Does Place of Residence or Time of Year Affect the Risk of Stroke Hospitalization and Death? A Descriptive Spatial and Temporal Epidemiologic Study

Background

Identifying geographic areas with significantly high risks of stroke is important for informing public health prevention and control efforts. The objective of this study was to investigate geographic and temporal patterns of stroke hospitalization and mortality risks so as to identify areas and seasons with significantly high burden of the disease in Florida. The information obtained will be useful for resource allocation for disease prevention and control.

Methods

Stroke hospitalization and mortality data from 1992 to 2012 were obtained from the Florida Agency for Health Care Administration. Age-adjusted stroke hospitalization and mortality risks for time periods 1992–94, 1995–97, 1998–2000, 2001–03, 2004–06, 2007–09 and 2010–12 were computed at the county spatial scale. Global Moran’s I statistics were computed for each of the time periods to test for evidence of global spatial clustering. Local Moran indicators of spatial association (LISA) were also computed to identify local areas with significantly high risks.

Results

There were approximately 1.5 million stroke hospitalizations and over 196,000 stroke deaths during the study period. Based on global Moran’s I tests, there was evidence of significant (p<0.05) global spatial clustering of stroke mortality risks but no evidence (p>0.05) of significant global clustering of stroke hospitalization risks. However, LISA showed evidence of local spatial clusters of both hospitalization and mortality risks with significantly high risks being observed in the north while the south had significantly low risks of stroke deaths. There were decreasing temporal trends and seasonal patterns of both hospitalization and mortality risks with peaks in the winter.

Conclusions

Although stroke hospitalization and mortality risks have declined in the past two decades, disparities continue to exist across Florida and it is evident from the results of this study that north Florida may, in fact, be part of the stroke belt despite not being in any of the traditional stroke belt states. These findings are useful for guiding public health efforts to reduce/eliminate inequities in stroke outcomes and inform policy decisions. There is need to continually identify populations with significantly high risks of stroke to better guide the targeting of limited resources to the highest risk populations.     

Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model

Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T₂-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases.     

Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients’ feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon.     

Extrafloral nectar increases seed removal by ants in Turnera ulmifolia

To investigate whether extrafloral nectar (EFN) increases seed dispersal in Turnera ulmifolia, we measured seed removal on plants with and without EFN. Plants producing EFN had more seeds removed than control plants, suggesting that EFN does play a role in seed dispersal. This is a novel function of EFN.     

Season,but not experimental warming,affects the activity and temperature sensitivity of extracellular enzymes

Climate change may affect the microbial production and temperature sensitivity of extracellular enzymes that release carbon (C) and nutrients from soil organic matter. We measured the response of six hydrolytic enzymes involved in C, nitrogen (N), and phosphorus (P) degradation to experimental warming in a mixed-deciduous forest persisting on highly-weathered Ultisols (Whitehall Forest, Georgia, US). We found that warming produced no consistent enzyme response. However, we observed significant seasonal variation in enzyme activities, temperature sensitivities and elemental enzyme ratios (C:N and C:P). Seasonal differences in enzyme activity and temperature sensitivity were best explained by soil moisture and temperature. Our results suggest that seasonal dynamics in soil microclimate, organic matter supply, and microbial demand exert more control on enzyme dynamics than does a uniform increase in soil temperature.     

Acoustic sequences in non‐human animals: a tutorial review and prospectus

Animal acoustic communication often takes the form of complex sequences, made up of multiple distinct acoustic units. Apart from the well‐known example of birdsong, other animals such as insects, amphibians, and mammals (including bats, rodents, primates, and cetaceans) also generate complex acoustic sequences. Occasionally, such as with birdsong, the adaptive role of these sequences seems clear (e.g. mate attraction and territorial defence). More often however, researchers have only begun to characterise – let alone understand – the significance and meaning of acoustic sequences. Hypotheses abound, but there is little agreement as to how sequences should be defined and analysed. Our review aims to outline suitable methods for testing these hypotheses, and to describe the major limitations to our current and near‐future knowledge on questions of acoustic sequences. This review and prospectus is the result of a collaborative effort between 43 scientists from the fields of animal behaviour, ecology and evolution, signal processing, machine learning, quantitative linguistics, and information theory, who gathered for a 2013 workshop entitled, ‘Analysing vocal sequences in animals’. Our goal is to present not just a review of the state of the art, but to propose a methodological framework that summarises what we suggest are the best practices for research in this field, across taxa and across disciplines. We also provide a tutorial‐style introduction to some of the most promising algorithmic approaches for analysing sequences. We divide our review into three sections: identifying the distinct units of an acoustic sequence, describing the different ways that information can be contained within a sequence, and analysing the structure of that sequence. Each of these sections is further subdivided to address the key questions and approaches in that area. We propose a uniform, systematic, and comprehensive approach to studying sequences, with the goal of clarifying research terms used in different fields, and facilitating collaboration and comparative studies. Allowing greater interdisciplinary collaboration will facilitate the investigation of many important questions in the evolution of communication and sociality.