Chromosome breakpoint distribution of damage induced in peripheral blood lymphocytes by densely ionising radiation

Purpose: To assess the chromosomal breakpoint distribution in human peripheral blood lymphocytes (PBL) after exposure to a low dose of high linear energy transfer (LET) α-particles using the technique of multiplex fluorescence in situ hybridisation (m-FISH). Materials and methods: Separated PBL were exposed in G0 to 0.5 Gy 238 Pu α-particles, stimulated to divide and harvested ~48-50 hours after exposure. Metaphase cells were assayed by m-FISH and chromosome breaks identified. The observed distribution of breaks were then compared with expected distributions of breaks, calculated on the assumption that the distribution of breaks is random with regard to either chromosome volume or chromosome surface area. Results: More breaks than expected were observed on chromosomes 2 and 11, however no particular region of either chromosome was identified as significantly contributing to this over-representation. The identification of hot or cold chromosome regions (pter,p,cen,q,qter) varied depending on whether the data were compared according to chromosome volume or surface area. Conclusions: A deviation from randomness in chromosome breakpoint distribution was observed, and this was greatest when data were compared according to the relative surface area of each individual chromosome (or region). The identification of breaks by m-FISH (i.e. more efficient observation of interchanges than intrachanges) and importance of territorial boundaries on interchange formation are thought to contribute to these differences. The significance of the observed non-random distribution of breaks on chromosomes 2 and 11 in relation to chromatin organisation is unclear

Influence of regional-scale anthropogenic emissions on CO2 distributions over the western North Pacific

We report here airborne measurements of atmospheric CO2 over the western North Pacific during the March-April 2001 Transport and Chemical Evolution over the Pacific (TRACE-P) mission. The CO2 spatial distributions were notably influenced by cyclogenesis-triggered transport of regionally polluted continental air masses. Examination of the CO2 to C2H2/CO ratio indicated rapid outflow of combustion-related emissions in the free troposphere below 8 km. Although the highest CO2 mixing ratios were measured within the Pacific Rim region, enhancements were also observed further east over the open ocean at locations far removed from surface sources. Near the Asian continent, discrete plumes encountered within the planetary boundary layer contained up to 393 ppmv of CO2. Coincident enhancements in the mixing ratios of C2Cl4, C2H2, and C2H4 measured concurrently revealed combustion and industrial sources. To elucidate the source distributions of CO2, an emissions database for Asia was examined in conjunction with the chemistry and 5-day backward trajectories that revealed the WNW/W sector of northeast Asia was a major contributor to these pollution events. Comparisons of NOAA/CMDL and JMA surface data with measurements obtained aloft showed a strong latitudinal gradient that peaked between 35° and 40°N. We estimated a net CO2 flux from the Asian continent of approximately 13.93 Tg C day-1 for late winter/early spring with the majority of the export (79%) occurring in the lower free troposphere (2-8 km). The apportionment of the flux between anthropogenic and biospheric sources was estimated at 6.37 Tg C day-1 and 7.56 Tg C day-1, respectively

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

Introduction: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. Methods: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. Results: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. Conclusions: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation

Labrador retrievers under primary veterinary care in the UK: demography, mortality and disorders

Abstract Background Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care. Methods The VetCompass™ programme collects electronic patient record data on dogs attending UK primary-care veterinary practices. Demographic analysis covered all33,320 Labrador retrievers in the VetCompass™ database under veterinary care during 2013 while disorder and mortality data were extracted from a random sample of 2074 (6.2%) of these dogs. Results Of the Labrador retrievers with information available, 15,427 (46.4%) were female and 15,252 (53.6%) were male. Females were more likely to be neutered than males (59.7% versus 54.8%, P <  0.001). The overall mean adult bodyweight was 33.0 kg (SD 6.1). Adult males were heavier (35.2 kg, SD 5.9 kg) than adult females (30.4 kg, SD 5.2 kg) (P <  0.001). The median longevity of Labrador retrievers overall was 12.0 years (IQR 9.9–13.8, range 0.0–16.0). The most common recorded colours were black (44.6%), yellow (27.8%) and liver/chocolate (reported from hereon as chocolate) (23.8%). The median longevity of non-chocolate coloured dogs (n = 139, 12.1 years, IQR 10.2–13.9, range 0.0–16.0) was longer than for chocolate coloured animals (n = 34, 10.7 years, IQR 9.0–12.4, range 3.8–15.5) (P = 0.028). Of a random sample of 2074 (6.2%) Labrador retrievers under care in 2013 that had full disorder data extracted, 1277 (61.6%) had at least one disorder recorded. The total number of dogs who died at any date during the study was 176. The most prevalent disorders recorded were otitis externa (n = 215, prevalence 10.4%, 95% CI: 9.1–11.8), overweight/obesity (183, 8.8%, 95% CI: 7.6–10.1) and degenerative joint disease (115, 5.5%, 95% CI: 4.6–6.6). Overweight/obesity was not statistically significantly associated with neutering in females (8.3% of entire versus 12.5% of neutered, P = 0.065) but was associated with neutering in males (4.1% of entire versus 11.4% of neutered, P < 0.001). The prevalence of otitis externa in black dogs was 12.8%, in yellow dogs it was 17.0% but, in chocolate dogs, it rose to 23.4% (P < 0.001). Similarly, the prevalence of pyo-traumatic dermatitis in black dogs was 1.1%, in yellow dogs it was 1.6% but in chocolate dogs it rose to 4.0% (P = 0.011). Conclusions The current study assists prioritisation of health issues within Labrador retrievers. The most common disorders were overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier females. These results can alert prospective owners to potential health issues and inform breed-specific wellness checks

Widespread platinum anomaly documented at theYounger Dryas onset in North American sedimentary sequences

Previously, a large platinum (Pt) anomaly was reported in the Greenland ice sheet at the Younger Dryas boundary (YDB) (12,800 Cal B.P.). In order to evaluate its geographic extent, fire-assay and inductively coupled plasma mass spectrometry (FA and ICP-MS) elemental analyses were performed on 11 widely separated archaeological bulk sedimentary sequences. We document discovery of a distinct Pt anomaly spread widely across North America and dating to the Younger Dryas (YD) onset. The apparent synchroneity of this widespread YDB Pt anomaly is consistent with Greenland Ice Sheet Project 2 (GISP2) data that indicated atmospheric input of platinum-rich dust. We expect the Pt anomaly to serve as a widely-distributed time marker horizon (datum) for identification and correlation of the onset of the YD climatic episode at 12,800 Cal B.P. This Pt datum will facilitate the dating and correlating of archaeological, paleontological, and paleoenvironmental data between sequences, especially those with limited age control

Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 μm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m(2) resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 μg/m(3) change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

"Water, Water, Every Where": Nuances for a Water Industry Critical Infrastructure Specification Exemplar

The water infrastructure is critical to human life, but little attention has been paid to the nuances of the water industry. Without such attention, evaluating security innovation in this domain without compromising the productivity goals when delivering water services is difficult. This paper proposes four nuances that need to be incorporated into a representative specification exemplar for the water industry; these provided input to the exemplar based on a fictional water company

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

INTRODUCTION: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. METHODS: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. RESULTS: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. CONCLUSIONS: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation