A comparison of short-term and long-term air pollution exposure associations with mortality in two cohorts in Scotland

Air pollution–mortality risk estimates are generally larger at longer-term, compared with short-term, exposure time scales. We compared associations between short-term exposure to black smoke (BS) and mortality with long-term exposure–mortality associations in cohort participants and with short-term exposure–mortality associations in the general population from which the cohorts were selected. We assessed short-to-medium–term exposure–mortality associations in the Renfrew–Paisley and Collaborative cohorts (using nested case–control data sets), and compared them with long-term exposure–mortality associations (using a multilevel spatiotemporal exposure model and survival analyses) and short-to-medium–term exposure–mortality associations in the general population (using time-series analyses). For the Renfrew–Paisley cohort (15,331 participants), BS exposure–mortality associations were observed in nested case–control analyses that accounted for spatial variations in pollution exposure and individual-level risk factors. These cohort-based associations were consistently greater than associations estimated in time-series analyses using a single monitoring site to represent general population exposure {e.g., 1.8% [95% confidence interval (CI): 0.1, 3.4%] vs. 0.2% (95% CI: 0.0, 0.4%) increases in mortality associated with 10-μg/m3 increases in 3-day lag BS, respectively}. Exposure–mortality associations were of larger magnitude for longer exposure periods [e.g., 3.4% (95% CI: –0.7, 7.7%) and 0.9% (95% CI: 0.3, 1.5%) increases in all-cause mortality associated with 10-μg/m3 increases in 31-day BS in case–control and time-series analyses, respectively; and 10% (95% CI: 4, 17%) increase in all-cause mortality associated with a 10-μg/m3 increase in geometic mean BS for 1970–1979, in survival analysis]. After adjusting for individual-level exposure and potential confounders, short-term exposure–mortality associations in cohort participants were of greater magnitude than in comparable general population time-series study analyses. However, short-term exposure–mortality associations were substantially lower than equivalent long-term associations, which is consistent with the possibility of larger, more persistent cumulative effects from long-term exposures

Epidemiology of occupational hypersensitivity pneumonitis; reports from the SWORD scheme in the UK from 1996 to 2015

Objective To estimate the reported incidence of occupational hypersensitivity pneumonitis (OHP) in the UK and to consider whether the pattern of attributed causation has changed over time. Methods All cases of OHP reported to the SWORD scheme between January 1996 and December 2015 were classified into 1 of 10 categories of the suspected agent. Cases were grouped into four 5-year time periods to examine any changing pattern in incidence or suspected causation. For each time period, the annual incidence was calculated using the estimated number of reported cases and the working population of the UK. Results Between 1996 and 2015, there were 202 actual cases of OHP reported to SWORD, equating to an estimated 818 cases, when adjusting for the sampling ratio. Over this period, the annual UK incidence was 1.4 per million workers. The mean (SD) age of reported cases was 52 (13) years, and cases were four-times more likely to be men than women. Over the study period, there was a fall in the proportion of cases reported to be due to agricultural exposures (44–12%), and an increase in cases due to metalworking fluids (MWFs, 2–45%). Conclusions Over the last 20 years, the incidence of OHP in the UK has been ∼1–2 cases per million workers per year. Working with water-based MWFs is now the most commonly suspected causative exposure for OHP cases reported to the SWORD scheme in the UK

Immunohistochemical detection of ERβ in breast cancer: towards more detailed receptor profiling?

Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERβ has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemical detection of ERβ in archival breast tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Estimation of Excess Mortality Rates Among US Assisted Living Residents During the COVID-19 Pandemic.

The devastating effects of COVID-19 among older adults residing in long-term care settings have been well documented.1 Although much attention has been paid to COVID-19–associated mortality in nursing homes,2 less is understood about its effects on assisted living residents. Most assisted living residents are aged 80 years or older and many have multiple chronic illnesses, making them highly susceptible to poor outcomes of COVID-19.3 This study examines the excess mortality among a US cohort of assisted living residents during the COVID-19 pandemic

Accessing Opportunities for Household Provisioning Post-COVID-19

In this project, we used a mixed-methods study to collect critical information to evaluate the extent to which people modified their shopping behavior, either by choice or necessity, to meet their provisioning needs during the COVID-19 crisis and the following recovery. First, four waves of a cross-sectional survey were administered online to a representative sample of households in Arizona, Florida, Michigan, Oregon, and Washington. This longitudinal, comparative study responded directly to a critical research gap and advanced behavioral science by providing a rich survey dataset to support and test theories of behavioral change and technology adoption. Second, focus groups were conducted with older adults in Oregon to discuss their arc of technology adoption for grocery shopping. Focus groups were also conducted with two sets of mentors who provide assistance to family members and friends with online food purchases to understand what kinds of interventions might be necessary to broaden access to e-commerce and delivery platforms for vulnerable populations. This report presents high-level descriptive statistics from these surveys comparing results by wave and/or by state. The findings from the focus groups with older adults and mentors are also described. The findings of this research are critical for emergency planning but also for understanding the ever-changing mechanism used to access retail and service opportunities (whether in-person vs. online), and the opportunities for future interventions to remedy barriers to accessing food that are relevant after the pandemic recovery

SD-208, a novel protein kinase D inhibitor, blocks prostate cancer cell proliferation and tumor Growth in Vivo by inducing G2/M cell cycle arrest

Protein kinase D (PKD) has been implicated in many aspects of tumorigenesis and progression, and is an emerging molecular target for the development of anticancer therapy. Despite recent advancement in the development of potent and selective PKD small molecule inhibitors, the availability of in vivo active PKD inhibitors remains sparse. In this study, we describe the discovery of a novel PKD small molecule inhibitor, SD-208, from a targeted kinase inhibitor library screen, and the synthesis of a series of analogs to probe the structure-activity relationship (SAR) vs. PKD1. SD-208 displayed a narrow SAR profile, was an ATP-competitive pan-PKD inhibitor with low nanomolar potency and was cell active. Targeted inhibition of PKD by SD-208 resulted in potent inhibition of cell proliferation, an effect that could be reversed by overexpressed PKD1 or PKD3. SD-208 also blocked prostate cancer cell survival and invasion, and arrested cells in the G2/M phase of the cell cycle. Mechanistically, SD-208-induced G2/M arrest was accompanied by an increase in levels of p21 in DU145 and PC3 cells as well as elevated phosphorylation of Cdc2 and Cdc25C in DU145 cells. Most importantly, SD-208 given orally for 24 days significantly abrogated the growth of PC3 subcutaneous tumor xenografts in nude mice, which was accompanied by reduced proliferation and increased apoptosis and decreased expression of PKD biomarkers including survivin and Bcl-xL. Our study has identified SD-208 as a novel efficacious PKD small molecule inhibitor, demonstrating the therapeutic potential of targeted inhibition of PKD for prostate cancer treatment

Association Between State Regulations Supportive of Third-party Services and Likelihood of Assisted Living Residents in the US Dying in Place

Importance Older adults are increasingly residing in assisted living residences during their last year of life. The regulations guiding these residential care settings differ between and within the states in the US, resulting in diverse policies that may support residents who wish to die in place. Objective To examine the association between state regulations and the likelihood of assisted living residents dying in place. The study hypothesis was that regulations supporting third-party services, such as hospice, increase the likelihood of assisted living residents dying in place. Design, Setting, and Participants This retrospective cohort study combined data about assisted living residences in the US from state registries with an inventory of state regulations and administrative claims data. The study participants comprised 168 526 decedents who were Medicare beneficiaries, resided in 8315 large, assisted living residences (with ≥25 beds) across 301 hospital referral regions during the last 12 months of their lives, and died between 2017 and 2019. Descriptive analyses were performed at the state level, and 3-level multilevel models were estimated to examine the association between supportive third-party regulations and dying in place in assisted living residences. The data were analyzed from September 2021 to August 2022. Exposures Supportive (vs “silent,” ie, not explicitly mentioned in regulatory texts) state regulations regarding hospice care, private care aides, and home health services, as applicable to licensed/registered assisted living residences across the US. Main Outcomes and Measures Presence in assisted living residences on the date of death. Results The median (IQR) age of the 168 526 decedents included in the study was 90 (84-94) years. Of these, 110 143 (65.4%) were female and 158 491 (94.0%) were non-Hispanic White. Substantial variation in the percentage of assisted living residents dying in place was evident across states, from 18.0% (New York) to 73.7% (Utah). Supportive hospice and home health regulations were associated with a higher odds of residents dying in place (adjusted odds ratio [AOR], 1.38; 95% CI, 1.24-1.54; P \u3c .001; and AOR, 1.21; 95% CI, 1.10-1.34; P \u3c .001, respectively). In addition, hospice regulations remained significant in fully adjusted models (AOR, 1.46; 95% CI, 1.25-1.71). Conclusions and Relevance The findings of this cohort study suggest that a higher percentage of assisted living residents died in place in US states with regulations supportive of third-party services. In addition, assisted living residents in licensed settings with regulations supportive of hospice regulations were especially likely to die in place