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Cerebrospinal fluid syndromes in HIV-positive patients with acute consciousness compromise.

We reviewed the cerebrospinal fluid (CSF) syndromes of 100 consecutive HIV-positive patients presenting acute consciousness compromise in emergency rooms, and correlated them with clinical data. The most frequent CSF syndromes were: absolute protein-cytological dissociation (21), viral (19), neurocryptococcosis (7), relative protein-cytological dissociation (6) and septic (4), moderate hypoglycorrachia (4), severe hypoglycorrachia (4) and hydroelectrolytic disturbance (3). One fifth of the patients had CSF syndromes considered sufficient for diagnosis or an immediate clinical decision. The most common clinical data were infective and neurological. There was little correlation between the clinical data and the CSF syndromes. We conclude that in HIV-positive individuals presenting acute consciousness disturbances there are frequently non-specific results in the CSF analysis that must be weighed against a detailed history and thorough physical examination. Taking this into account, in about one fifth of cases the CSF analysis can offer useful information for treatment.

AIDS Dementia Complex↗

Minimum risk weights for comparing treatments in stratified binomial trials.

When comparing two treatments in a stratified trial with a binary endpoint, data are commonly analysed using a weighted averaging of the stratum-specific differences between proportions. Two popular sets of weights are the harmonic means of the stratum-specific sample sizes (SSIZE) and the reciprocals of the variances of the stratum-specific differences (INVAR). Either the SSIZE or INVAR weights are chosen and prespecified in the data analysis plan. We show that the 'wrong' choice between SSIZE and INVAR can result in a significantly inefficient analysis. To circumvent this potential problem, we propose a 'minimum risk' (MR) weighting strategy. The easy-to-compute MR weights are designed to yield more precise and less biased estimates of the overall treatment difference relative to the SSIZE and INVAR weights, respectively. We show, via a simulation study, that the proposed weights are an attractive compromise between the SSIZE and INVAR weights in terms of statistical power. Numerical examples are presented to illustrate the utility of the MR weights.

Anti-Arrhythmia Agents↗

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air has long been used by common cold sufferers. The theoretical basis is that steam may help congested mucus drain better and heat may destroy cold virus as it does in vitro. OBJECTIVES: To assess the effects of inhaling heated water vapour (steam), in the treatment of the common cold by comparing symptoms, viral shedding and nasal resistance. SEARCH STRATEGY: In this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 4, 2005); MEDLINE (2003 to December Week 2 2005); EMBASE (July 2003 to September 2005); and Current Contents (current five years). SELECTION CRITERIA: Randomized controlled trials (RCTs) using heated water vapor in patients with the common cold or volunteers with experimentally induced common cold. DATA COLLECTION AND ANALYSIS: All the articles retrieved were initially subjected to a review for inclusion or exclusion criteria. Review articles, editorials and abstracts with inadequate outcome descriptions were excluded. Studies selected for inclusion were subjected to a methodological assessment. MAIN RESULTS: Six trials were included. Three found benefits of steam for symptom relief with the common cold (odds ratio (OR) 95% confidence interval (CI) 0.31; 0.16 to 0.60; relative risk (RR) 0.56; 95% CI 0.4 to 0.79). Results on symptom indices were equivocal. No studies demonstrated an exacerbation of clinical symptom scores. One USA study demonstrated worsened nasal resistance, while an earlier Israeli one showed improvement. One study examined viral shedding and antibody titres in nasal washings: there was no change of either between treatment and placebo groups. Minor side effects (including discomfort or irritation of the nose) were reported in some studies. AUTHORS' CONCLUSIONS: Steam inhalation are not recommended in the routine treatment of common cold symptoms until more double-blind RCT trials are conducted.

Air↗

Gamma-type endorphins: neurolepticum-like and antipsychotic action.

The hypothesis implicating the gamma-type endorphins in schizophrenia was initially based on animal data showing commonalities between the behavioral effects of these peptides and neuroleptics. Clinical studies have shown that these peptides have an antipsychotic action in a number of patients suffering from schizophrenic psychosis. The patients responding to the peptides are characterized by features at least partly resembling those characterizing type I schizophrenia. This may be consistent with the animal data showing that gamma-type endorphins may directly or indirectly control certain dopaminergic systems present in the nucleus accumbens. Genetical differences may exist between patients susceptible to and not susceptible to gamma-type endorphins, as has been concluded from studies concerning antigens of the HLA system.

Antipsychotic Agents↗

Differential expression of surface monosialoganglioside GM1 in various hemic cell lines of normal human bone marrow. A quantitative immunocytochemical study using the cholera toxin-gold-labeled anti-cholera toxin procedure.

The cholera toxin-colloidal gold-labeled IgG-F(ab')2 anti-cholera toxin ultrastructural immunocytochemical procedure has been used for the localization of GM1 monosialogangliosides on the surface of human bone marrow cells. The number of gold particles per micron of cell surface was counted and the data subjected to statistical analysis. Cholera toxin (CT) binding characteristics assessed in several subjects showed consistent labeling patterns for the various types of marrow cells, although minor quantitative differences were noted in surface labeling densities between subjects. Surface labeling was nonuniformly distributed along the cell membrane of the marrow cells and label clusters or domains were commonly noted. Data analysis indicated that CT labeling was related to cell type, to cell lineage, and to the stage of maturation. Mature neutrophils were the most reactive of the marrow cells and the CT labeling of this cell series increased stepwise from the promyelocyte stage to the segmented neutrophil. A similar pattern occurred during eosinophil maturation and the maturation of the monocyte. A different labeling pattern was found during the differentiation of the erythrocytic cell series with low labeling of proerythroblasts increasing modestly to the early normoblast stage and then decreasing during the final phase of maturation. Exposure to neuraminidase prior to the immunocytochemical sequence induced a major increase in surface CT labeling of the various types of marrow cells, as was particularly evident for the platelet, promyelocyte, myelocyte, monocyte, promonocyte, and erythrocyte cell groups. The data indicated that the number of cryptic GM1 and/or higher gangliosides exposed by neuraminidase in the cell membrane varied during cell differentiation and was directly related to specific cell types. Exogenous GM1 also was demonstrated to be incorporated into the surface of the bone marrow cells in a differential manner and the extent of incorporation was found to be related to specific cell types and to their stage of maturation.

Antitoxins↗

A population-based assessment of left ventricular systolic dysfunction in middle-aged and older adults: the Strong Heart Study.

BACKGROUND: Although clinical congestive heart failure (CHF) is increasingly common, few data document the prevalence and correlates of underlying left ventricular (LV) systolic dysfunction (D) in population-based samples. METHODS: Echocardiography was used in the second Strong Heart Study (SHS) examination to identify mild and severe LVD (LV ejection fraction [EF] 40%-54% and <40%, respectively) in 3184 American Indians. RESULTS: Mild and severe LVD were more common in men than women (17.4% vs 7.2% and 4.7% vs 1.8%) and in diabetic than nondiabetic participants (12.7% vs 9.1% and 3.5% vs 1.6%). Stepwise increases were observed from participants with normal EF to those with mild and severe LVD in age (mean 60 vs 61 and 63 years, P <.001), prevalence of overt CHF (2% vs 6% and 28%) and definite coronary heart disease (3% vs 11% and 32%), systolic pressure (129 vs 135 and 136 mm Hg), serum creatinine level (0.98 vs 1.34 and 2.16 mg/dL), and log urinary albumin/creatinine level (3.2 vs 3.7 and 4.7); a negative relation was seen with body mass index (31.1 vs 31.0 and 28.4 kg/m(2)) (all P <.001). In multivariate analyses lower LVEFs were independently associated with clinical CHF and coronary heart disease, lower myocardial contractility, male sex, hypertension, overweight, arterial stiffening (higher pulse pressure/stroke volume) and renal dysfunction (higher serum creatinine level), higher LV mass, and lower relative wall thickness. CONCLUSIONS: LVD, present in approximately 14% of middle-aged to elderly adults, is independently associated with overt heart failure and coronary heart disease, male sex, hypertension, overweight, arterial stiffening, and renal target organ damage and, less consistently, with older age and diabetes.

Aged↗

Scaling behavior in mitochondrial redox fluctuations.

Scale-invariant long-range correlations have been reported in fluctuations of time-series signals originating from diverse processes such as heart beat dynamics, earthquakes, and stock market data. The common denominator of these apparently different processes is a highly nonlinear dynamics with competing forces and distinct feedback species. We report for the first time an experimental evidence for scaling behavior in NAD(P)H signal fluctuations in isolated mitochondria and intact cells isolated from the liver of a young (5-month-old) mouse. Time-series data were collected by two-photon imaging of mitochondrial NAD(P)H fluorescence and signal fluctuations were quantitatively analyzed for statistical correlations by detrended fluctuation analysis and spectral power analysis. Redox [NAD(P)H / NAD(P)(+)] fluctuations in isolated mitochondria and intact liver cells were found to display nonrandom, long-range correlations. These correlations are interpreted as arising due to the regulatory dynamics operative in Krebs' cycle enzyme network and electron transport chain in the mitochondria. This finding may provide a novel basis for understanding similar regulatory networks that govern the nonequilibrium properties of living cells.

Animals↗

The development and testing of a food portion photograph book for use in an African population.

OBJECTIVE: To develop and test a book of photographs of commonly eaten foods to be used as a visual aid in the description of portion sizes in a large cross-sectional study on the health profile of Africans in transition (THUSA - Transition, Health and Urbanization in South Africa). SETTING: Clinics in the North West Province of South Africa. PARTICIPANTS: One hundred and sixty-nine adult African volunteers DESIGN: Data on commonly eaten foods, preparation methods, recipes and portion sizes were collected in a pilot study. Colour photographs, taken of foods prepared by the researchers and measured into three or four portion sizes, were enlarged and put together in a book. The food portion photograph book (FPPB) was tested by presenting subjects with a portion of real food and asking them to estimate the portion size by matching it with one of the portion photographs. MAIN RESULTS: Of 2959 portions tested, 68% were accurately estimated (estimated weight within 10% of actual weight). Clearly defined solid foods were better estimated than foods that had an amorphous appearance. Accuracy of estimation was not affected by gender, age or education. CONCLUSION: The FPPB was accepted as a useful and convenient visual aid to estimate portion sizes in the cross-sectional dietary intake study.

Journal Article↗

A new scenario for the quaternary history of European beech populations: palaeobotanical evidence and genetic consequences.

Here, palaeobotanical and genetic data for common beech (Fagus sylvatica) in Europe are used to evaluate the genetic consequences of long-term survival in refuge areas and postglacial spread. Four large datasets are presented, including over 400 fossil-pollen sites, 80 plant-macrofossil sites, and 450 and 600 modern beech populations for chloroplast and nuclear markers, respectively. The largely complementary palaeobotanical and genetic data indicate that: (i) beech survived the last glacial period in multiple refuge areas; (ii) the central European refugia were separated from the Mediterranean refugia; (iii) the Mediterranean refuges did not contribute to the colonization of central and northern Europe; (iv) some populations expanded considerably during the postglacial period, while others experienced only a limited expansion; (v) the mountain chains were not geographical barriers for beech but rather facilitated its diffusion; and (vi) the modern genetic diversity was shaped over multiple glacial-interglacial cycles. This scenario differs from many recent treatments of tree phylogeography in Europe that largely focus on the last ice age and the postglacial period to interpret genetic structure and argue that the southern peninsulas (Iberian, Italian and Balkan) were the main source areas for trees in central and northern Europe.

Climate↗

Effects of true density, compacted mass, compression speed, and punch deformation on the mean yield pressure.

Compressibility properties of pharmaceutical materials are widely characterized by measuring the volume reduction of a powder column under pressure. Experimental data are commonly analyzed using the Heckel model from which powder deformation mechanisms are determined using mean yield pressure (Py). Several studies from the literature have shown the effects of operating conditions on the determination of Py and have pointed out the limitations of this model. The Heckel model requires true density and compacted mass values to determine Py from force-displacement data. It is likely that experimental errors will be introduced when measuring the true density and compacted mass. This study investigates the effects of true density and compacted mass on Py. Materials having different particle deformation mechanisms are studied. Punch displacement and applied pressure are measured for each material at two compression speeds. For each material, three different true density and compacted mass values are utilized to evaluate their effect on Py. The calculated variation of Py reaches 20%. This study demonstrates that the errors in measuring true density and compacted mass have a greater effect on Py than the errors incurred from not correcting the displacement measurements due to punch elasticity.

Pressure↗

[Quality assurance in ENT tumor surgery].

BACKGROUND AND OBJECTIVE: Quality control is of special importance in head and neck oncology since the quality of medical care constitutes a vital parameter for the diseased patient. In contrast to other medical specialties, no quality assurance program for head and neck cancer patients has yet been established in Germany. Therefore, a survey was conducted to assess the quality assurance instruments that are in use today in otorhinolaryngology-head and neck (ORL-HNS) centers. PATIENTS AND METHODS: In a nationwide survey, questionnaires were sent out to 146 German ORL-HNS departments (the return rate was 75%). RESULTS: 56% of all departments apply dedicated quality assurance processes, and 38% have appointed a formal quality assurance officer. Interdisciplinary oncological conferences are held in the vast majority of all departments with the participation of radiation oncologists in 86 (78%), medical oncologists in 84 (76%), diagnostic radiologists in 82 (74%), and pathologists in 73 (66%). Morbidity-mortality conferences are held in seven departments (6%). A standardized follow-up of oncological patients is carried out in 95 units (86%), and 53 departments use computer-assisted data bases to organize their follow-up data (48%). A wide variety of documentation systems is in use throughout the country: 78 units (71%) offer formal follow-up to their oncological patients. CONCLUSIONS: This survey documents a wide-spread interest in quality assurance procedures. Many individual efforts are being undertaken. However, no uniform quality assurance or auditing system is currently in use in Germany nor is a commonly accepted data base available. The ability to offer oncological follow-up within the national social security system is generally considered indispensable for the maintenance of high-quality oncological care in ORL-HNS departments.

Germany↗

Reference intervals (normal ranges): a challenge to laboratorians.

Interpretation of laboratory data depends on comparison of individual patient results with reference information from three sources: literature reports, previous results from the patient, and studies conducted in one's own laboratory. Reference data are commonly generated by analyzing specimens from readily available "healthy" subjects, and the results are often used to derive reference intervals which are then given the confusing designation "normal ranges". This paper includes: a review of current practices, recommendations for immediate improvements, and suggestions of future improvements. As acceptable accuracy and precision are established, it will be possible to develop an interlaboratory reference data base. With the developing potential for computer communications, each laboratory could provide reference information relevant to the individual patient, ie, age, sex, body weight, posture, race, diet, physical activity, etc. Not only will reference data be available on "healthy" subjects, but it will be possible to compare patient data with reference intervals associated with specific diseases.

Age Factors↗

Functional MRI experiments: acquisition, analysis and interpretation of data.

Functional MRI is widely used to address basic and clinical neuroscience questions. In the key domains of fMRI experiments, i.e. acquisition, processing and analysis, and interpretation of data, developments are ongoing. The main issues are sensitivity for changes in fMRI signal that are associated with brain function, and the design of tasks with which brain functions are invoked. In this paper we address these issues, in terms of strengths, weaknesses and future developments. Acquisition of data is commonly achieved with techniques that measure blood oxygen level-dependent (BOLD) signal changes. Although the mechanisms that affect BOLD signal are complex and not well understood, fMRI yields results that agree with known functional topography. Sensitivity for task-related brain activity is expected to benefit from technological advances in acquisition, i.e. SENSE or parallel imaging, and higher field scanners (3 T). Data analysis is geared towards modelling sources of signal variation, i.e. reducing noise in the data time-series, and the cerebrovascular response to task-related changes in neuronal activity. Analytical algorithms such as connectivity and component analysis contribute to the extraction of meaningful information from fMRI datasets. The choice of tasks, and consequently of the statistical evaluation procedures, is best guided by the specific questions that are formulated a priori. The future is expected to bring more sophisticated questions, and tasks that allow for accurate modelling of involved brain functions. An example of a hypothesis-driven experiment is presented, where we investigated whether practise of a working memory task caused a shift in the neuronal representation of working memory or not.

Brain↗

Tests for differential gene expression using weights in oligonucleotide microarray experiments.

BACKGROUND: Microarray data analysts commonly filter out genes based on a number of ad hoc criteria prior to any high-level statistical analysis. Such ad hoc approaches could lead to conflicting conclusions with no clear guidance as to which method is most likely to be reproducible. Furthermore, the number of tests performed with concomitant inflation in type I error also plagues the statistical analysis of microarray data, since the number of tested quantities in a study significantly affects the family-wise error rate. It would, therefore, be very useful to develop and adopt strategies that allow quantification of the quality of each probeset, to filter out or give little credence to low-quality or unexpressed probesets, and to incorporate these strategies into gene selection within a multiple testing framework. RESULTS: We have proposed a unified scheme for filtering and gene selection. For Affymetrix gene expression microarrays, we developed new methods for measuring the reliability of a particular probeset in a single array, and we used these to develop measures for a set of arrays. These measures are then used as weights in standard t-statistic calculations, and are incorporated into the multiple testing procedures. We demonstrated the advantages of our methods using simulated data, publicly available spiked-in data as well as data comparing normal muscle to muscle from patients with Duchenne muscular dystrophy (DMD), in which a set of truly differentially expressed genes is known. CONCLUSION: Our quality measures provide convenient ways to search for individual genes of high quality. The quality weighting strategies we proposed for testing differential gene expression have demonstrable improvement on the traditional filtering methods, the standard t-statistic and a regularized t-statistic in Affymetrix data analysis.

Data Interpretation, Statistical↗

Effects and non-effects of paired identical observations in comparing proportions with binary matched-pairs data.

Binary matched-pairs data occur commonly in longitudinal studies, such as in cross-over experiments. Many analyses for comparing the matched probabilities of a particular outcome do not utilize pairs having the same outcome for each observation. An example is McNemar's test. Some methodologists find this to be counterintuitive. We review this issue in the context of subject-specific and population-averaged models for binary data, with various link functions. For standard models and inferential methods, pairs with identical outcomes may affect the estimated size of the effect and its standard error, but they have negligible, if any, effect on significance. We also discuss extension of this result to matched sets.

Logistic Models↗

The effect of litigation status on adjustment to whiplash injury.

STUDY DESIGN: This retrospective study examined the effect of civil litigation on reports of pain and disability in chronic pain patients who sustained whiplash injuries after a motor vehicle accident. OBJECTIVES: To examine the effect of litigation on adjustment to chronic pain. SUMMARY OF BACKGROUND DATA: A common methodologic weakness with many studies in this area is the composition of the nonlitigant group, which often includes individuals who have completed litigation as well as those who opted not to litigate. This introduces a confound in that litigant and nonlitigant groups differ not only with respect to litigation status but with respect to any factors that predispose one to litigate. METHODS: Questionnaire data were obtained from 41 patients (current litigants) in the process of litigation and 21 patients (postlitigants) who had completed litigation. Subjects completed self-report measures assessing demographic characteristics, psychological distress, sleep disturbance, employment status, and various pain indices. RESULTS: There were no significant group differences in demographic characteristics, employment status, or psychological distress. Litigants, however, reported more pain than did postlitigants. Group differences in pain reports remained statistically significant even after controlling for length of time since accident and initial severity of the injuries. CONCLUSIONS: That litigation status did not predict employment status suggests that secondary gain does not figure prominently in influencing the functionality of these patients. The rather robust effect of litigation status on pain reports is discussed with respect to the potential mediational role of the stress of litigation.

Adaptation, Psychological↗

Yomix: an interactive tool for the exploration of low-dimensional embeddings in omics data.

SUMMARY: In the analysis of diverse omics data, a common and important preliminary step involves computing low-dimensional embeddings using techniques such as PCA, UMAP, t-SNE, or variational autoencoders. These embeddings provide a global overview of sample distributions and their relationships, often serving as the basis for formulating biological hypotheses. To facilitate rapid and intuitive exploration of such low-dimensional embeddings, we developed Yomix, an interactive omics-agnostic visualization and data exploration tool. Yomix enables users to flexibly define subsets of interest using a lasso selection tool, instantly compute their feature signatures, and compare their distributions. Yomix is a fast and efficient tool for interactive exploration of diverse omics datasets. AVAILABILITY AND IMPLEMENTATION: Yomix and its documentation are publicly available at https://github.com/perrin-isir/yomix.

Software↗

Inactivation determinants in segment IIIS6 of Ca(v)3.1.

1. Low threshold, T-type, Ca(2+) channels of the Ca(v)3 family display the fastest inactivation kinetics among all voltage-gated Ca(2+) channels. The molecular inactivation determinants of this channel family are largely unknown. Here we investigate whether segment IIIS6 plays a role in Ca(v)3.1 inactivation as observed previously in high voltage-activated Ca(2+) channels. 2. Amino acids that are identical in IIIS6 segments of all Ca(2+) channel subtypes were mutated to alanine (F1505A, F1506A, N1509A, F1511A, V1512A, F1519A, FV1511/1512AA). Additionally M1510 was mutated to isoleucine and alanine. 3. The kinetic properties of the mutants were analysed with the two-microelectrode voltage-clamp technique after expression in Xenopus oocytes. The time constant for the barium current (I(Ba)) inactivation, tau(inact), of wild-type channels at -20 mV was 9.5 +/- 0.4 ms; the corresponding time constants of the mutants ranged from 9.2 +/- 0.4 ms in V1512A to 45.7 +/- 5.2 ms (4.8-fold slowing) in M1510I. Recovery at -80 mV was most significantly slowed by V1512A and accelerated by F1511A. 4. We conclude that amino acids M1510, F1511 and V1512 corresponding to previously identified inactivation determinants in IIIS6 of Ca(v)2.1 (Hering et al. 1998) have a significant role in Ca(v)3.1 inactivation. These data suggest common elements in the molecular architecture of the inactivation mechanism in high and low threshold Ca(2+) channels.

Amino Acid Sequence↗