Vasodilatation in the rat dorsal hindpaw induced by activation of sensory neurons is reduced by Paclitaxel

Peripheral neuropathy is a major side effect following treatment with the cancer chemotherapeutic drug paclitaxel. Whether paclitaxel-induced peripheral neuropathy is secondary to altered function of small diameter sensory neurons remains controversial. To ascertain whether the function of the small diameter sensory neurons was altered following systemic administration of paclitaxel, we injected male Sprague Dawley rats with 1 mg/kg paclitaxel every other day for a total of four doses and examined vasodilatation in the hindpaw at day 14 as an indirect measure of calcitonin gene related peptide (CGRP) release. In paclitaxel-treated rats, the vasodilatation induced by either intradermal injection of capsaicin into the hindpaw or electrical stimulation of the sciatic nerve was significantly attenuated in comparison to vehicle-injected animals. Paclitaxel treatment, however, did not affect direct vasodilatation induced by intradermal injection of methacholine or CGRP, demonstrating that the blood vessels’ ability to dilate was intact. Paclitaxel treatment did not alter the compound action potentials or conduction velocity of C-fibers. The stimulated release of CGRP from the central terminals in the spinal cord was not altered in paclitaxel-injected animals. These results suggest that paclitaxel affects the peripheral endings of sensory neurons to alter transmitter release, and this may contribute to the symptoms seen in neuropathy

Association between Activity Space Exposure to Food Establishments and Individual Risk of Overweight

Objective: Environmental exposure to food sources may underpin area level differences in individual risk for overweight. Place of residence is generally used to assess neighbourhood exposure. Yet, because people are mobile, multiple exposures should be accounted for to assess the relation between food environments and overweight. Unfortunately, mobility data is often missing from health surveys. We hereby test the feasibility of linking travel survey data with food listings to derive food store exposure predictors of overweight among health survey participants. Methods: Food environment exposure measures accounting for non-residential activity places (activity spaces) were computed and modelled in Montreal and Quebec City, Canada, using travel surveys and food store listings. Models were then used to predict activity space food exposures for 5,578 participants of the Canadian Community Health Survey. These food exposure estimates, accounting for daily mobility, were used to model self-reported overweight in a multilevel framework. Median Odd Ratios were used to assess the proportion of between-neighborhood variance explained by such food exposure predictors. Results: Estimates of food environment exposure accounting for both residential and non-residential destinations were significantly and more strongly associated with overweight than residential-only measures of exposure for men. For women, residential exposures were more strongly associated with overweight than non-residential exposures. In Montreal, adjusted models showed men in the highest quartile of exposure to food stores were at lesser risk of being overweight considering exposure to restaurants (OR = 0.36 [0.21–0.62]), fast food outlets (0.48 [0.30–0.79]), or corner stores (0.52 [0.35–0.78]). Conversely, men experiencing the highest proportion of restaurants being fast-food outlets were at higher risk of being overweight (2.07 [1.25–3.42]). Women experiencing higher residential exposures were at lower risk of overweight. Conclusion: Using residential neighbourhood food exposure measures may underestimate true exposure and observed associations. Using mobility data offers potential for deriving activity space exposure estimates in epidemiological models

EFFECT OF FATIGUE ON KINEMATIC AND KINETICS OF YOUTH RUNNERS: A PILOTSTUDY

The purpose of this study was to investigate the vertical ground reaction forces and heel acceleration of young runners and how they change with fatigue. Young distance athletes (n=4) completed a fatiguing run on a treadmill while kinematic and kinetic data were recorded at the beginning, middle, and ends of their runs. Changes in ground reaction forces and limb acceleration were highly runner-specific, but demonstrate the need for a larger-scale study on the effects of fatigue on developing runners

Funding Changes from the Department of Veterans Affairs: Measuring the Impact on Undergraduate Flight Student Career and Academic Goals

Financial support for the education of veterans and their dependents has been a part of higher education since after the Second World War. This support is also essential to assist veterans in their transition from military to civilian careers. Periodically, funding for educational financial support from the VA comes under scrutiny from the public, Congress, and special interest groups. Recent criticism of excessive VA payments for veterans undertaking flight training at public institutions of higher education has resulted in multiple legislative proposals to limit (cap) or eliminate flight training funding. This article focuses on changes to potential student outcomes if either of these changes is implemented. Forty students currently receiving veteran benefits and enrolled in flight or flight-related degree programs at a four-year public institution were surveyed. Thirty-two percent of respondents would change to a non-flying major or leave college if funding was capped at the proposed level of $20,235. By comparison, 67 percent of respondents would change to a different major or drop out of school if funding for flight training was eliminated. The results of this survey have broad implications for the aviation industry. Public institutions offering flight training may be forced to scale back or close their programs. Furthermore, reducing financial support for flight training costs may cause future veterans to avoid undertaking flight training altogether. In the long term, this may have an adverse impact on the already challenged domestic pilot supply. Avenues for further investigation are proposed. Keywords: pilot supply, flight training, Veteran’s Affairs, educational funding, educational outcomes, completion rates

Global Observations from PHOBOS

Particle production in Au+Au collisions has been measured in the PHOBOS experiment at RHIC for a range of collision energies. Three empirical observations have emerged from this dataset which require theoretical examination. First, there is clear evidence of limiting fragmentation. Namely, particle production in central Au+Au collisions, when expressed as $dN/d\eta'$ ($\eta' \equiv \eta-y_{beam}$), becomes energy independent at high energy for a broad region of $\eta'$ around $\eta'=0$. This energy-independent region grows with energy, allowing only a limited region (if any) of longitudinal boost-invariance. Second, there is a striking similarity between particle production in e+e- and Au+Au collisions (scaled by the number of participating nucleon pairs). Both the total number of produced particles and the longitudinal distribution of produced particles are approximately the same in e+e- and in scaled Au+Au. This observation was not predicted and has not been explained. Finally, particle production has been found to scale approximately with the number of participating nucleon pairs for $N_{part}>65$. This scaling occurs both for the total multiplicity and for high \pT particles (3 <\pT< 4.5 GeV/c).Comment: QM2002 plenary talk, 10 pages, 11 figure

Design and Baseline Characteristics of Participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) Trial of Dulaglutide's Cardiovascular Effects

DigitalThe aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.Ciencias Médicas y de la Salu

Operationalising the 20-minute neighbourhood

BACKGROUND: Recent rapid growth in urban areas and the desire to create liveable neighbourhoods has brought about a renewed interest in planning for compact cities, with concepts like the 20-minute neighbourhood (20MN) becoming more popular. A 20MN broadly reflects a neighbourhood that allows residents to meet their daily (non-work) needs within a short, non-motorised, trip from home. The 20MN concept underpins the key planning strategy of Australia’s second largest city, Melbourne, however the 20MN definition has not been operationalised. This study aimed to develop and operationalise a practical definition of the 20MN and apply this to two Australian state capital cities: Melbourne (Victoria) and Adelaide (South Australia). METHODS: Using the metropolitan boundaries for Melbourne and Adelaide, data were sourced for several layers related to five domains: 1) healthy food; 2) recreational resources; 3) community resources; 4) public open space; and 5) public transport. The number of layers and the access measures required for each domain differed. For example, the recreational resources domain only required a sport and fitness centre (gym) within a 1.5-km network path distance, whereas the public open space domain required a public open space within a 400-m distance along a pedestrian network and 8 ha of public open space area within a 1-km radius. Locations that met the access requirements for each of the five domains were defined as 20MNs. RESULTS: In Melbourne 5.5% and in Adelaide 7.6% of the population were considered to reside in a 20MN. Within areas classified as residential, the median number of people per square kilometre with a 20MN in Melbourne was 6429 and the median number of dwellings per square kilometre was 3211. In Adelaide’s 20MNs, both population density (3062) and dwelling density (1440) were lower than in Melbourne. CONCLUSIONS: The challenge of operationalising a practical definition of the 20MN has been addressed by this study and applied to two Australian cities. The approach can be adapted to other contexts as a first step to assessing the presence of existing 20MNs and monitoring further implementation of this concept. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12966-021-01243-3

Overview of retrospective data harmonisation in the MINDMAP project : process and results

publishedVersionPaid Open Acces

Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies

Researchers rely largely on antibodies to measure the abundance, activity, and localization of a protein, information that provides critical insight into both normal and pathological cellular functions. However, antibodies are not always reliable or universally valid for the methods in which they are used; in particular, the reliability of commercial antibodies against RAS is highly variable. Waters et al . rigorously assessed 22 commercially available RAS antibodies for their utility to detect the distinct RAS isoforms in various cell types and for their use in specific analytical methods. Their findings show how reliably one can interpret the data acquired from each reagent

Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail:a post hoc analysis

Abstract Background The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants Methods We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. Results Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028]. Conclusions These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. Clinical Trial Registration: https://www.clinicaltrials.gouv . Unique Identifier NCT01394952)