Exit Polling in Canada: An Experiment

Although exit polling has not been used to study Canadian elections before, such polls have methodological features that make them a potentially useful complement to data collected through more conventional designs. This paper reports on an experiment with exit polling in one constituency in the 2003 Ontario provincial election. Using student volunteers, a research team at Wilfrid Laurier University conducted an exit poll in the bellwether constituency of Kitchener Centre to assess the feasibility of mounting this kind of study on a broader scale. The experiment was successful in a number of respects. It produced a sample of 653 voters that broadly reflected the partisan character of the constituency, and which can hence be used to shed light on patterns of vote-switching and voter motivations in that constituency. It also yielded insights about best practices in mounting an exit poll in the Ontario context, as well as about the potential for using wireless communication devices to transmit respondent data from the field. The researchers conclude that exit polling on a limited basis (selected constituencies) is feasible, but the costs and logistics associated with this methodology make a province-wide or country-wide study unsupportable at present

"Hot and sticky" and "cold and damp" pyroclastic eruptions, and their relationship with topography: valley- and lake-filling ignimbrites, Ardnamurchan, NW Scotland

Peer reviewe

Healthcare costs for metastatic castration‑resistant prostate cancer patients treated with abiraterone or enzalutamide

Objective: The aim was to assess the real-world healthcare resource use and direct medical costs for metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide, in whom chemotherapy is not yet indicated (pre-chemotherapy) or who had previously received docetaxel-based chemotherapy (post-chemotherapy), before commencing these medicines. Methods: A retrospective cost analysis of mCRPC patients who commenced abiraterone or enzalutamide between 2012 and 2015 was conducted. Routinely collected datasets from the largest health board in Scotland and the UK, Greater Glasgow and Clyde, were linked. They contained information on patient demographics, diagnosis, outpatient consultations, hospital admissions, treatments (abiraterone and enzalutamide), and supportive medicines. Unit costs were obtained from the Scottish Health Service Costs, Personal Social Services Research Unit, and British National Formulary. Generalised linear model-based regression was used to estimate total mean direct costs, and two-part models were used to estimate separate cost components. All models were adjusted for propensity score and key variables. Sensitivity analysis was conducted to explore the impact of hypothetical patient access scheme discounts. Results: Estimated total mean direct medical costs of treating mCRPC patients were similar, albeit with wide and overlapping confidence intervals. Across both treatments, patients who received abiraterone or enzalutamide in a pre-chemotherapy setting incurred the highest total mean direct medical costs. However, post-chemotherapy patients were associated with higher outpatient clinic visits, inpatient hospital admissions, and supportive medicines. Regarding relative contribution to the total mean direct medical cost, the treatment costs were the main contributor, followed by inpatient admissions, outpatient clinic visits, and supportive medicines. Conclusion: The total mean direct medical costs were similar for abiraterone and enzalutamide patients. The costs were not driven by the choice of treatment regimen, but treatment setting (pre-chemotherapy or post-chemotherapy indications) and related healthcare resource utilisation. Future studies should focus on economic evaluations, such as cost-effectiveness analyses, using real-world data

Effects of fluid and drinking on pneumonia mortality in older adults: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Advice to drink plenty of fluid is common in respiratory infections. We assessed whether low fluid intake (dehydration) altered outcomes in adults with pneumonia. METHODS: We systematically reviewed trials increasing fluid intake and well-adjusted, well-powered observational studies assessing associations between markers of low-intake dehydration (fluid intake, serum osmolality, urea or blood urea nitrogen, urinary output, signs of dehydration) and mortality in adult pneumonia patients (with any type of pneumonia, including community acquired, health-care acquired, aspiration, COVID-19 and mixed types). Medline, Embase, CENTRAL, references of reviews and included studies were searched to 30/10/2020. Studies were assessed for inclusion, risk of bias and data extracted independently in duplicate. We employed random-effects meta-analysis, sensitivity analyses, subgrouping and GRADE assessment. Prospero registration: CRD42020182599. RESULTS: We identified one trial, 20 well-adjusted cohort studies and one case-control study. None suggested that more fluid (hydration) was associated with harm. Ten of 13 well-powered observational studies found statistically significant positive associations in adjusted analyses between dehydration and medium-term mortality. The other three studies found no significant effect. Meta-analysis suggested doubled odds of medium-term mortality in dehydrated (compared to hydrated) pneumonia patients (GRADE moderate-quality evidence, OR 2.3, 95% CI 1.8 to 2.8, 8619 deaths in 128,319 participants). Heterogeneity was explained by a dose effect (greater dehydration increased risk of mortality further), and the effect was consistent across types of pneumonia (including community-acquired, hospital-acquired, aspiration, nursing and health-care associated, and mixed pneumonia), age and setting (community or hospital). The single trial found that educating pneumonia patients to drink ≥1.5 L fluid/d alongside lifestyle advice increased fluid intake and reduced subsequent healthcare use. No studies in COVID-19 pneumonia met the inclusion criteria, but 70% of those hospitalised with COVID-19 have pneumonia. Smaller COVID-19 studies suggested that hydration is as important in COVID-19 pneumonia mortality as in other pneumonias. CONCLUSIONS: We found consistent moderate-quality evidence mainly from observational studies that improving hydration reduces the risk of medium-term mortality in all types of pneumonia. It is remarkable that while many studies included dehydration as a potential confounder, and major pneumonia risk scores include measures of hydration, optimal fluid volume and the effect of supporting hydration have not been assessed in randomised controlled trials of people with pneumonia. Such trials, are needed as potential benefits may be large, rapid and implemented at low cost. Supporting hydration and reversing dehydration has the potential to have rapid positive impacts on pneumonia outcomes, and perhaps also COVID-19 pneumonia outcomes, in older adults

Salmonella infection in grey seals (Halichoerus grypus), a marine mammal sentinel species:Pathogenicity and molecular typing of Salmonella strains compared with human and livestock isolates

Microbial pollution of the marine environment through land–sea transfer of human and livestock pathogens is of concern.Salmonellawas isolated from rectal swabs of free-ranging and stranded grey seal pups (21.1%; 37/175) and compared with strains from the same serovars isolated from human clinical cases, livestock, wild mammals and birds in Scotland, UK to characterize possible transmission routes using pulsed-field gel electrophoresis and multi-locus variable number of tandem repeat analyses. A higher prevalence ofSalmonellawas found in pups exposed to seawater, suggesting that this may represent a source of this pathogen.SalmonellaBovismorbificans was the most common isolate (18.3% pups; 32/175) and was indistinguishable from isolates found in Scottish cattle.Salmonella Typhimurium was infrequent (2.3% pups; 4/175), mostly similar to isolates found in garden birds and, in one case, identical to a highly multidrug resistant strain isolated from a human child.Salmonella Haifa was rare (1.1% pups; 2/175), but isolates were indistinguishable from that of a human clinical isolate. These results suggest thatS.Bovismorbificans may circulate between grey seal and cattle populations and that bothS.Typhimurium andS.Haifa isolates are shared with humans, raising concerns of microbial marine pollution

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Relationship between the Mediterranean dietary pattern and musculoskeletal health in children, adolescents, and adults: systematic review and evidence map

Context: An understanding of the modifiable effects of diet on bone and skeletal muscle mass and strength over the life course will help inform strategies to reduce age-related fracture risk. The Mediterranean diet is rich in nutrients that may be important for optimal musculoskeletal health. Objective: The aim of this systematic review was to investigate the relationship between a Mediterranean diet and musculoskeletal outcomes (fracture, bone density, osteoporosis, sarcopenia) in any age group. Data Sources: Ten electronic databases were searched. Study Selection: Randomized controlled trials and prospective cohort studies that investigated a traditional Mediterranean diet, published in any language, were eligible. Studies using other designs or other definitions of the Mediterranean diet were collated separately in an evidence map. Data Extraction: Details on study design, methods, population, dietary intervention or exposure, length of follow-up, and effect on or association with musculoskeletal outcomes were extracted. Results: The search yielded 1738 references. Data from eligible randomized controlled trials (n = 0) and prospective cohort studies (n = 3) were synthesized narratively by outcome for the systematic review. Two of these studies reported on hip fracture incidence, but results were contradictory. A third study found no association between the Mediterranean diet and sarcopenia incidence. Conclusions: Overall, the systematic review and evidence map demonstrate a lack of research to understand the relationship between the Mediterranean diet and musculoskeletal health in all ages. Systematic Review Registration: PROSPERO registration number IDCRD42016037038

Is there a common water-activity limit for the three domains of life?

Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a w) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a w. Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a w). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 a w for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a w for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes