivered by non-specialist staff to promote regular self-weighing to prevent weight regain after intentional weight loss. METHODS: A randomised trial of 560 adults who have lost ≥5 % of their initial body weight through a 12 week weight loss programme. The comparator group receive a weight maintenance leaflet, a diagram representing healthy diet composition, and a list of websites for weight control. The intervention group receive the same plus minimally trained telephonists will ask participants to set a weight target and encourage them to weigh themselves daily, and provide support materials such as a weight record card. The primary outcome is the difference between groups in weight change from baseline to 12 months. DISCUSSION: If effective, this study will provide public health agencies with a simple, low cost maintenance intervention that could be implemented immediately. TRIAL REGISTRATION: ISRCTN52341938 Date Registered: 31/03/201

“AI’s gonna have an impact on everything in society, so it has to have an impact on public health”: a fundamental qualitative descriptive study of the implications of artificial intelligence for public health

Background: Our objective was to determine the impacts of artificial intelligence (AI) on public health practice. Methods: We used a fundamental qualitative descriptive study design, enrolling 15 experts in public health and AI from June 2018 until July 2019 who worked in North America and Asia. We conducted in-depth semi-structured interviews, iteratively coded the resulting transcripts, and analyzed the results thematically. Results: We developed 137 codes, from which nine themes emerged. The themes included opportunities such as leveraging big data and improving interventions; barriers to adoption such as confusion regarding AI’s applicability, limited capacity, and poor data quality; and risks such as propagation of bias, exacerbation of inequity, hype, and poor regulation. Conclusions: Experts are cautiously optimistic about AI’s impacts on public health practice, particularly for improving disease surveillance. However, they perceived substantial barriers, such as a lack of available expertise, and risks, including inadequate regulation. Therefore, investment and research into AI for public health practice would likely be beneficial. However, increased access to high-quality data, research and education regarding the limitations of AI, and development of rigorous regulation are necessary to realize these benefits

The Use of Cremation Data for Timely Mortality Surveillance During the COVID-19 Pandemic in Ontario, Canada: Validation Study

Background: Early estimates of excess mortality are crucial for understanding the impact of COVID-19. However, there is a lag of several months in the reporting of vital statistics mortality data for many jurisdictions, including across Canada. In Ontario, a Canadian province, certification by a coroner is required before cremation can occur, creating real-time mortality data that encompasses the majority of deaths within the province. Objective: This study aimed to validate the use of cremation data as a timely surveillance tool for all-cause mortality during a public health emergency in a jurisdiction with delays in vital statistics data. Specifically, this study aimed to validate this surveillance tool by determining the stability, timeliness, and robustness of its real-time estimation of all-cause mortality. Methods: Cremation records from January 2020 until April 2021 were compared to the historical records from 2017 to 2019, grouped according to week, age, sex, and whether COVID-19 was the cause of death. Cremation data were compared to Ontario\u27s provisional vital statistics mortality data released by Statistics Canada. The 2020 and 2021 records were then compared to previous years (2017-2019) to determine whether there was excess mortality within various age groups and whether deaths attributed to COVID-19 accounted for the entirety of the excess mortality. Results: Between 2017 and 2019, cremations were performed for 67.4% (95% CI 67.3%-67.5%) of deaths. The proportion of cremated deaths remained stable throughout 2020, even within age and sex categories. Cremation records are 99% complete within 3 weeks of the date of death, which precedes the compilation of vital statistics data by several months. Consequently, during the first wave (from April to June 2020), cremation records detected a 16.9% increase (95% CI 14.6%-19.3%) in all-cause mortality, a finding that was confirmed several months later with cremation data. Conclusions: The percentage of Ontarians cremated and the completion of cremation data several months before vital statistics did not change meaningfully during the COVID-19 pandemic period, establishing that the pandemic did not significantly alter cremation practices. Cremation data can be used to accurately estimate all-cause mortality in near real-time, particularly when real-time mortality estimates are needed to inform policy decisions for public health measures. The accuracy of this excess mortality estimation was confirmed by comparing it with official vital statistics data. These findings demonstrate the utility of cremation data as a complementary data source for timely mortality information during public health emergencies

Differential Probability Discounting Rates of Gamblers in an American Indian Population

Probability discounting, a subset of behavioral economic research, has a rich history of investigating choice behavior, especially as it pertains to risky decision making. Gambling involves both choice behavior and risky decision making which makes it an ideal behavior to investigate with discounting tasks. With proximity to a casino being one of the biggest risk factors, studies into the American Indian population have been a neglected population of study. Using outcome measures from a pre-scan probability discounting task, the current study equated the scan task to evaluate behavioral and neurobiological differences in gamblers vs. non-gamblers. Gamblers showed differences in behavioral tasks (lower discounting rates) but not in patterns of neural activation

The Grizzly, April 7, 1997

Airband Sets Its New Fundraising Record • Ursinus Students Participate in Model U.N. • Women\u27s Health Discussed in Merck Lecture • Changes for Summer Classes • Letters: Letter of Thanks; Faculty Member Remembered • Opinion: Seminar on Post-Abortion Trauma • Pfahler Observatory Open House for Hale-Bopp Viewing • Something for Everyone in proTheatre Production of The Two Noble Kinsmen • Another Look at the Ursinus Gymnastics Team • The Dangers of Halogen Lamps • Men\u27s Tennis Wins • Courtney Named an All-American • Trecroce Named Player of the Week • Women\u27s Tennis Action • Women\u27s Lacrosse Falls to Middlebury • Softball Drops 3 in a Row • Dickinson Rallies to Take Two From the Bearshttps://digitalcommons.ursinus.edu/grizzlynews/1401/thumbnail.jp

Measuring the quality of life of family carers of people with dementia: development and validation of C-DEMQOL

Purpose We aimed to address gaps identified in the evidence base and instruments available to measure the quality of life (QOL) of family carers of people with dementia, and develop a new brief, reliable, condition-specific instrument. Methods We generated measurable domains and indicators of carer QOL from systematic literature reviews and qualitative interviews with 32 family carers and 9 support staff, and two focus groups with 6 carers and 5 staff. Statements with five tailored response options, presenting variation on the QOL continuum, were piloted (n = 25), pre-tested (n = 122) and field-tested (n = 300) in individual interviews with family carers from North London and Sussex. The best 30 questions formed the C-DEMQOL questionnaire, which was evaluated for usability, face and construct validity, reliability and convergent/discriminant validity using a range of validation measures. Results C-DEMQOL was received positively by the carers. Factor analysis confirmed that C-DEMQOL sum scores are reliable in measuring overall QOL (ω = 0.97) and its five subdomains: ‘meeting personal needs’ (ω = 0.95); ‘carer wellbeing’ (ω = 0.91); ‘carer-patient relationship’ (ω = 0.82); ‘confidence in the future’ (ω = 0.90) and ‘feeling supported’ (ω = 0.85). The overall QOL and domain scores show the expected pattern of convergent and discriminant relationships with established measures of carer mental health, activities and dementia severity and symptoms. Conclusions The robust psychometric properties support the use of C-DEMQOL in evaluation of overall and domain-specific carer QOL; replications in independent samples and studies of responsiveness would be of value

Screening and brief intervention for obesity in primary care:cost-effectiveness analysis in the BWeL trial

This paper is closed access until 31 July 2019.Background: The Brief Intervention for Weight Loss Trial enrolled 1882 consecutively attending primary care patients who were obese and participants were randomised to physicians opportunistically endorsing, offering, and facilitating a referral to a weight loss programme (support) or recommending weight loss (advice). After one year, the support group lost 1.4 kg more (95%CI 0.9 to 2.0): 2.4 kg versus 1.0 kg. We use a cohort simulation to predict effects on disease incidence, quality of life, and healthcare costs over 20 years. Methods: Randomly sampling from the trial population, we created a virtual cohort of 20 million adults and assigned baseline morbidity. We applied the weight loss observed in the trial and assumed weight regain over four years. Using epidemiological data, we assigned the incidence of 12 weight-related diseases depending on baseline disease status, age, gender, body mass index. From a healthcare perspective, we calculated the quality adjusted life years (QALYs) accruing and calculated the incremental difference between trial arms in costs expended in delivering the intervention and healthcare costs accruing. We discounted future costs and benefits at 1.5% over 20 years. Results: Compared with advice, the support intervention reduced the cumulative incidence of weight-related disease by 722/100,000 people, 0.33% of all weight-related disease. The incremental cost of support over advice was £2.01million/100,000. However, the support intervention reduced health service costs by £5.86 million/100,000 leading to a net saving of £3.85 million/100,000. The support intervention produced 992 QALYs/100,000 people relative to advice. Conclusions: A brief intervention in which physicians opportunistically endorse, offer, and facilitate a referral to a behavioural weight management service to patients with a BMI of at least 30 kg/m2 reduces healthcare costs and improves health more than advising weight loss

Developing undergraduate autism education for medical students: a qualitative study

Background Autistic adults and children experience considerable health inequalities and have high rates of premature mortality, hospital admissions and emergency department visits. This is in part due to a lack of autism awareness in the healthcare and social care workforce. A new educational programme, Time for Autism (TfA), for medical students is being developed to address this challenge. This qualitative study was undertaken to support the development of the new programme in order to (1) understand the medical care experiences of parents of autistic children and (2) assess their views on the acceptability of the new TfA programme and willingness to be involved. Methods A convenience sample of 11 parents of autistic children were recruited across the South of England. The ages of the autistic children ranged from 3 to 17 years. Semistructured interviews were completed between October and December 2019. Interview transcripts were analysed using thematic analysis. Results Three key themes were identified: diagnosis, experiences of doctors and TfA considerations. There was support for and willingness to take part in a dedicated autism education programme for medical students, and constructive feedback to inform and improve its delivery. Conclusion The findings from this study provide insights into the medical care experiences of parents/carers of autistic children. Understanding how parents/carers of autistic children would like medical care to be improved can be used to develop TfA and other autism programmes. Parental/carer support for the development of and involvement in an autism medical education programme enhances the feasibility of the new programme

Description of the resolution hierarchy of the global coupled HadGEM3-GC3.1 model as used in CMIP6 HighResMIP experiments

CMIP6 HighResMIP is a new experimental design for global climate model simulations that aims to assess the impact of model horizontal resolution on climate simulation fidelity. We describe a hierarchy of global coupled model resolutions based on the HadGEM3-GC3.1 model that range from an atmosphere-ocean resolution of 130 km-1° to 25 km-1/12°, all using the same forcings and initial conditions. In order to make such high resolution simulations possible, the experiments have a short 30 year spinup, followed by at least century-long simulations with both constant forcing (to assess drift and the focus of this work), and historic forcing. We assess the change in model biases as a function of both atmosphere and ocean resolution, together with the effectiveness and robustness of this new experimental design. We find reductions in the biases in top of atmosphere radiation components and cloud forcing. There are significant reductions in some common surface climate model biases as resolution is increased, particularly in the Atlantic for sea surface temperature and precipitation, primarily driven by increased ocean resolution. There is also a reduction in drift from the initial conditions both at the surface and in the deeper ocean at higher resolution. Using an eddy-present and eddy-rich ocean resolution enhances the strength of the North Atlantic ocean circulation (boundary currents, overturning circulation and heat transports), while an eddy-present ocean resolution has a considerably reduced Antarctic Circumpolar Current strength. All models have a reasonable representation of El Nino – Southern Oscillation. In general the biases present after 30 years of simulations do not change character markedly over longer timescales, justifying the experimental design