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Concept: Non-parametric statistics

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The purpose of this study was to evaluate the visual outcome of chronic occupational exposure to a mixture of organic solvents by measuring color discrimination, achromatic contrast sensitivity and visual fields in a group of gas station workers. We tested 25 workers (20 males) and 25 controls with no history of chronic exposure to solvents (10 males). All participants had normal ophthalmologic exams. Subjects had worked in gas stations on an average of 9.6 ± 6.2 years. Color vision was evaluated with the Lanthony D15d and Cambridge Colour Test (CCT). Visual field assessment consisted of white-on-white 24-2 automatic perimetry (Humphrey II-750i). Contrast sensitivity was measured for sinusoidal gratings of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0 and 20.0 cycles per degree (cpd). Results from both groups were compared using the Mann-Whitney U test. The number of errors in the D15d was higher for workers relative to controls (p<0.01). Their CCT color discrimination thresholds were elevated compared to the control group along the protan, deutan and tritan confusion axes (p<0.01), and their ellipse area and ellipticity were higher (p<0.01). Genetic analysis of subjects with very elevated color discrimination thresholds excluded congenital causes for the visual losses. Automated perimetry thresholds showed elevation in the 9°, 15° and 21° of eccentricity (p<0.01) and in MD and PSD indexes (p<0.01). Contrast sensitivity losses were found for all spatial frequencies measured (p<0.01) except for 0.5 cpd. Significant correlation was found between previous working years and deutan axis thresholds (rho = 0.59; p<0.05), indexes of the Lanthony D15d (rho=0.52; p<0.05), perimetry results in the fovea (rho= -0.51; p<0.05) and at 3, 9 and 15 degrees of eccentricity (rho= -0.46; p<0.05). Extensive and diffuse visual changes were found, suggesting that specific occupational limits should be created.

Concepts: Mann–Whitney U, Non-parametric statistics, Vision, Visual perception, Visual system, Ophthalmology, Visual field, Ellipse

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BACKGROUND: Antibody opsonization of Plasmodium falciparum-infected erythrocytes (IE) plays a crucial role in anti-malarial immunity by promoting clearance of blood-stage infection by monocytes and macrophages. The effects of phagocytosis of opsonized IE on macrophage proinflammatory cytokine responses are poorly understood. METHODS: Phagocytic clearance, cytokine response and intracellular signalling were measured using IFN-gamma-primed human monocyte-derived macrophages (MDM) incubated with opsonized and unopsonized trophozoite-stage CS2 IE, a chondroitin sulphate-binding malaria strain. Cytokine secretion was measured by bead array or ELISA, mRNA using quantitative PCR, and activation of NF-kappaB by Western blot and electrophoretic mobility shift assay. Data were analysed using the Mann-Whitney U test or the Wilcoxon signed rank test as appropriate. RESULTS: Unopsonized CS2 IE were not phagocytosed whereas IE opsonized with pooled patient immune serum (PPS) were (Phagocytic index (PI)=18.4, [SE 0.38] n=3). Unopsonized and opsonized IE induced expression of TNF, IL-1beta and IL-6 mRNA by MDM and activated NF- kappaB to a similar extent. Unopsonized IE induced secretion of IL-6 (median= 622 pg/ml [IQR=1,250-240], n=9) but no IL-1beta or TNF, whereas PPS-opsonized IE induced secretion of IL-1beta (18.6 pg/mL [34.2-14.4]) and TNF (113 pg/ml [421-17.0]) and increased IL-6 secretion (2,195 pg/ml [4,658-1,095]). Opsonized, but not unopsonized, CS2 IE activated caspase-1 cleavage and enzymatic activity in MDM showing that Fc receptor-mediated phagocytosis activates the inflammasome. MDM attached to IgG-coated surfaces however secreted IL-1beta in response to unopsonized IE, suggesting that internalization of IE is not absolutely required to activate the inflammasome and stimulate IL-1beta secretion. CONCLUSIONS: It is concluded that IL-6 secretion from MDM in response to CS2 IE does not require phagocytosis, whereas secretion of TNF and IL-1beta is dependent on Fcgamma receptor-mediated phagocytosis; for IL-1beta, this occurs by activation of the inflammasome. The data presented in this paper show that generating antibody responses to blood-stage malaria parasites is potentially beneficial both in reducing parasitaemia via Fcgamma receptor-dependent macrophage phagocytosis and in generating a robust pro-inflammatory response.

Concepts: Immune system, Inflammation, Antibody, Phagocytosis, Apoptosis, Mann–Whitney U, Non-parametric statistics, Opsonin

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BACKGROUND: Mycobacterium tuberculosis encodes 11 putative serine-threonine proteins Kinases (STPK) which regulates transcription, cell development and interaction with the host cells. From the 11 STPKs three kinases namely PknA, PknB and PknG have been related to the mycobacterial growth. From previous studies it has been observed that PknB is essential for mycobacterial growth and expressed during log phase of the growth and phosphorylates substrates involved in peptidoglycan biosynthesis. In recent years many high affinity inhibitors are reported for PknB. Previously implementation of data fusion has shown effective enrichment of active compounds in both structure and ligand based approaches .In this study we have used three types of data fusion ranking algorithms on the PknB dataset namely, sum rank, sum score and reciprocal rank. We have identified reciprocal rank algorithm is capable enough to select compounds earlier in a virtual screening process. We have also screened the Asinex database with reciprocal rank algorithm to identify possible inhibitors for PknB. RESULTS: In our work we have used both structure-based and ligand-based approaches for virtual screening, and have combined their results using a variety of data fusion methods. We found that data fusion increases the chance of actives being ranked highly. Specifically, we found that the ranking of Pharmacophore search, ROCS and Glide XP fused with a reciprocal ranking algorithm not only outperforms structure and ligand based approaches but also capable of ranking actives better than the other two data fusion methods using the BEDROC, robust initial enhancement (RIE) and AUC metrics. These fused results were used to identify 45 candidate compounds for further experimental validation. CONCLUSION: We show that very different structure and ligand based methods for predicting drug-target interactions can be combined effectively using data fusion, outperforming any single method in ranking of actives. Such fused results show promise for a coherent selection of candidates for biological screening.

Concepts: Adenosine triphosphate, Enzyme, Tuberculosis, Non-parametric statistics, Mycobacterium, Mycobacterium tuberculosis, Ranking, RANK

164

Obesity has been associated with respiratory complications, and the majority of these complications occur in the Post-Anesthesia Care Unit (PACU). The aim of this study was to evaluate the outcome and incidence of adverse respiratory events (AREs) in obese patients during their stay in the PACU METHODS: We conducted a prospective control study that included 27 obese patients matched with an equal number of patients with body mass index (BMI)<30 (non-obese control group); the 2 groups of patients were similar in respect to gender distribution, age, and type of surgery and had been admitted into the PACU after elective surgery (May 2011). The AREs were identified during PACU stay. Descriptive analysis of variables was performed, and the Mann-Whitney U test, Chi-square test, or Fisher's exact test were used for comparisons. Associations with AREs were studied using univariate and multivariate logistic regression models.

Concepts: Statistical tests, Statistics, Body mass index, Mann–Whitney U, Non-parametric statistics, Fisher's exact test, Chi-square test, Categorical data

162

Hypersensitivity to DNaseI digestion is a hallmark of open chromatin and DNaseI-seq allows the genome-wide identification of regions of open chromatin. Interpreting these data is challenging, largely because of inherent variation in signal-to-noise ratio (SNR) between datasets. We have developed PeaKDEck, a peak calling program that distinguishes signal from noise by randomly sampling read densities and employing kernel density estimation to generate a dataset-specific probability distribution of random background signal. PeaKDEck uses this probability distribution to select an appropriate read density threshold for peak calling in each dataset. We benchmark PeaKDEck using published ENCODE DNaseI-seq data, and other peak calling programs, and demonstrate superior performance in low SNR datasets.Availability and implementation: PeaKDEck is written in standard Perl and runs on any platform with Perl installed. PeaKDEck is also available as a standalone application written in Perl/Tk, which does not require Perl to be installed. Files, including a user guide can be downloaded at: www.ccmp.ox.ac.uk/peakdeck CONTACT: chris.ocallaghan@ndm.ox.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Concepts: Statistics, Data, Non-parametric statistics, Probability density function, Random variable, Histogram, Signal-to-noise ratio, Kernel density estimation

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This paper finds that a 10-μg/m(3) increase in airborne particulate matter [particulate matter smaller than 10 μm (PM10)] reduces life expectancy by 0.64 years (95% confidence interval = 0.21-1.07). This estimate is derived from quasiexperimental variation in PM10 generated by China’s Huai River Policy, which provides free or heavily subsidized coal for indoor heating during the winter to cities north of the Huai River but not to those to the south. The findings are derived from a regression discontinuity design based on distance from the Huai River, and they are robust to using parametric and nonparametric estimation methods, different kernel types and bandwidth sizes, and adjustment for a rich set of demographic and behavioral covariates. Furthermore, the shorter lifespans are almost entirely caused by elevated rates of cardiorespiratory mortality, suggesting that PM10 is the causal factor. The estimates imply that bringing all of China into compliance with its Class I standards for PM10 would save 3.7 billion life-years.

Concepts: Statistics, Estimator, Non-parametric statistics, Life expectancy, Particulate, Smog, Statistical inference, Air pollution

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Previous electromyographic (EMG) studies of gluteus medius (GMed) have not accurately quantified the function of the three proposed structurally and functionally unique segments (anterior, middle and posterior). Therefore this study used anatomically verified locations for intramuscular electrode recordings in three segments of GMed to determine whether the segments are functionally independent. Bipolar fine wire electrodes were inserted into each segment of GMed in 15 healthy individuals. Participants completed a series of four walking trials, followed by maximum voluntary isometric contractions (MVICs) in five different positions. Temporal and amplitude variables for each segment were compared across the gait cycle using ANOVA. The relative contributions of each segment to the MVIC trials were compared with non-parametric tests. All segments showed a biphasic response during the stance phase of gait. There were no differences in amplitude variables (% MVIC) between segments, but the anterior segment had a later peak during both the first and second bursts.For the MVIC trials, there were significant differences in amplitude between segments in four of the five test positions. These data indicate that GMed is composed of three functionally independent segments. This study contributes to the theoretical understanding of the role of GMed.

Concepts: Electroencephalography, Non-parametric statistics, Electromyography, Electrode, Segment, Isometric exercise, Gluteal muscles, Gluteus medius muscle

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Study Design. A descriptive study of the association between demographic factors, and physical characteristics, and degenerative lumbar spinal stenosis (DLSS).Objective. To shed light on the association of socioeconomic parameters and physical characteristics with DLSS.Summary of Background Data. Lumbar spinal stenosis is a prevalent and disabling condition in the aging population. DLSS is considered to be the most common type and is essentially associated with disc disease, facet joint arthrosis, ligamentum flavum thickening and osteophyte formation. While there is ample information regarding the association between BMI, cardiovascular disorders, smoking habits and disc disease, very little is known about their association with DLSS. Data on the association of body physique (e.g., height and weight) and DLSS are limited.Methods. Two sample populations were studied. The first included 165 individuals with DLSS (mean age 64 ± 9.9 years) and the second 180 individuals without spinal stenosis related symptoms (mean age 62.5 ± 12.6 years). An evaluation of the cross-sectional area of the dural sac and degenerative listhesis for all participants was performed on CT lumbar spine images, utilizing Philips EBW station (Brilliance 64, Philips Medical System, Cleveland Ohio). All participants were interviewed in order to obtain demographic, physical and health data. Independent T- test, Mann-Whitney and Chi-square tests were used to determine the association between parametric and non-parametric variables and DLSS. Logistic regression analysis was carried out in order to reveal predicting variables for DLSS.Results. Stenosis females were significantly heavier and shorter compared to their counterparts in the control group. We also noticed that they delivered babies more often than those in the control group. Prevalence of individuals suffering from diabetes mellitus was significantly higher in the stenosis males compared to control group. In the stenosis group, the frequencies of individuals engaged in heavy manual labor (males) and housekeeping (females) were significantly higher compared to their counterparts in the control group.Conclusions. Heavy manual labor and diabetes mellitus in males and housekeeping (females) play major roles in the genesis of DLSS.

Concepts: Regression analysis, Logistic regression, Disease, Diabetes mellitus, Demography, Population, Non-parametric statistics, Spinal stenosis

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Context:Clinicians who prescribe levothyroxine (LT4) for hypothyroidism often feel strongly about using a brand-name drug instead of a generic.Objective:The objective of the study was to determine whether Synthroid resulted in better control of congenital hypothyroidism than generic LT4.Design:This was a 5-year retrospective study.Setting:The study was conducted at 1 tertiary care center.Patients:Children who were 0-36 months old with congenital hypothyroidism followed up at our center from 2006 to 2011 were treated with either Synthroid exclusively (35 subjects) or generic LT4 exclusively (27 subjects).Interventions:We recorded the subjects' TSH and free T(4) measurements, how often their LT4 dose was adjusted, and the duration of follow-up.Main Outcome Measure:TSH variance between the groups was measured. Secondary end points were the frequency of LT4 dose changes and the variance in free T4.Results:Using the Wilcoxon rank sum test, there was no difference in TSH SD in the Synthroid group compared with the generic group (median 3.0 vs 2.2, P = .27). Using a linear mixed model, children treated with the generic LT4 had lower TSH estimated SD [1.35 with 95% confidence interval (CI) (1.194, 1.526)] than the Synthroid group [1.66 with 95% CI (1.536, 1.803)]. Similarly, no difference was observed in free T(4) SD between the groups using the Wilcoxon rank sum test (median 0.29 generic vs 0.36 Synthroid, P = .11), but the generic group had lower free T(4) estimated SD than the Synthroid group using the linear mixed model [0.216 with 95% CI (0.187, 0.249) vs 0.298 with 95% CI (0.273,0.326)]. Frequency of LT4 dosing adjustments was similar between the groups, both in total (median 2.0 for generic vs 3.0 for Synthroid, P = .097) and when adjusted for number of TSH checks (ratio 0.25 generic vs 0.31 Synthroid, P = .45).Conclusions:In our study of congenital hypothyroidism, generic LT4 treatment resulted in similar or better control of hypothyroidism compared with Synthroid, as assessed by the clinical outcomes of TSH variance and the frequency of LT4 dosing adjustments.

Concepts: Statistics, Measurement, Mann–Whitney U, Non-parametric statistics, Hypothyroidism, Normal distribution, Wilcoxon signed-rank test, Levothyroxine

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OBJECTIVES: Neurofibromatosis 1 (NF1), NF2, and schwannomatosis are characterized by a predisposition to develop multiple neurofibromas and schwannomas. Currently, there is no blood test to estimate tumor burden in patients with these disorders. We explored whether S100β would act as a biomarker of tumor burden in NF since S100β is a classic immunohistochemical marker of astrocytes, oligodendrocytes and Schwann cells and a small study showed S100β concentrations correlate with the volume of vestibular schwannomas. Design and Methods We calculated whole-body tumor burden in subjects with NF1, NF2, and schwannomatosis using whole-body MRI (WBMRI) and measured the concentration of S100β in plasma using ELISA. We used chi-square tests and Spearman rank correlations to test the relationship between S100β levels and whole-body tumor burden. RESULTS: 127 consecutive patients were enrolled in the study (69 NF1 patients, 28 NF2 patients, and 30 schwannomatosis patients). The median age was 40years, 43% were male, median whole-body tumor volume was 26.9ml. There was no relationship between the presence of internal tumors and the presence of detectable S100β in blood for the overall group or for individual diagnoses (p>0.05 by chi-square for all comparisons). Similarly, there was no correlation between whole-body tumor volume and S100β concentration for the overall group or for individual diagnoses (p>0.05 by Spearman for all comparisons). CONCLUSIONS: Plasma S100β is not a useful biomarker for tumor burden in the neurofibromatoses. Further work is needed to identify a reliable biomarker of tumor burden in NF patients.

Concepts: Blood, Spearman's rank correlation coefficient, Neurology, Non-parametric statistics, Correlation and dependence, Pearson product-moment correlation coefficient, Neurofibromatosis, Neurofibroma