Comparison of Size and Geography of Airborne Tungsten Particles in Fallon, Nevada, and Sweet Home, Oregon, with Implications for Public Health

To improve understanding of possible connections between airborne tungsten and public health, size and geography of airborne tungsten particles collected in Fallon, Nevada, and Sweet Home, Oregon, were compared. Both towns have industrial tungsten facilities, but only Fallon has experienced a cluster of childhood leukemia. Fallon and Sweet Home are similar to one another by their particles of airborne tungsten being generally small in size. Meteorologically, much, if not most, of residential Fallon is downwind of its hard metal facility for at least some fraction of time at the annual scale, whereas little of residential Sweet Home is downwind of its tungsten facility. Geographically, most Fallon residents potentially spend time daily within an environment containing elevated levels of airborne tungsten. In contrast, few Sweet Home residents potentially spend time daily within an airborne environment with elevated levels of airborne tungsten. Although it cannot be concluded from environmental data alone that elevated airborne tungsten causes childhood leukemia, the lack of excessive cancer in Sweet Home cannot logically be used to dismiss the possibility of airborne tungsten as a factor in the cluster of childhood leukemia in Fallon. Detailed modeling of all variables affecting airborne loadings of heavy metals would be needed to legitimately compare human exposures to airborne tungsten in Fallon and Sweet Home

Neural Regions Underlying Object and Action Naming: Complementary Evidence from Acute Stroke and Primary Progressive Aphasia

Background: Naming impairment is commonly noted in individuals with aphasia. However, object naming receives more attention than action naming. Furthermore, most studies include participants with aphasia due to only one aetiology, commonly stroke. We developed a new assessment, the Hopkins Action Naming Assessment (HANA), to evaluate action naming impairments. Methods \u3e& Procedures: Participants (N = 138 PPA, N = 37 acute stroke) completed the BNT and HANA. Behavioural performance was compared. A subset of participants (N = 31 PPA, N = 37 acute stroke) provided neuroimaging data. The whole brain was automatically segmented into regions of interest (ROIs). For participants with PPA, the image variables were the ROI volumes, normalised by brain volume. For participants with acute stroke, the image variables were the percentage of each ROI that was lesioned. The relationship between ROIs likely to be involved in naming performance was modelled with LASSO regression. Outcomes & Results: Behavioural results showed a double dissociation in performance: in each group, some participants displayed intact performance relative to healthy controls on actions but not objects and/or significantly better performance on actions than objects, while others showed the opposite pattern. These results support the need to assess both objects and actions when evaluating naming deficits. Neuroimaging results identified different regions associated with object vs. action naming, implicating overlapping but distinct networks of regions. Furthermore, results differed for participants with PPA vs. acute stroke, indicating that critical information may be missed when only one aetiology is considered. Conclusions: Overall, the study provides a more comprehensive picture of the neural bases of naming, underscoring the importance of assessing both objects and actions and considering different aetiologies of damage. It demonstrates the HANA\u27s utility

Neural Correlates of Syntactic Comprehension: A Longitudinal Study

Broca’s area is frequently implicated in sentence comprehension but its specific role is debated. Most lesion studies have investigated deficits at the chronic stage. We aimed (1) to use acute imaging to predict which left hemisphere stroke patients will recover sentence comprehension; and (2) to better understand the role of Broca’s area in sentence comprehension by investigating acute deficits prior to functional reorganization. We assessed comprehension of canonical and noncanonical sentences in 15 patients with left hemisphere stroke at acute and chronic stages. LASSO regression was used to conduct lesion symptom mapping analyses. Patients with more severe word-level comprehension deficits and a greater proportion of damage to supramarginal gyrus and superior longitudinal fasciculus were likely to experience acute deficits prior to functional reorganization. Broca’s area was only implicated in chronic deficits. We propose that when temporoparietal regions are damaged, intact Broca’s area can support syntactic processing after functional reorganization occurs

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A retrospective cohort study of stroke onset: implications for characterizing short term effects from ambient air pollution

<p>Abstract</p> <p>Background</p> <p>Case-crossover studies used to investigate associations between an environmental exposure and an acute health response, such as stroke, will often use the day an individual presents to an emergency department (ED) or is admitted to hospital to infer when the stroke occurred. Similarly, they will use patient's place of residence to assign exposure. The validity of using these two data elements, typically extracted from administrative databases or patient charts, to define the time of stroke onset and to assign exposure are critical in this field of research as air pollutant concentrations are temporally and spatially variable. Our a priori hypotheses were that date of presentation differs from the date of stroke onset for a substantial number of patients, and that assigning exposure to ambient pollution using place of residence introduces an important source of exposure measurement error. The objective of this study was to improve our understanding on how these sources of errors influence risk estimates derived using a case-crossover study design.</p> <p>Methods</p> <p>We sought to collect survey data from stroke patients presenting to hospital EDs in Edmonton, Canada on the date, time, location and nature of activities at onset of stroke symptoms. The daily mean ambient concentrations of NO₂and PM_2.5on the self-reported day of stroke onset was estimated from continuous fixed-site monitoring stations.</p> <p>Results</p> <p>Of the 336 participating patients, 241 were able to recall when their stroke started and 72.6% (95% confidence interval [CI]: 66.9 - 78.3%) experienced stroke onset the same day they presented to the ED. For subjects whose day of stroke onset differed from the day of presentation to the ED, this difference ranged from 1 to 12 days (mean = 1.8; median = 1). In these subjects, there were no systematic differences in assigned pollution levels for either NO₂or PM_2.5when day of presentation rather than day of stroke onset was used. At the time of stroke onset, 89.9% (95% CI: 86.6 - 93.1%) reported that they were inside, while 84.5% (95% CI: 80.6 - 88.4%) reported that for most of the day they were within a 15 minute drive from home. We estimated that due to the mis-specification of the day of stroke onset, the risk of hospitalization for stroke would be understated by 15% and 20%, for NO₂and PM_2.5, respectively.</p> <p>Conclusions</p> <p>Our data suggest that day of presentation and residential location data obtained from administrative records reasonably captures the time and location of stroke onset for most patients. Under these conditions, any associated errors are unlikely to be an important source of bias when estimating air pollution risks in this population.</p

Individual patient data meta-analysis of self-monitoring of blood pressure (BP-SMART): a protocol.

INTRODUCTION: Self-monitoring of blood pressure is effective in reducing blood pressure in hypertension. However previous meta-analyses have shown a considerable amount of heterogeneity between studies, only part of which can be accounted for by meta-regression. This may be due to differences in design, recruited populations, intervention components or results among patient subgroups. To further investigate these differences, an individual patient data (IPD) meta-analysis of self-monitoring of blood pressure will be performed. METHODS AND ANALYSIS: We will identify randomised trials that have compared patients with hypertension who are self-monitoring blood pressure with those who are not and invite trialists to provide IPD including clinic and/or ambulatory systolic and diastolic blood pressure at baseline and all follow-up points where both intervention and control groups were measured. Other data requested will include measurement methodology, length of follow-up, cointerventions, baseline demographic (age, gender) and psychosocial factors (deprivation, quality of life), setting, intensity of self-monitoring, self-monitored blood pressure, comorbidities, lifestyle factors (weight, smoking) and presence or not of antihypertensive treatment. Data on all available patients will be included in order to take an intention-to-treat approach. A two-stage procedure for IPD meta-analysis, stratified by trial and taking into account age, sex, diabetes and baseline systolic BP will be used. Exploratory subgroup analyses will further investigate non-linear relationships between the prespecified variables. Sensitivity analyses will assess the impact of trials which have and have not provided IPD. ETHICS AND DISSEMINATION: This study does not include identifiable data. Results will be disseminated in a peer-reviewed publication and by international conference presentations. CONCLUSIONS: IPD analysis should help the understanding of which self-monitoring interventions for which patient groups are most effective in the control of blood pressure

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies

Comparative phylogeography of reef fishes from the Gulf of Aden to the Arabian Sea reveals two cryptic lineages

Arabian Sea is a heterogeneous region with high coral cover and warm stable conditions at the western end (Djibouti), in contrast to sparse coral cover, cooler temperatures, and upwelling at the eastern end (southern Oman). We tested for barriers to dispersal across this region (including the Gulf of Aden and Gulf of Oman), using mitochondrial DNA surveys of 11 reef fishes. Study species included seven taxa from six families with broad distributions across the Indo-Pacific and four species restricted to the Arabian Sea (and adjacent areas). Nine species showed no significant genetic partitions, indicating connectivity among contrasting environments spread across 2000 km. One butterflyfish (Chaetodon melannotus) and a snapper (Lutjanus kasmira) showed phylogenetic divergences of d = 0.008 and 0.048, respectively, possibly indicating cryptic species within these broadly distributed taxa. These genetic partitions at the western periphery of the Indo-Pacific reflect similar partitions recently discovered at the eastern periphery of the Indo-Pacific (the Hawaiian and the Marquesan Archipelagos), indicating that these disjunctive habitats at the ends of the range may serve as evolutionary incubators for coral reef organisms. © 2017 Springer-Verlag Berlin HeidelbergTh