Desynchronizing effect of high-frequency stimulation in a generic cortical network model

Transcranial Electrical Stimulation (TCES) and Deep Brain Stimulation (DBS) are two different applications of electrical current to the brain used in different areas of medicine. Both have a similar frequency dependence of their efficiency, with the most pronounced effects around 100Hz. We apply superthreshold electrical stimulation, specifically depolarizing DC current, interrupted at different frequencies, to a simple model of a population of cortical neurons which uses phenomenological descriptions of neurons by Izhikevich and synaptic connections on a similar level of sophistication. With this model, we are able to reproduce the optimal desynchronization around 100Hz, as well as to predict the full frequency dependence of the efficiency of desynchronization, and thereby to give a possible explanation for the action mechanism of TCES.Comment: 9 pages, figs included. Accepted for publication in Cognitive Neurodynamic

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

Background: Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design: The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion: The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy. Trial registration: Trial registration number NTR2774

Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1

The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial

BACKGROUND: Patellar tendinopathy is a major problem for many athletes, especially those involved in jumping activities. Despite its frequency and negative impact on athletic careers, no evidence-based guidelines for management of this overuse injury exist. Since functional outcomes of conservative and surgical treatments remain suboptimal, new diagnostic and therapeutic strategies have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment in patients with chronic patellar tendinopathy. ESWT is most often applied after the known conservative treatments have failed. However, its effectiveness as primary therapy has not been studied in athletes who keep playing sports despite having patellar tendon pain. The aim of this study is to determine the effectiveness of ESWT in athletes with patellar tendinopathy who are still in training and competition. METHODS/DESIGN: The TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a multicentre two-armed randomised controlled trial with blinded participants and outcome assessors, in which the effectiveness of patient-guided focussed ESWT treatment (compared to placebo ESWT) on pain reduction and recovery of function in athletes with patellar tendinopathy will be investigated. Participants are volleyball, handball and basketball players with symptoms of patellar tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still able to train and compete. The intervention group receives three patient-guided focussed medium-energy density ESWT treatments without local anaesthesia at a weekly interval in the first half of the competition. The control group receives placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after the final ESWT or placebo treatment, when athletes are still in competition. Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment - patella) score. Data with regard to pain during function tests (jump tests and single-leg decline squat) and ultrasound characteristics are also collected. During the follow-up period participants also register pain, symptoms, sports participation, side effects of treatment and additional medical consumption in an internet-based diary. DISCUSSION: The TOPGAME-study is the first RCT to study the effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who are still in training and competition. TRIAL REGISTRATION: Trial registration number NTR1408

Non-Parametric Change-Point Method for Differential Gene Expression Detection

We proposed a non-parametric method, named Non-Parametric Change Point Statistic (NPCPS for short), by using a single equation for detecting differential gene expression (DGE) in microarray data. NPCPS is based on the change point theory to provide effective DGE detecting ability.NPCPS used the data distribution of the normal samples as input, and detects DGE in the cancer samples by locating the change point of gene expression profile. An estimate of the change point position generated by NPCPS enables the identification of the samples containing DGE. Monte Carlo simulation and ROC study were applied to examine the detecting accuracy of NPCPS, and the experiment on real microarray data of breast cancer was carried out to compare NPCPS with other methods.Simulation study indicated that NPCPS was more effective for detecting DGE in cancer subset compared with five parametric methods and one non-parametric method. When there were more than 8 cancer samples containing DGE, the type I error of NPCPS was below 0.01. Experiment results showed both good accuracy and reliability of NPCPS. Out of the 30 top genes ranked by using NPCPS, 16 genes were reported as relevant to cancer. Correlations between the detecting result of NPCPS and the compared methods were less than 0.05, while between the other methods the values were from 0.20 to 0.84. This indicates that NPCPS is working on different features and thus provides DGE identification from a distinct perspective comparing with the other mean or median based methods

Neighborhood Socioeconomic Status and Use of Colonoscopy in an Insured Population – A Retrospective Cohort Study

Background: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. Methods We assembled a retrospective cohort of 100,566 men and women, 50–74 years old, who had been enrolled in one of three US health plans for $\geq$ 1 year on January 1, 2000. Subjects were followed until the date of first colonoscopy, date of disenrollment from the health plan, or December 31, 2007, whichever occurred first. We obtained data on colonoscopy use from administrative records. We defined screening colonoscopy as an examination that was not preceded by gastrointestinal conditions in the prior 6-month period. Neighborhood SES was measured using the percentage of households in each subject's census-tract with an income below 1999 federal poverty levels based on 2000 US census data. Analyses, adjusted for demographics and comorbidity index, were performed using Weibull regression models. Results: The average age of the cohort was 60 years and 52.7% were female. During 449,738 person-years of follow-up, fewer subjects in the lowest SES quartile (Q1) compared to the highest quartile (Q4) had any colonoscopy (26.7% vs. 37.1%) or a screening colonoscopy (7.6% vs. 13.3%). In regression analyses, compared to Q4, subjects in Q1 were 16% (adjusted HR = 0.84, 95% CI: 0.80–0.88) less likely to undergo any colonoscopy and 30%(adjusted HR = 0.70, CI: 0.65–0.75) less likely to undergo a screening colonoscopy. Conclusion: People in lower-SES neighborhoods are less likely to undergo a colonoscopy, even among insured subjects receiving care in integrated healthcare systems. Removing health insurance barriers alone is unlikely to eliminate disparities in colonoscopy use

Genome-wide inference of regulatory networks in Streptomyces coelicolor

Background: The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. Results: In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Conclusions: Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

In-home solid fuel use and cardiovascular disease: a cross-sectional analysis of the Shanghai Putuo study

Background: Although recent research evidence suggests an association between household air pollution from solid fuel use, such as coal or biomass, and cardiovascular events such as hypertension, little epidemiologic data are available concerning such exposure effects on cardiovascular endpoints other than hypertension. We explored the association between in-home solid fuel use and self-reported diagnoses of cardiovascular endpoints, such as hypertension, coronary heart disease (CHD), stroke, and diabetes. Methods: We analyzed 14,068 Chinese adults, aged 18 years and older. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using logistic regression models for the risk of each outcome after adjusting for potential confounders. Results: The use of solid fuel in home was significantly associated with an increased risk for hypertension (OR 1.70, 95% CI 1.40 to 2.07), CHD (OR 2.58, 95% CI 1.53 to 4.32), and diabetes (OR 2.48, 95% CI 1.59 to 3.86), after adjusting for potential confounders. Compared with individuals in the lowest tertile of the duration of solid fuel exposure, those in the highest tertile of the duration of solid fuel exposure had an increased odds of hypertension (OR 1.73, 95% CI 1.45 to 2.06), stroke (OR 1.87, 95% CI 1.03 to 3.38), and diabetes (OR 3.18, 95% CI 2.11 to 4.78). Conclusions: Our data suggest that in-home solid fuel exposure maybe associated with increased risk for hypertension, CHD, stroke, and diabetes in the Chinese adult population. Further large-scale longitudinal studies are warranted to confirm these findings

Genetic Diversity of Dahongjun, the Commercially Important “Big Red Mushroom” from Southern China

BACKGROUND: In southern China, a wild ectomycorrhizal mushroom commonly called "Dahongjun" or "Big Red Mushroom" by the local residents, has been harvested, consumed, and/or exported as an exotic food for many years. Although ecologically and economically important, very little is known about this mushroom, including its diversity and population structure. METHODOLOGY AND PRINCIPAL FINDINGS: In this study, we analyzed 122 samples from five local populations representing the known distribution ranges of this mushroom in southern China. We investigated the genetic diversity and geographic structure of this mushroom using sequences from four DNA fragments. Our analyses identified that this mushroom contained at least three divergent lineages: one corresponds to a recently described species Russula griseocarnosa from southern China and the remaining two likely represent two novel species. While these lineages were prominently structured geographically based on ITS sequences, evidence for ancient and/or recent gene flow was also identified within individual lineages. In addition, a local population from Ailaoshan in central Yunnan Province where 85 of our 122 specimens came from showed clear evidence of recombination. CONCLUSION AND SIGNIFICANCE: The ectomycorrhizal mushroom "Dahongjun" from southern China is a species complex with at least three divergent lineages. These lineages are largely geographically structured and there is evidence for recombination in nature. Our results indicate mature Dahongjun mushrooms with abundant basidiospores are important for the reproduction of this mushroom in nature and that individual populations of this species should be managed separately

Area-level poverty and preterm birth risk: A population-based multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate.</p> <p>Methods</p> <p>Population-based study utilizing Missouri's birth certificate database (1989–1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line (US census data, 1990). Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group.</p> <p>Results</p> <p>PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4^thquartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (_adjOR) 1.18 (95% CI 1.03, 1.35), with a similar effect at earlier gestational ages (< 32 weeks), _adjOR 1.27 (95% CI 1.06, 1.52).</p> <p>Conclusion</p> <p>Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies.</p