Divergence of gastropod life history in contrasting thermal environments in a geothermal lake.

Experiments using natural populations have provided mixed support for thermal adaptation models, probably because the conditions are often confounded with additional environmental factors like seasonality. The contrasting geothermal environments within Lake Mývatn, northern Iceland, provide a unique opportunity to evaluate thermal adaptation models using closely located natural populations. We conducted laboratory common garden and field reciprocal transplant experiments to investigate how thermal origin influences the life history of Radix balthica snails originating from stable cold (6 °C), stable warm (23 °C) thermal environments or from areas with seasonal temperature variation. Supporting thermal optimality models, warm-origin snails survived poorly at 6 °C in the common garden experiment and better than cold-origin and seasonal-origin snails in the warm habitat in the reciprocal transplant experiment. Contrary to thermal adaptation models, growth rate in both experiments was highest in the warm populations irrespective of temperature, indicating cogradient variation. The optimal temperatures for growth and reproduction were similar irrespective of origin, but cold-origin snails always had the lowest performance, and seasonal-origin snails often performed at an intermediate level compared to snails originating in either stable environment. Our results indicate that central life-history traits can differ in their mode of evolution, with survival following the predictions of thermal optimality models, whereas ecological constraints have shaped the evolution of growth rates in local populations.

Quick divergence but slow convergence during ecotype formation in lake and stream stickleback pairs of variable age.

When genetic constraints restrict phenotypic evolution, diversification can be predicted to evolve along so-called lines of least resistance. To address the importance of such constraints and their resolution, studies of parallel phenotypic divergence that differ in their age are valuable. Here, we investigate the parapatric evolution of six lake and stream threespine stickleback systems from Iceland and Switzerland, ranging in age from a few decades to several millennia. Using phenotypic data, we test for parallelism in ecotypic divergence between parapatric lake and stream populations and compare the observed patterns to an ancestral-like marine population. We find strong and consistent phenotypic divergence, both among lake and stream populations and between our freshwater populations and the marine population. Interestingly, ecotypic divergence in low-dimensional phenotype space (i.e. single traits) is rapid and seems to be often completed within 100 years. Yet, the dimensionality of ecotypic divergence was highest in our oldest systems and only there parallel evolution of unrelated ecotypes was strong enough to overwrite phylogenetic contingency. Moreover, the dimensionality of divergence in different systems varies between trait complexes, suggesting different constraints and evolutionary pathways to their resolution among freshwater systems.

Evolution of adaptive diversity and genetic connectivity in Arctic charr (Salvelinus alpinus) in Iceland.

The ecological theory of adaptive radiation predicts that the evolution of phenotypic diversity within species is generated by divergent natural selection arising from different environments and competition between species. Genetic connectivity among populations is likely also to have an important role in both the origin and maintenance of adaptive genetic diversity. Our goal was to evaluate the potential roles of genetic connectivity and natural selection in the maintenance of adaptive phenotypic differences among morphs of Arctic charr, Salvelinus alpinus, in Iceland. At a large spatial scale, we tested the predictive power of geographic structure and phenotypic variation for patterns of neutral genetic variation among populations throughout Iceland. At a smaller scale, we evaluated the genetic differentiation between two morphs in Lake Thingvallavatn relative to historically explicit, coalescent-based null models of the evolutionary history of these lineages. At the large spatial scale, populations are highly differentiated, but weakly structured, both geographically and with respect to patterns of phenotypic variation. At the intralacustrine scale, we observe modest genetic differentiation between two morphs, but this level of differentiation is nonetheless consistent with strong reproductive isolation throughout the Holocene. Rather than a result of the homogenizing effect of gene flow in a system at migration-drift equilibrium, the modest level of genetic differentiation could equally be a result of slow neutral divergence by drift in large populations. We conclude that contemporary and recent patterns of restricted gene flow have been highly conducive to the evolution and maintenance of adaptive genetic variation in Icelandic Arctic charr.

Cognitive decline in high-functioning older adults: reserve or ascertainment bias?

The detection of mild cognitive impairment and dementia in high-functioning older adults can be difficult. It has also been observed that high-functioning persons show a lower prevalence of dementia than low-functioning persons. Three alternative explanations for this observation have been proposed in the literature: brain reserve capacity (BRC), cognitive reserve, and ascertainment bias. With data from a prospective, population-based study of incident dementia, the Canadian Study of Health and Aging (CSHA), we classified participants as being high- (HF) or low-functioning (LF) in three ways: educational and occupational attainment, and estimated premorbid IQ. We observed that fewer HF older adults were diagnosed with dementia after five years, which is in accordance with both the BRC and cognitive reserve models. Contrary to expectations, no difference on rate of memory deterioration was observed between those HF and LF persons who exhibited mild cognitive impairment at CSHA-1. However, HF persons who subsequently were diagnosed with dementia (CSHA-2) showed more rapid decline on five of the six memory measures over time than did LF persons diagnosed with dementia at CSHA-2. When performance on measures of memory functioning at CSHA-1 was examined for highly educated older adults, significantly more of those with dementia at CSHA-2 (n = 59) had scores falling within or below the average range in comparison to normative standards than those who continued to show no cognitive impairment (n = 145). Our findings suggest that the lower incidence of dementia for HF persons may be primarily the result of ascertainment bias, not underlying differences in brain or cognitive reserve.

The Incontinence Impact Questionnaire and the Urogenital Distress Inventory: a revisit of their validity in women without a urodynamic diagnosis.

OBJECTIVES: We sought to assess validity of the Incontinence Impact Questionnaire (IIQ) and the Urogenital Distress Inventory (UDI) (long and short forms) in incontinent women previously urodynamically undiagnosed. STUDY DESIGN: Post hoc analysis of responses to the IIQ and UDI questionnaires were obtained from a trial on a urethral device in community-dwelling incontinent women. Internal consistency and validity were evaluated against the 1-hour pad test. RESULTS: Internal consistency (Cronbach's alpha) for the long forms was high for the IIQ and moderately high for the UDI, good for the IIQ-short, but poor for the UDI-short. Correlations with 1h pad test were low and non-significant for both versions. Correlation of the short with the long forms was high. CONCLUSION: In the community-dwelling population, without a urodynamic diagnosis, neither long nor short versions of the questionnaires correlate with the severity of the urinary incontinence as shown by the pad test. The validity of the current questionnaires in women without urodynamic diagnosis is questionable.

Patient based method of assessing adverse events in clinical trials in rheumatology: the revised Stanford Toxicity Index.

We describe the progress towards developing a patient rated toxicity index that meets all of the patient-important attributes defined by the OMERACT Drug Safety Working Party. These attributes are frequency, severity, importance to patient, importance to the clinician, impact on economics, impact on activities, and integration of adverse effects with benefits. The Stanford Toxicity Index (STI) has been revised to collect all attributes with the exception of impact on activities. However, since the STI is a part of the Health Assessment Questionnaire (HAQ), impact on activities is collected by the HAQ. In particular, a new question asks patients to rate overall satisfaction, taking into consideration both benefits and adverse effects. The next step in the development of this tool is to ensure that the STI meets the OMERACT filter of truth, discrimination, and feasibility. Although truth and feasibility have been confirmed by comparisons within the ARAMIS database, discrimination needs to be assessed in clinical trials.

Development and validation of an indicator of support for community-residing older Canadians.

Lack of social support is an important risk factor for disability, psychiatric illness, cognitive impairment, institutionalization, and mortality. Social networks are also important for the caregiving and emotional support that elderly people need to allow them to function well in the community. This article details the development and validation of an index of the instrumental support available to older community residents in the Canadian Study of Health and Aging (CSHA). Preliminary item review, internal consistency, and exploratory factor analysis were carried out on a random half of the sample. The second half of the sample was used for cross-validation; internal consistency, exploratory factor analysis, and item response theory analysis were carried out. The final scale had six items; alpha internal consistency was 0.76 and IRT reliability was 0.85. A one-factor solution was most easily interpretable. IRT analyses showed that the scale was homogeneous and that most items were highly discriminating. The instrumental support scale also had a high correlation with size of social network; it was related to marital status and gender, and predicted institutionalization between the two phases of the study.

Cognitive impairment, no dementia: concepts and issues.

This article reviews the concept of mild cognitive impairment in groups of people whose cognitive impairment does not warrant a diagnosis of dementia (cognitive impairment, no dementia; CIND). Problems with the application of existing sets of criteria to the Canadian Study of Health and Aging (CSHA) data sets are addressed and a procedure for identifying a subgroup presumed "at risk" for developing dementia is presented. Application of an informant's report of changes in cognitive functioning and neuropsychologists' ratings of mild to severe deficits in any of eight cognitive domains results in approximately half of the CIND cases being identified as "at risk." The rationale for the collection of specific information related to CIND in CSHA-2 is provided. A minority of people identified with CIND at CSHA-2 showed only memory impairment, and most demonstrated cognitive loss over the preceding five-year interval. This article provides a conceptual basis for procedures to identify people with cognitive impairment most likely to decline to dementia.

Data collected in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging collected data focusing on the epidemiology of dementia, using interviews and questionnaires, clinical and neuropsychological examinations, physical measurements and blood collection, and access to public records such as death certificates, from people 65 and over in community (N = 9,008) institutional settings (N = 1,255). The study produced 12 data sets, including community health interviews, clinical and neuropsychological assessments, risk factor questionnaires, and caregiver interviews. This report describes the data collection and processing procedures, summarizes the content of each data set, and outlines the information collected in sufficient detail to permit its suitability for secondary analyses to be scrutinized.

Marital status, dementia and institutional residence among elderly Canadians: the Canadian Study of Health and Aging.

The association between marital status and mortality is well known; marital status has also been related to morbidity. In this paper, we examine the importance of marital status in relation to the presence or absence of dementia and to institutional residence, using data from the Canadian Study of Health and Aging. Three groups are compared: married, single and previously married. We show that the age-standardized prevalence of dementia and the proportions of elderly Canadians living in institutions with and without dementia are highest among single people and are also high for those who were previously married. These associations hold true for both women and men, but the relation between marital status and institutionalization is much stronger for men. Possible explanations and implications for the future care of the elderly are discussed.

Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared.

The objectives of this study were to assess whether Teng's modification of the Mini-Mental State Examination (MMSE) improves its performance as a screening test for cognitive impairment and dementia, and to replicate this comparison in French and English language groups, and for differing assumptions concerning the relative importance of false negative and false positive errors. Screening interviews were conducted with representative samples of people aged 65 or over, set in 36 communities in 10 Canadian provinces. There were 8900 community participants in the Canadian Study of Health and Aging, of whom 1600 also underwent an extensive clinical and neuropsychological examination. Sensitivity, specificity and areas under the receiver operating characteristic (ROC) curve for the original MMSE and modified version (the 3MS) were the main outcome measures. Results are reported for French and English versions of the tests. The results indicate the alpha internal consistency for the 3MS was 0.87, compared to 0.78 for the MMSE. The area under the ROC curve in identifying dementia was 0.93 for the 3MS and 0.89 for the MMSE (p < 0.001). There was less difference between the two tests in identifying all levels of cognitive impairment (AUC 0.80 versus 0.77, p < 0.01). The superiority of the 3MS appears more due to its extended scoring system than to its additional questions. The validity of the MMSE was comparable in English and French samples; results for the 3MS were inconsistent between the two samples, suggesting possible translation problems. In conclusion, the 3MS was superior to the MMSE, justifying the slightly greater burden for its administration and scoring. Neither test worked well in identifying lower levels of cognitive impairment.

Optimal cut-points when screening for more than one disease state: an example from the Canadian Study of Health and Aging.

A method is described for choosing optimal cut-points in screening test with a continuous score in order to divide people into any number of disease categories. The cut-points are chosen to minimize the overall expected loss, given a matrix of losses incurred by misclassifications. It is shown that the optimal cut-points depend on the column differences of the loss matrix. The effect of changing the loss matrix is examined. For the error counting matrix, where misclassifications are given equal weight, it is shown that the relationship between the minimal loss cut-point and the receiver operating characteristic (ROC) curve for two disease categories extends to the general case. The results of a study in which elderly people were screened for cognitive impairment and dementia are used to illustrate the method.

New method to quantify the urodynamic improvement when treating bladder outlet obstruction: the efficacy of transurethral resection in benign prostatic hypertrophy.

A method to measure the urodynamic improvement when treating urethral obstruction is introduced and applied to patients with benign prostatic hypertrophy. The patients performed pressure-flow studies before and 3-6 months after TUR-p. The urethral resistance relation was estimated by curve fitting in the pressure flow plot. The new method quantifies the improvement in urethral resistance as the distance between the urethral resistance relation before and after treatment expressed in pressure units. The distance is measured at the flow rate equal to 75% of the maximum flow rate for the micturition with the lowest maximum flow rate and this distance is called delta-URA. The median improvement after TUR-p was 71 cm H2O (range 2-119). The improvement was strongly correlated to the resistance before treatment and the regression line indicates that the operation normalizes the resistance irrespective of its preoperative value. On the average a lowering of the urethral resistance relation with 8 cm H2O improved the maximum flow rate with 1 ml/s. The greatest advantage with the new method is that it has a high validity and is almost completely insensitive to changes in contractility.