Distance Properties of Short LDPC Codes and their Impact on the BP, ML and Near-ML Decoding Performance

Parameters of LDPC codes, such as minimum distance, stopping distance, stopping redundancy, girth of the Tanner graph, and their influence on the frame error rate performance of the BP, ML and near-ML decoding over a BEC and an AWGN channel are studied. Both random and structured LDPC codes are considered. In particular, the BP decoding is applied to the code parity-check matrices with an increasing number of redundant rows, and the convergence of the performance to that of the ML decoding is analyzed. A comparison of the simulated BP, ML, and near-ML performance with the improved theoretical bounds on the error probability based on the exact weight spectrum coefficients and the exact stopping size spectrum coefficients is presented. It is observed that decoding performance very close to the ML decoding performance can be achieved with a relatively small number of redundant rows for some codes, for both the BEC and the AWGN channels

Synchronized dynamics of cortical neurons with time-delay feedback

The dynamics of three mutually coupled cortical neurons with time delays in the coupling are explored numerically and analytically. The neurons are coupled in a line, with the middle neuron sending a somewhat stronger projection to the outer neurons than the feedback it receives, to model for instance the relay of a signal from primary to higher cortical areas. For a given coupling architecture, the delays introduce correlations in the time series at the time-scale of the delay. It was found that the middle neuron leads the outer ones by the delay time, while the outer neurons are synchronized with zero lag times. Synchronization is found to be highly dependent on the synaptic time constant, with faster synapses increasing both the degree of synchronization and the firing rate. Analysis shows that presynaptic input during the interspike interval stabilizes the synchronous state, even for arbitrarily weak coupling, and independent of the initial phase. The finding may be of significance to synchronization of large groups of cells in the cortex that are spatially distanced from each other.Comment: 21 pages, 11 figure

Spreading, Nonergodicity, and Selftrapping: a puzzle of interacting disordered lattice waves

Localization of waves by disorder is a fundamental physical problem encompassing a diverse spectrum of theoretical, experimental and numerical studies in the context of metal-insulator transitions, the quantum Hall effect, light propagation in photonic crystals, and dynamics of ultra-cold atoms in optical arrays, to name just a few examples. Large intensity light can induce nonlinear response, ultracold atomic gases can be tuned into an interacting regime, which leads again to nonlinear wave equations on a mean field level. The interplay between disorder and nonlinearity, their localizing and delocalizing effects is currently an intriguing and challenging issue in the field of lattice waves. In particular it leads to the prediction and observation of two different regimes of destruction of Anderson localization - asymptotic weak chaos, and intermediate strong chaos, separated by a crossover condition on densities. On the other side approximate full quantum interacting many body treatments were recently used to predict and obtain a novel many body localization transition, and two distinct phases - a localization phase, and a delocalization phase, both again separated by some typical density scale. We will discuss selftrapping, nonergodicity and nonGibbsean phases which are typical for such discrete models with particle number conservation and their relation to the above crossover and transition physics. We will also discuss potential connections to quantum many body theories.Comment: 13 pages in Springer International Publishing Switzerland 2016 1 M. Tlidi and M. G. Clerc (eds.), Nonlinear Dynamics: Materials, Theory and Experiment, Springer Proceedings in Physics 173. arXiv admin note: text overlap with arXiv:1405.112

Prolonged Exposure to Particulate Pollution, Genes Associated with Glutathione Pathways, and DNA Methylation in a Cohort of Older Men

Background: DNA methylation is a potential pathway linking environmental exposures to disease. Exposure to particulate air pollution has been associated with increased cardiovascular morbidity and mortality, and lower blood DNA methylation has been found in processes related to cardiovascular morbidity

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Biomarkers of Lead Exposure and DNA Methylation within Retrotransposons

Background: DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. Objective: In this study we compared associations between lead biomarkers and DNA methylation. Methods: We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Results: Overall mean global methylation (± SD) was 26.3 ± 1.0 as measured by Alu and 76.8 ± 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (β = −0.25; p less than 0.01) but not Alu (β = −0.03; p = 0.4). Tibia lead and blood lead did not predict global methylation for either Alu or LINE-1. Conclusion: Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Routine testing for IgG antibodies against hepatitis A virus in Israel

BACKGROUND: Viral hepatitis is highly endemic in Israel, with the hepatitis A virus (HAV) responsible for most cases. Improved socioeconomic factors, as well as the universal vaccination of infants (introduced in 1999) has resulted in a decline in infection rates in Israel. This study examines the benefits of routine testing for anti-HAV IgG in high-risk population. METHODS: A retrospective examination of the files of teenage and adult patients (aged 16–99 years; mean 33.9) in two primary care clinics found 1,017 patients who had been tested for anti-HAV IgG antibodies for either general healthcare screening or ongoing follow-up for chronic illness. Seropositive patients were then asked regarding recall of past hepatitis (i.e. jaundice, regardless of viral etiology); post-exposure prophylaxis with immune serum immunoglobulin (ISG); and active immunization with inactivated virus. Seronegative patients were subsequently sent for active immunization. RESULTS: Of the1,017 patient records studied (503 male, 514 female), a total of 692 were seropositive (354 males, 338 females; P = 0.113). Seropositivity rates increased with age (p < 0.005), and were highest among those born in Middle Eastern countries other than Israel (91.3%) and lowest among immigrants from South America (44.1%; P < 0.005). 456 of the seropositive patients were interviewed, of whom only 91 recalled past illness while 103 remembered receiving post-exposure prophylaxis (ISG) and 8 active vaccination. Those who were unaware of past infection were more likely to have been vaccinated with ISG than those who were aware (26.3% vs. 7.7%; p < 0.005). CONCLUSION: The relatively high prevalence rate of anti-HAV seropositivity in our study may me due to the fact that the study was conducted in a primary care clinic or that it took place in Jerusalem, a relatively poor and densely populated Israeli city. Most of the seropostive patients had no recollection of prior infection, which can be explained by the fact that most hepatitis A infections occur during childhood and are asymptomatic. Routine testing for anti-HAV IgG in societies endemic for HAV would help prevent seropositive patients from receiving either post-exposure or preventive immunization and target seronegative patients for preventive vaccination

Factors affecting glomerular filtration rate, as measured by iohexol disappearance, in men with or at risk for HIV infection

Objective: Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design: Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(-)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods: iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results: Median iGFR was higher among HIV(+) than HIV(-) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(-) men; predictors of CKD were similar using iGFR and eGFR. Conclusions: iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR. © 2014 Margolick et al