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Is antioxidant use protective of cognitive function in the community-dwelling elderly?

BACKGROUND: The role of oxidative stress in the pathogenesis of diseases such as macular degeneration, certain types of cancer, and Alzheimer's disease has received much attention. Thus, there is considerable interest in the potential contribution of antioxidants to the prevention of these diseases. OBJECTIVE: The objective of this study was to determine whether use of supplemental antioxidants (vitamins A, C, or E, plus selenium or zinc) was associated with a reduced risk of development of cognitive impairment or cognitive decline in a representative sample of the community-dwelling elderly. METHODS: The sample consisted of 2082 nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly who were not cognitively impaired at the 1989-1990 interview (baseline for the present analysis). Medication use was determined during in-home interviews. Cognitive function was assessed 3 and 7 years from baseline in terms of incident cognitive impairment, as measured on the Short Portable Mental Status Questionnaire (SPMSQ) using specific cut points (number of errors) based on race and education, and cognitive decline, defined as an increase of > or = 2 errors on the SPMSQ. Multivariate analyses were performed using weighted data adjusted for sampling design and controlled for sociodemographic characteristics, health-related behaviors, and health status. RESULTS: At baseline, 224 (10.8%) subjects were currently taking a supplement containing an antioxidant. During the follow-up period, 24.0% of subjects developed cognitive impairment and 34.5% experienced cognitive decline. Current antioxidant users had a 34.0% lower risk of developing cognitive impairment compared with non-antioxidant users (adjusted relative risk [RR], 0.66; 95% CI, 0.44-1.00) and a 29.0% lower risk of experiencing cognitive decline (adjusted RR, 0.71; 95% CI, 0.49-1.01). CONCLUSION: The results of this analysis suggest a possible beneficial effect of antioxidant use in terms of reducing cognitive decline among the community-dwelling elderly.

Age Factors↗

Mitochondrial DNA diversity in nematodes.

The relatively small literature on mitochondrial DNA (mtDNA) diversity in nematode species is summarized here. Nematodes show a wide range of overall genetic diversities and population genetic structures. Species-wide levels of diversity correlate strongly with the breeding system and other life cycle features that control effective population size. Obligate outcrossers that parasitize mobile vertebrate hosts are the most diverse, species having hermaphroditic stages are less so, and species having asexual reproductive stages appear even less diverse. Nevertheless, these conclusions are preliminary because there exist so few data on DNA diversity in nematodes. What is needed are more comparative studies using similar sampling designs and the same DNA markers, including nuclear loci and further work with mtDNA.

Animals↗

Prevalence, service use, and demographic correlates of 12-month DSM-IV psychiatric disorders in Mexico: results from the Mexican National Comorbidity Survey.

BACKGROUND: This paper describes the 12-month prevalence, severity and demographic correlates of 16 DSM-IV psychiatric disorders and service utilization in the Mexican urban population aged 18-65 years of age. This is representative of 75% of the national adult population. METHOD: The sample design was a strict probability selection scheme. The response rate was 76.6%. The World Mental Health Survey version of the Composite International Diagnostic Interview was installed on laptops and administered by lay interviewers. An international WHO task force carried out its translation into Spanish. RESULTS: The 12-month prevalence of any disorder was 12.1%. The most common disorders were specific phobia (4.0%), major depressive disorder (3.7%) and alcohol abuse or dependence (2.2%). The 12-month prevalence of very severe disorders was 3.7% of which only 24% used any services. Age was the only variable associated with any 12-month disorder, with the younger more likely to report any disorder. Income was associated with severity, with low and low-average incomes more likely to report a 12-month disorder. Females were more likely to report a mood and anxiety disorder, but less likely to report a substance disorder. The group of separated/widowed/divorced was more likely to report a mood and an impulse-control disorder. CONCLUSIONS: The results show that while psychiatric disorders are common in the Mexican population, very severe mental disorders are less common and there is extreme under-utilization of mental health services.

Adolescent↗

The Personal Health Questionnaire: a new screening instrument for detection of ICD-10 depressive disorders in primary care.

BACKGROUND: The next generation of studies on antidepressant drug prescriptions in general practice needs to assess both the patterns of prescription and its appropriateness. This study aimed to assess the performance of the Personal Health Questionnaire (PHQ), a new questionnaire for detecting individuals with ICD- 10 depressive disorders, to be used in association with companion instruments for assessing the 'quality' of antidepressant prescriptions in primary care settings. METHODS: The PHQ was completed by 1,413 primary care attenders (100 were re-tested after 7-14 days) and 139 were selected and interviewed using the SCAN-2 and the 17-item HDRS. All data were analysed using appropriately weighted procedures to control for two-phase sampling design and non-response bias. Individual weights were estimated by logistic regression analysis and trimming strategy. RESULTS: PHQ internal consistency and test-retest on both Likert score and number of symptoms were high. The PHQ discriminated well between individuals with and without depressive disorders. A Likert score > or = 9 provided a good trade-off between sensitivity (0.78) and specificity (0.83). The screening accuracy of the PHQ in detecting subjects likely to benefit from antidepressant drug treatment (SCAN cases with a HDRS total score of 13 or higher) was satisfactory (ROC area 0.87: sensitivity 0.84; specificity 0.78). CONCLUSIONS: The PHQ can be strongly suggested as an accurate and economic screener to identify primary care attenders at high risk of being clinically depressed. However, in order to identify patients requiring antidepressant drug treatment, a second-phase assessment of PHQ high scorers (total score of > or = 10), using the HDRS, is needed.

Adult↗

Determination of the total oxygen isotopic composition of nitrate and the calibration of a delta 17O nitrate reference material.

A thermal decomposition method was developed and tested for the simultaneous determination of delta 18O and delta 17O in nitrate. The thermal decomposition of AgNO3 allows for the rapid and accurate determination of 18O/ 16O and 17O/16O isotopic ratios with a precision of +/- 1.5 per thousand for delta 18O and +/- 0.11 per thousand for delta 17O (delta 17O = delta 17O - 0.52 x delta 18O). The international nitrate isotope reference material IAEA-NO3 yielded a delta 18O value of +23.6 per thousand and delta 17O of -0.2 per thousand, consistent with normal terrestrial mass-dependent isotopic ratios. In contrast, a large sample of NaNO3 from the Atacama Desert, Chile, was found to have delta 17O = 21.56 +/- 0.11 per thousand and delta 18O = 54.9 +/- 1.5 per thousand, demonstrating a substantial mass-independent isotopic composition consistent with the proposed atmospheric origin of the desert nitrate. It is suggested that this sample (designated USGS-35) can be used to generate other gases (CO2, CO, N2O, O2) with the same delta 17O to serve as measurement references for a variety of applications involving mass-independent isotopic compositions in environmental studies.

Journal Article↗

Dynamic isoelectric focusing for proteomics.

Dynamic isoelectric focusing is a new technique that is related to capillary isoelectric focusing but uses additional high-voltage power supplies to provide control over the shape of the electric field within the capillary. Manipulation of the electric field changes the pH gradient, enabling both the location and width of the focused protein bands to be controlled. The proteins can be migrated to a designated sampling point while remaining focused, where they can be collected for further analysis. This ability to collect and isolate the protein bands while maintaining a high peak capacity demonstrates that dynamic isoelectric focusing has great potential as a first dimension in a multidimensional separation system. Dynamic isoelectric focusing can achieve a peak capacity of over 1000, as shown by both mass spectrometry analysis and direct imaging.

Animals↗

Results of a new classification algorithm combining K nearest neighbors and recursive partitioning.

We present results of a new computational learning algorithm combining favorable elements of two well-known techniques: K nearest neighbors and recursive partitioning. Like K nearest neighbors, the method provides an independent prediction for each test sample under consideration, while like recursive partitioning, it incorporates an automatic selection of important input variables for model construction. The new method is applied to the problem of correctly classifying a set of chemical data samples designated as being either active or inactive in a biological screen. Training is performed at varying levels of intrinsic model complexity, and classification performance is compared to that of both K nearest neighbor and recursive partitioning models trained using the identical protocol. We find that the cross-validated performance of the new method outperforms both of these standard techniques over a considerable range of user parameters. We discuss advantages and drawbacks of the new method, with particular emphasis on its parameter robustness, required training time, and performance with respect to chemical structural class.

Journal Article↗

Sequencing of specific copolymer oligomers by electron-capture-dissociation mass spectrometry.

Although a poly(ethylene/propylene glycol) (PEG/PPG) copolymer mixture is far too complex (approximately 150 oligomeric formulas) for conventional purification, oligomer ion compositions of <1% abundance can be separated by Fourier transform mass spectrometry and dissociated into sequence-specific fragment ions. Using collisionally activated dissociation (CAD) or other conventional energetic methods, we found that misleading rearrangements are common; however, these are negligible with electron capture dissociation (ECD), consistent with its nonergodic mechanism. Despite the lack of reference compounds, ECD of five oligomers ranging from PEG(1)PPG(18) to PEG(9)PPG(15) shows that approximately 80% of their isomers have all PEG units at one end, while CAD gave lower values because of an approximately 21% rearrangement loss of internal monomer units. In contrast to the indicated triblock "PEG/PPG/PEG" sample designation of this commercial surfactant, all of these oligomers are found to consist primarily of diblock PEG/PPG structures, so that their termini differ significantly in hydrophobicity, as expected for a surfactant.

Glycols↗

alpha-tocopherol content of Greek virgin olive oils.

alpha-Tocopherol, the main tocopherol homologue found in olive oil, was determined using normal phase HPLC. Ninety Greek virgin olive oils, selected according to a designed sampling protocol from different cultivars and regions all over Greece for three successive crop years, were analyzed. For a specific olive cultivar, which is widely used for the production of olive oil in Greece, additional measurements were made to study the effect of milling conditions on alpha-tocopherol concentration. Finally, a significant number of commercial olive oil samples (25) obtained from the retail market were analyzed. High concentrations of alpha-tocopherol were observed in most of the samples selected from various regions. Values ranging between 98 and 370 mg/kg were found (>200 mg/kg in 60% of samples). Extraction conditions were not found to influence alpha-tocopherol level. alpha-Tocopherol content of retail market samples was high, ranging from 120 to 250 mg/kg of oil (>180 mg/kg in 60% of samples). Storage of samples under domestic conditions for two years showed that good handling is quite important for retaining high alpha-tocopherol levels and for increasing, thus, the storage life and nutritional value of this exquisite oil.

Chromatography, High Pressure Liquid↗

For what applications can probability and non-probability sampling be used?

Almost any type of sample has some utility when estimating population quantities. The focus in this paper is to indicate what type or combination of types of sampling can be used in various situations ranging from a sample designed to establish cause-effect or legal challenge to one involving a simple subjective judgment. Several of these methods have little or no utility in the scientific area but even in the best of circumstances, particularly complex ones, both probabilistic and non-probabilistic procedures have to be used because of lack of knowledge and cost. We illustrate this with a marbled murrelet example.

Ecosystem↗

Evaluating pharmacokinetic/pharmacodynamic models using the posterior predictive check.

The posterior predictive check (PPC) is a model evaluation tool. It assigns a value (pPPC) to the probability that the value of a given statistic computed from data arising under an analysis model is as or more extreme than the value computed from the real data themselves. If this probability is too small, the analysis model is regarded as invalid for the given statistic. Properties of the PPC for pharmacokinetic (PK) and pharmacodynamic (PD) model evaluation are examined herein for a particularly simple simulation setting: extensive sampling of a single individual's data arising from simple PK/PD and error models. To test the performance characteristics of the PPC, repeatedly, "real" data are simulated and for a variety of statistics, the PPC is applied to an analysis model, which may (null hypothesis) or may not (alternative hypothesis) be identical to the simulation model. Five models are used here: (PK1) mono-exponential with proportional error, (PK2) biexponential with proportional error, (PK2 epsilon) biexponential with additive error, (PD1) Emax model with additive error under the logit transform, and (PD2) sigmoid Emax model with additive error under the logit transform. Six simulation/analysis settings are studied. The first three, (PK1/PK1), (PK2/PK2), and (PD1/PD1) evaluate whether the PPC has appropriate type-I error level, whereas the second three (PK2/PK1), (PK2 epsilon/PK2), and (PD2/PD1) evaluate whether the PPC has adequate power. For a set of 100 data sets simulated/analyzed under each model pair according to a stipulated extensive sampling design, the pPPC is computed for a number of statistics in three different ways (each way uses a different approximation to the posterior distribution on the model parameters). We find that in general; (i) The PPC is conservative under the null in the sense that for many statistics, prob(pPPC < or = alpha) < alpha for small alpha. With respect to such statistics, this means that useful models will rarely be regarded incorrectly as invalid. A high correlation of a statistic with the parameter estimates obtained from the same data used to compute the statistic (a measure of statistical "sufficiency") tends to identify the most conservative statistics. (ii) Power is not very great, at least for the alternative models we tested, and it is especially poor with "statistics" that are in part a function of parameters as well as data. Although there is a tendency for nonsufficient statistics (as we have measured this) to have greater power, this is by no means an infallible diagnostic. (iii) No clear advantage for one or another method of approximating the posterior distribution on model parameters is found.

Area Under Curve↗

Modified Whittaker plots as an assessment and monitoring tool for vegetation in a lowland tropical rainforest.

Resource exploitation in lowland tropical forests is increasing and causing loss of biodiversity. Effective evaluation and management of the impacts of development on tropical forests requires appropriate assessment and monitoring tools. We propose the use of 0.1-ha multi-scale, modified Whittaker plots (MWPs) to assess and monitor vegetation in lowland tropical rainforests. We established MWPs at 4 sites to: (1) describe and compare composition and structure of the sites using MWPs, (2) compare these results to those of 1-ha permanent vegetation plots (BDPs), and (3) evaluate the ability of MWPs to detect changes in populations (statistical power). We recorded more than 400 species at each site. Species composition among the sites was distinctive, while mean abundance and basal area was similar. Comparisons between MWPs and BDPs show that they record similar species composition and abundance and that both perform equally well at detecting rare species. However, MWPs tend to record more species, and power analysis studies show that MWPs were more effective at detecting changes in the mean number of species of trees > or = 10 cm in diameter at breast height (dbh) and in herbaceous plants. Ten MWPs were sufficient to detect a change of 11% in the mean number of herb species, and they were able to detect a 14% change in the mean number of species of trees > or =10 cm dbh. The value of MWPs for assessment and monitoring is discussed, along with recommendations for improving the sampling design to increase power.

Conservation of Natural Resources↗

Programmable drug delivery from an erodible association polymer system.

An erodible association polymer system based on blends of cellulose acetate phthalate (CAP) and Pluronic F127, a block copolymer of poly(ethylene oxide) and poly(propylene oxide), has been investigated for its applicability to rate-programmed drug delivery. The compatibility and thermal properties were characterized by DSC and FTIR. Results from the thermal analysis indicate that the blends are compatible above 50% CAP, as revealed by a single composition-dependent glass transition temperature (Tg). The existence of molecular association through intermolecular hydrogen bonding between the carboxylic acid and the ether oxygen groups is supported by the observation of an upward shift in the IR carbonyl stretching frequency at increasing Pluronic F127 concentrations. Using theophylline as a model drug, the in vitro polymer erosion and drug release characteristics of the present polymer system were evaluated at different buffer pH's on a rotating-disk apparatus. The results show that the rates of both polymer erosion and drug release increase with the Pluronic F127 concentration in the blend. Further, at pH 4, the polymer erosion is minimal and the theophylline release appears to be governed mainly by diffusion through the polymer matrix. In contrast, at pH 7.4, the theophylline release is controlled primarily by the polymer surface erosion. To demonstrate the unique approach to programmed drug release based on the concept of nonuniform initial drug distribution, pulsatile patterns of drug release have been achieved successfully from the present surface-erodible polymer system using a multilaminate sample design with alternating drug-loaded layers.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Measuring the impact of medicines information services on patient care: methodological considerations.

INTRODUCTION: Medicines information services (MISs) aim to promote the safe, effective and economic use of medicines. Results from published studies suggest that they provide effective information, which in many cases results in improved patient outcome. However, there are several methodological issues that are important in the interpretation of such studies. AIM: To address methodological issues in the evaluation of MISs. OBJECTIVES: To carry out a critical appraisal of papers assessing the impact on patient outcome of passive information given to health care professionals, to identify the key methodological issues and to make recommendations for future research in Europe. METHODS: Literature search to identify relevant papers meeting the inclusion criteria, critical evaluation of the methods used. RESULTS: Most studies have been conducted in the United States. Various methodological considerations were identified: study design, sampling, data collection, choice of outcome measures, and validity. The results of each study are interpreted in view of the methods used. In addition, the implications of the methods selected on the validity, reliability and generalisability of the results are discussed. Finally, suggestions for future studies are provided, in order to maximise validity and reliability.

Drug Information Services↗

Determining working memory from ERP topography.

Event-related potentials were recorded during a delayed matching-to-sample design from 17 volunteers (5 f) using high-resolution (65 channels) EEG-recordings. In the two-stimulus paradigm, the 500-ms stimulus S1 comprised a visual pattern of two diamonds differing in size, angular rotation and location; in the delay period, Working Memory (WM) load was varied in the following way: a stimulus-free interval of 1 s was followed by a 6-s presentation either of a pattern identical to the S1 (low WM load) or of a pattern differing from S1 (high WM load). The 500-ms stimulus S2 comprised one diamond; the subject's task was to indicate by left- or right-hand (respectively) button press, whether the S2 matched the (a) left- or (b) right-positioned S1-diamond, or (c) did not match at all (NoGo). The topographical distribution of activity in the time intervals (a) following S1-offset, (b) during the WM manipulation interval and (c) prior to S2 were evaluated in the signal (scalp potential) and source (Minimum Norm) space. Following S1-offset the ERP pattern was characterised by negativity over posterior areas, slightly more so over the right hemisphere. In the subsequent 6-s interval high WM load elicited a larger negative slow ERP than low WM load, the negativity increase due to high WM load being larger over frontal than central areas. Source modelling indicated activity in anterior areas under high, and posterior activity under low WM load. Asymmetry of activity, although indicating a shift to left-hemispheric activity under high compared to low WM load, varied considerably between subjects. Results suggest that high-resolution ERP recordings allow to examine cortical activity during WM challenge.

Adolescent↗

In search of controlled evidence for health care quality improvement.

The purpose of this study was to measure the efficiency of simple searches in retrieving controlled evidence about specific primary health care quality improvement interventions and their effects. Searches were conducted to retrieve evidence on seven interventions and seven effect variables. Specific words and the closest Medical Subject Headings (MeSH) recommended by professional librarians were used to search the MEDLINE database. Searches were restricted to the MeSH publication type "randomized controlled trial." Two reviewers independently judged retrieved citations for relevancy to the selected interventions and effects. In selecting MeSH terms, the average agreement among librarians was 64.3% (+/-26.1) for interventions and 57.1% (+/-19.9) for effects. Analysis of the 755 retrieved reports showed that MeSH term searches had an overall recall rate of 58% while the same rate for textword searches was significantly lower (11%, p < .001). The difference in overall precision rates was nonsignificant (26% versus 33%, p = .15). In the group of MeSH searches, overall precision and recall was significantly lower for effects than for interventions (12% versus 52%, p < .001 and 41% versus 69%, p < .001). Two textwords appeared in more than 25% of the benchmark collection: reminder (25.7%) and cost (25.0%). The results of this study indicate that information needs for health care quality improvement cannot be met by simple literature searches. Certain MeSH terms and combinations of textwords yield moderately efficient recall and precision in literature searches for health care quality improvement. Clinicians and physician executives gaining direct access to bibliographic database could probably be better served by structured indexing of critical aspects of randomized controlled clinical trials: design, sample, interventions, and effects.

Abstracting and Indexing↗

Acculturation stress, social support, and self-rated health among Latinos in California.

This study looks at the effect of social support mechanisms as potential moderators and mediators of the relationship between stressful acculturation experiences and self-ratings of physical health. Data are from a sample of 3012 Mexican-origin adults aged 18-59 sampled under a probabilistic, stratified, cluster sampling design in Fresno County, California. While acculturation stressors (i.e., discrimination, legal status, and language conflict) all had a gross positive effect on the likelihood of rating oneself in fair/poor health, only legal status stress had a net effect. In addition, greater numbers of peers and family members in the United States, and a higher reliance on religious support mechanisms decreased the likelihood of reporting fair/poor health. However, levels of both instrumental social support and religious support seeking moderated the (nonsignificant, main) effects of discrimination on physical health. This study indicates that physical health is negatively associated with acculturation stressors and positively associated with social support; discrimination is only associated with poorer physical health among those for whom social support is lacking.

Acculturation↗

Epidemiological surveys of autism and other pervasive developmental disorders: an update.

This paper was commissioned by the committee on the Effectiveness of Early Education in Autism of the National Research Council (NRC). It provides a review of epidemiological studies of pervasive developmental disorders (PDD) which updates a previously published article (The epidemiology of autism: a review. Psychological Medicine 1999; 29: 769-786). The design, sample characteristics of 32 surveys published between 1966 and 2001 are described. Recent surveys suggest that the rate for all forms of PDDs are around 30/10,000 but more recent surveys suggest that the estimate might be as high as 60/10,000. The rate for Asperger disorder is not well established, and a conservative figure is 2.5/10,000. Childhood disintegrative disorder is extremely rare with a pooled estimate across studies of 0.2/10,000. A detailed discussion of the possible interpretations of trends over time in prevalence rates is provided. There is evidence that changes in case definition and improved awareness explain much of the upward trend of rates in recent decades. However, available epidemiological surveys do not provide an adequate test of the hypothesis of a changing incidence of PDDs.

Adolescent↗