Efficacy of afoxolaner against Dermacentor variabilis ticks in dogs

AbstractEfficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Dermacentor variabilis ticks was confirmed in two laboratory studies. Each study utilized a controlled, randomized block design. One day prior to treatment, beagle dogs were infested with 50 unfed adult ticks. Repeat infestations were performed weekly for four weeks. The number of live ticks remaining on each dog was determined 48h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations by D. variabilis ticks and controlled weekly re-infestations with 99.7–100% efficacy up to Day 23 and >97% efficacy at Day 30

Ceramide remodeling and risk of cardiovascular events and mortality

BackgroundRecent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community‐based samples. Methods and ResultsWe developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramides and ratios of these very–long‐chain/long‐chain ceramides in 2642 FHS (Framingham Heart Study) participants and in 3134 SHIP (Study of Health in Pomerania) participants. Over a mean follow‐up of 6 years in FHS, there were 88 CHD and 90 heart failure (HF) events and 239 deaths. Over a median follow‐up time in SHIP of 5.75 years for CHD and HF and 8.24 years for mortality, there were 209 CHD and 146 HF events and 377 deaths. In meta‐analysis of the 2 cohorts and adjusting for standard CHD risk factors, C24:0/C16:0 ceramide ratios were inversely associated with incident CHD (hazard ratio per average SD increment, 0.79; 95% confidence interval, 0.71–0.89; P<0.0001) and inversely associated with incident HF (hazard ratio, 0.78; 95% confidence interval, 0.61–1.00; P=0.046). Moreover, the C24:0/C16:0 and C22:0/C16:0 ceramide ratios were inversely associated with all‐cause mortality (C24:0/C16:0: hazard ratio, 0.60; 95% confidence interval, 0.56–0.65; P<0.0001; C22:0/C16:0: hazard ratio, 0.65; 95% confidence interval, 0.60–0.70; P<0.0001). ConclusionsThe ratio of C24:0/C16:0 ceramides in blood may be a valuable new biomarker of CHD risk, HF risk, and all‐cause mortality in the community

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). Results: Kaplan\u2013Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p &lt; 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02\u20131.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03\u20131.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02\u20131.17, p = 0.01) for overall mortality was observed per 10&nbsp;mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01\u20131.25, p = 0.04) and HR 1.10; 95% CI 1.01\u20131.20, p = 0.02) respectively. HbA1c cut-off values of 39.9&nbsp;mmol/mol (5.8%), 36.6&nbsp;mmol/mol (5.5%), and 38.8&nbsp;mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. Conclusions: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population

Photographic Validation of Target Versus Nontarget Take of Brown Treesnake Baits

Use of toxic baits or other tools for managing nuisance species must ensure that the species of interest is adequately targeted while exposure to nontarget species is minimized. Nontarget takes of acetaminophen‐laced baits for control of invasive brown treesnakes (Boiga irregularis) on Guam may put those animals at risk of lethal intoxication and render the bait unavailable to the intended target species. We used wildlife cameras to identify species removing toxic and nontoxic baits from brown treesnake bait stations designed to exclude nontarget taxa in 2015 and 2016. Throughout various sites and habitat types, and balanced by season (wet vs. dry), we monitored 512 bait stations. From those, 140 of the baits were taken and the species taking the bait was successfully identified. Brown treesnakes took 124 (88.6%) of the baits, 13 (9.3%) were taken by small coconut crabs (Birgus latro), and 3 (2.1%) were taken by monitor lizards (Varanus indicus). The greatest incidence of nontarget bait takes was by small coconut crabs at 2 adjacent sites atop the same cliff line during a single season; 96.9% of bait takes at all other sites were by brown treesnakes. Bait takes by brown treesnakes were particularly infrequent (2.3%) at sites associated with endangered swiftlet (Aerodramus bartschi) caves where intensive snake control was employed. Although the majority of baits in bait stations are taken by brown treesnakes, local and temporal pulses in nontarget species activity, particularly by crabs, may bias results, which would not be accounted for without supplemental validation by cameras

A scintillator‐based approach to monitor secondary neutron production during proton therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135048/1/mp3813.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135048/2/mp3813_am.pd

Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries:23 million person-years of observation

Background:The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods:For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes.</p