Association Between Common Infections and Incident Post-Stroke Dementia:A Cohort Study Using the Clinical Practice Research Datalink

PURPOSE: To investigate the association between common infections and post-stroke dementia in a UK population-based cohort. MATERIALS AND METHODS: A total of 60,392 stroke survivors (51.2% male, median age 74.3 years, IQR 63.9-82.4 years) were identified using primary care records from the Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) with no history of dementia. Primary exposure was any GP-recorded infection (lower respiratory tract infection (LRTI), urinary tract infection (UTI) requiring antibiotics, skin and soft tissue infection requiring antibiotics) occurring after stroke. The primary outcome was incident all-cause dementia recorded in primary care records. In sensitivity analyses, we restricted to individuals with linked hospital records and expanded definitions to include ICD-10 coded hospital admissions. We used multivariable Cox regression to investigate the association between common infections and dementia occurring from 3 months to 5 years after stroke. RESULTS: Of 60,392 stroke survivors, 20,969 (34.7%) experienced at least one infection and overall 4512 (7.5%) developed dementia during follow-up. Early dementia (3 months to 1-year post-stroke) risk was increased in those with at least one GP-recorded infection (HR 1.44, 95% CI 1.21-1.71), with stronger associations when hospitalised infections were included (HR 1.84, 95% CI 1.58-2.14). Late dementia (1-5 years) was only associated with hospitalised, but not with GP-recorded, infections. CONCLUSION: There was evidence of an association between common infections and post-stroke dementia, strongest in the 3-12 months following stroke. Better understanding of this relationship could help inform knowledge of pathways to dementia post-stroke and targeting of preventive interventions

The impact of digital start-up founders’ higher education on reaching equity investment milestones

This paper builds on human capital theory to assess the importance of formal education among graduate entrepreneurs. Using a sample of 4.953 digital start-ups the paper evaluates the impact of start-up founding teams’ higher education on the probability of securing equity investment and subsequent exit for investors. The main findings are: (1), teams with a founder that has a technical education are less likely to remain self-financed and are more likely to secure equity investment and to exit, but the impact of technical education declines with higher level degrees, (2) teams with a founder that has doctoral level business education are less likely to remain self-financed and have a higher probability of securing equity investment, while undergraduate and postgraduate business education have no significant effect, and (3) teams with a founder that has an undergraduate general education (arts and humanities) are less likely to remain self-financed and are more likely to secure equity investment and exit while postgraduate and doctoral general education have no significant effect on securing equity investment and exit. The findings enhance our understanding of factors that influence digital start-ups achieving equity milestones by showing the heterogeneous influence of different types of higher education, and therefore human capital, on new ventures achieving equity milestones. The results suggest that researchers and policy-makers should extend their consideration of universities entrepreneurial activity to include the development of human capital

Expansion of Canopy-Forming Willows Over the Twentieth Century on Herschel Island, Yukon Territory, Canada

Canopy-forming shrubs are reported to be increasing at sites around the circumpolar Arctic. Our results indicate expansion in canopy cover and height of willows on Herschel Island located at 70° north on the western Arctic coast of the Yukon Territory. We examined historic photographs, repeated vegetation surveys, and conducted monitoring of long-term plots and found evidence of increases of each of the dominant canopy-forming willow species (Salix richardsonii, Salix glauca and Salix pulchra), during the twentieth century. A simple model of patch initiation indicates that the majority of willow patches for each of these species became established between 1910 and 1960, with stem ages and maximum growth rates indicating that some patches could have established as late as the 1980s. Collectively, these results suggest that willow species are increasing in canopy cover and height on Herschel Island. We did not find evidence that expansion of willow patches is currently limited by herbivory, disease, or growing conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13280-011-0168-y) contains supplementary material, which is available to authorized users

G-quadruplex structures mark human regulatory chromatin

G-quadruplex (G4) structural motifs have been linked to transcription, replication and genome instability and are implicated in cancer and other diseases. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context. Herein we address this through the development of G4 ChIP-seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We find ∼10,000 G4 structures in human chromatin, predominantly in regulatory, nucleosome-depleted regions. G4 structures are enriched in the promoters and 5' UTRs of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as $\textit{MYC}$. Strikingly, $\textit{de novo}$ and enhanced G4 formation are associated with increased transcriptional activity, as shown by HDAC inhibitor-induced chromatin relaxation and observed in immortalized as compared to normal cellular states. Our findings show that regulatory, nucleosome-depleted chromatin and elevated transcription shape the endogenous human G4 DNA landscape.European Molecular Biology Organization (EMBO Long-Term Fellowship), University of Cambridge, Cancer Research UK (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

A lake as a microcosm: reflections on developments in aquatic ecology

In the present study, we aim at relating Forbes' remarkable paper on "The lake as a microcosm", published 125 years ago, to the present status of knowledge in our own research group. Hence, we relate the observations Forbes made to our own microcosm, Lake Krankesjon in southern Sweden, that has been intensively studied by several research groups for more than three decades. Specifically, we focus on the question: Have we made any significant progress or did Forbes and colleagues blaze the trail through the unknown wilderness and we are mainly paving that intellectual road? We conclude that lakes are more isolated than many other biomes, but have, indeed, many extensions, for example, input from the catchment, fishing and fish migration. We also conclude that irrespective of whether lakes should be viewed as microcosms or not, the paper by Forbes has been exceptionally influential and still is, especially since it touches upon almost all aspects of the lake ecosystem, from individual behaviour to food web interactions and environmental issues. Therefore, there is no doubt that even if 125 years have passed, Forbes' paper still is a source of inspiration and deserves to be read. Hence, although aquatic ecology has made considerable progress over the latest century, Forbes might be viewed as one of the major pioneers and visionary scientists of limnology

Weight outcomes audit in 1.3 million adults during their first 3 months' attendance in a commercial weight management programme

Background: Over sixty percent of adults in the UK are now overweight/obese. Weight management on a national scale requires behavioural and lifestyle solutions that are accessible to large numbers of people. Evidence suggests commercial weight management programmes help people manage their weight but there is little research examining those that pay to attend such programmes rather than being referred by primary care. The objective of this analysis was to evaluate the effectiveness of a UK commercial weight management programme in self-referred, fee-paying participants. Methods: Electronic weekly weight records were collated for self-referred, fee-paying participants of Slimming World groups joining between January 2010 and April 2012. This analysis reports weight outcomes in 1,356,105 adult, non-pregnant participants during their first 3 months’ attendance. Data were analysed by regression, ANOVA and for binomial outcomes, chi-squared tests using the R statistical program. Results: Mean (SD) age was 42.3 (13.6) years, height 1.65 m (0.08) and start weight was 88.4 kg (18.8). Mean start BMI was 32.6 kg/m² (6.3 kg/m²) and 5 % of participants were men. Mean weight change of all participants was −3.9 kg (3.6), percent weight change −4.4 (3.8), and BMI change was −1.4 kg/m² (1.3). Mean attendance was 7.8 (4.3) sessions in their first 3 months. For participants attending at least 75 % of possible weekly sessions (n = 478,772), mean BMI change was −2.5 kg/m² (1.3), weight change −6.8 kg (3.7) and percent weight change −7.5 % (3.5). Weight loss was greater in men than women absolutely (−6.5 (5.3) kg vs −3.8 (3.4) kg) and as a percentage (5.7 % (4.4) vs 4.3 % (3.7)), respectively. All comparisons were significant (p < 0.001). Level of attendance and percent weight loss in the first week of attendance together accounted for 55 % of the variability in weight lost during the study period. Conclusions: A large-scale commercial lifestyle-based weight management programme had a significant impact on weight loss outcomes over 3 months. Higher levels of attendance led to levels of weight loss known to be associated with significant clinical benefits, which on this scale may have an impact on public health

Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer