Reproducibility of CSF quantitative culture methods for estimating rate of clearance in cryptococcal meningitis.

Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in cryptococcal meningitis. The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 participants with meningitis symptoms in Kampala, Uganda, during August-November 2013, 305 CSF samples were prospectively collected from patients at multiple time points during treatment. Samples were simultaneously cultured by three methods: (1) St. George's 100 mcl input volume of CSF with five 1:10 serial dilutions, (2) AIDS Clinical Trials Group (ACTG) method using 1000, 100, 10 mcl input volumes, and two 1:100 dilutions with 100 and 10 mcl input volume per dilution on seven agar plates; and (3) 10 mcl calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods (P= .09) but did for St. George-10 mcl loop (P< .001). Repeated measures pairwise correlation between any of the methods was high (r≥0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91% St. George, 60% loop), but the ACTG-method had occasional (∼10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean -0.05 ± 0.07 log10CFU/ml/day;P= .14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies

Reliability of sickness certificates in detecting potential sick leave reduction by modifying working conditions: a clinical epidemiology study

BACKGROUND: Medical sickness certificates are generally the main source for information when scrutinizing the need for aimed intervention strategies to avoid or reduce the individual and community side effects of sick leave. This study explored the value of medical sickness certificates related to daily work in Norwegian National Insurance Offices to identify sick-listed persons, where modified working conditions might reduce the ongoing sick leave. METHODS: The potential for reducing the ongoing sick leave by modifying working conditions was individually assessed on routine sickness certificates in 999 consecutive sick leave episodes by four Norwegian National Insurance collaborators, two with and two without formal medical competence. The study took place in Northern Norway in 1997 and 1998. Agreement analysed with differences against mean, kappa, and proportional-agreement analysis within and between groups of assessors was used in the judgement. Agreements between the assessors and the self-assessment of sick-listed subjects were additionally analysed in 159 sick-leave episodes. RESULTS: Both sick-listed subjects and National Insurance collaborators anticipated a potential reduction in sick leave in 20–30% of cases, and in another 20% the potential was assessed as possible. The chance corrected agreements, however, were poor (k < 0.20) within and between groups of National Insurance collaborators. The agreement between National Insurance collaborators and the sick-listed subjects was no better than chance. Neither extended medical information nor formal medical competence increased agreement in cases where modified working conditions might have reduced sick leave. CONCLUSION: Information in medical sickness certificates proved ineffective in detecting cases where modified working conditions may reduce sick leave, and focusing on medical certificates may prevent identification of needed interventions. Strategies on how to communicate directly with sick-listed subjects would enable social authorities to exploit more of the sick leave reduction potential by modifying the working conditions than strategies on improving medical information

Correlation between relative rates of hospital treatment or death due to ischaemic heart disease (IHD) and of IHD-related medication among socio-occupational and economic activities groups in Denmark, 1996–2005

Objective: The aim of the present work was to establish whether or not prescribed medication is a usable risk indicator for work‑related ischaemic heart disease (IHD), in Denmark. Material and Methods: Weighted Spearman rank correlation coefficients (rho) were used to evaluate the agreement between Standardised Hazard Ratios (SHR) for hospital treatment or death due to IHD and SHR for purchase of prescriptions for medicine that may prevent IHD from (re)occurring, among socio-occupational and economic activities groups in Denmark. The SHR were based on a 10-year prospective follow-up of 2 million people in Danish national registers 1996–2005. Results: We found approximately 7 times more cases of medicine usage (N = 411 651) than we did for hospital treatment or death (N = 55 684). The correlations between the 2 types of SHR were strong (rho = 0.94 for the socio-occupational groups; rho = 0.74 for the economic activities groups). We observed, however, one markedly contradictive result; the industrial group entitled ‘general practitioner, dentists etc.’ was associated both with significantly high rates of medicine usage (SHR = 1.15, 95% CI: 1.12–1.19) and significantly low rates of hospital treatment or death due to IHD (SHR = 0.80, 95% CI: 0.71–0.91). Conclusion: Apart from a few caveats, the strong correlations obtained in the present study signify that purchase of a prescription for IHD-related medication is a usable risk indicator for IHD in the working population of Denmark. The usage of medicine data in addition to or instead of the use of death or hospital data in epidemiological studies on work-related IHD risk will bring about a tremendous increase in statistical power

Protein Phosphatase 2A Controls Ethylene Biosynthesis by Differentially Regulating the Turnover of ACC Synthase Isoforms

The gaseous hormone ethylene is one of the master regulators of development and physiology throughout the plant life cycle. Ethylene biosynthesis is stringently regulated to permit maintenance of low levels during most phases of vegetative growth but to allow for rapid peaks of high production at developmental transitions and under stress conditions. In most tissues ethylene is a negative regulator of cell expansion, thus low basal levels of ethylene biosynthesis in dark-grown seedlings are critical for optimal cell expansion during early seedling development. The committed steps in ethylene biosynthesis are performed by the enzymes 1-aminocyclopropane 1-carboxylate synthase (ACS) and 1-aminocyclopropane 1-carboxylate oxidase (ACO). The abundance of different ACS enzymes is tightly regulated both by transcriptional control and by post-translational modifications and proteasome-mediated degradation. Here we show that specific ACS isozymes are targets for regulation by protein phosphatase 2A (PP2A) during Arabidopsis thaliana seedling growth and that reduced PP2A function causes increased ACS activity in the roots curl in 1-N-naphthylphthalamic acid 1 (rcn1) mutant. Genetic analysis reveals that ethylene overproduction in PP2A-deficient plants requires ACS2 and ACS6, genes that encode ACS proteins known to be stabilized by phosphorylation, and proteolytic turnover of the ACS6 protein is retarded when PP2A activity is reduced. We find that PP2A and ACS6 proteins associate in seedlings and that RCN1-containing PP2A complexes specifically dephosphorylate a C-terminal ACS6 phosphopeptide. These results suggest that PP2A-dependent destabilization requires RCN1-dependent dephosphorylation of the ACS6 C-terminus. Surprisingly, rcn1 plants exhibit decreased accumulation of the ACS5 protein, suggesting that a regulatory phosphorylation event leads to ACS5 destabilization. Our data provide new insight into the circuitry that ensures dynamic control of ethylene synthesis during plant development, showing that PP2A mediates a finely tuned regulation of overall ethylene production by differentially affecting the stability of specific classes of ACS enzymes

Two-Stage Clustering (TSC): A Pipeline for Selecting Operational Taxonomic Units for the High-Throughput Sequencing of PCR Amplicons

Clustering 16S/18S rRNA amplicon sequences into operational taxonomic units (OTUs) is a critical step for the bioinformatic analysis of microbial diversity. Here, we report a pipeline for selecting OTUs with a relatively low computational demand and a high degree of accuracy. This pipeline is referred to as two-stage clustering (TSC) because it divides tags into two groups according to their abundance and clusters them sequentially. The more abundant group is clustered using a hierarchical algorithm similar to that in ESPRIT, which has a high degree of accuracy but is computationally costly for large datasets. The rarer group, which includes the majority of tags, is then heuristically clustered to improve efficiency. To further improve the computational efficiency and accuracy, two preclustering steps are implemented. To maintain clustering accuracy, all tags are grouped into an OTU depending on their pairwise Needleman-Wunsch distance. This method not only improved the computational efficiency but also mitigated the spurious OTU estimation from ‘noise’ sequences. In addition, OTUs clustered using TSC showed comparable or improved performance in beta-diversity comparisons compared to existing OTU selection methods. This study suggests that the distribution of sequencing datasets is a useful property for improving the computational efficiency and increasing the clustering accuracy of the high-throughput sequencing of PCR amplicons. The software and user guide are freely available at http://hwzhoulab.smu.edu.cn/paperdata/

Chronic hepatitis caused by persistent parvovirus B19 infection

<p>Abstract</p> <p>Background</p> <p>Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions.</p> <p>Case Presentation</p> <p>Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection.</p> <p>Conclusions</p> <p>In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual aetiology of chronic hepatitis, when other causes have been ruled out.</p

Socio-economic inequalities in physical activity practice among Italian children and adolescents: a cross-sectional study

Aim: The aim of the study was to evaluate whether socio-economic inequalities in the practice of physical activity existed among children and adolescents, using different indicators of socio-economic status (SES). Subjects and methods: Data were derived from the Italian National Health Interview Survey carried out in 2004–2005, which examined a large random sample of the Italian population using both an interviewer-administered and a self-compiled questionnaire. This study was based on a sample of 15,216 individuals aged 6–17 years. The practice of physical activity was measured on the basis of questions regarding frequency and intensity of activity during leisure time over the past 12 months. Parents’ educational and occupational level, as well as family’s availability of material resource, were used as indicators of SES. Multivariable logistic regression analyses were performed to estimate the contribution of each SES indicator to the practice of physical activity, adjusting for potential confounding factors. The results of the regression models are expressed as odds ratio (OR) with 95% confidence intervals (95% CI). Results: About 64% of children and adolescents in the sample declared that they participated in moderate or vigorous physical activity at least once a week. After adjustment for gender, age, parental attitudes towards physical activity and geographical area, the practice of physical activity increased with higher parental educational and occupational level and greater availability of material resources. Children and adolescents whose parents held a middle or high educational title were 80% more likely to practice moderate or vigorous physical activity than subjects whose parents had a lower level of education (OR = 1.80, 95% CI: 1.40–2.33), while subjects with unemployed parents had an odds of practicing moderate or vigorous physical activity 0.43 times that of those children whose parents belonged to the top job occupation category (administrative/professionals). Socio-economic differences were about the same when the practice of vigorous physical activity only was considered instead of that of moderate or vigorous physical activity. Conclusion: Interventions that promote the practice of physical activity, and especially those aimed at the wider physical and social environment, are strongly needed to contrast socio-economic differences in physical activity among children and adolescents

Variation in styles of rifting in the Gulf of California

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 466-469, doi:10.1038/nature06035.The rifting of continental lithosphere is a fundamental solid-earth process that leads to the formation of rifted continental margins and ocean basins. Understanding of this process comes from observations of the geometry of rifted margins and the magmatism resulting from rifting, which inform us about the strength of the lithosphere, the state of the underlying mantle, and the transition from rifting to seafloor spreading. Here we describe results from the PESCADOR seismic experiment in the southern Gulf of California and present the first crustal-scale images across conjugate margins of multiple segments within a single rift that has reached the stage of oceanic spreading. A surprisingly large variation in rifting style and magmatism is observed between these segments, from wide rifting with minor syn-rift magmatism to narrow rifting in magmatically robust segments. These differences encompass much of the variation observed across nearly all other non-end-member continental margins. The characteristics of magmatic endmember margins are typically explained in terms of mantle temperature. Our explanations for the variation in the Gulf of California, in contrast, invoke mantle depletion to account for wide, magma-poor rifting and mantle fertility and possibly the influence of sediments to account for robust rift and post-rift magmatism in the Gulf of California. These factors may vary laterally over small distances in regions that have transitioned from convergence to extension, as is the case for the Gulf of California and many other rifts.This work was funded by a grant from the U.S. NSF-MARGINS program

Mixed emotions to near-miss outcomes: a psychophysiological study with facial electromyography

Near-misses occur across many forms of gambling and are rated as unpleasant while simultaneously increasing the motivation to continue playing. On slot machines, the icon position relative to the payline moderates the effects of near-misses, with near-misses before the payline increasing motivation, and near-misses after the payline being rated as aversive. Near-misses are also known to increase physiological arousal compared to full-misses, but physiological measures to date have not been able to dissociate positive and negative emotional responses. The present study measured facial electromyography at the corrugator (brow) and zygomaticus (cheek) sites, as well as electrodermal activity (EDA), following gambling outcomes on a two-reel slot machine simulation in 77 novice gamblers. Behavioral data was collected using trial-by-trial ratings of motivation and valence. Wins were rated as more pleasant and increased motivation to continue playing, compared to non-win outcomes. Wins were also accompanied by increased EDA and zygomaticus activity. Near-misses after the payline were rated as more aversive than other non-wins, and this was accompanied by increased EDA and zygomaticus activity. Near-misses before the payline increased motivation to continue playing, and were accompanied by increased EDA. Thus, both subjective and physiological responses to near-misses differ for events falling either side of the payline. The ‘near-miss effect’ is not a unitary phenomenon. Facial EMG has differential sensitivity to positive and negative valence and may be a useful measure for future studies of gambling behavior

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff