Scaling Reliably: Improving the Scalability of the Erlang Distributed Actor Platform

Distributed actor languages are an effective means of constructing scalable reliable systems, and the Erlang programming language has a well-established and influential model. While the Erlang model conceptually provides reliable scalability, it has some inherent scalability limits and these force developers to depart from the model at scale. This article establishes the scalability limits of Erlang systems and reports the work of the EU RELEASE project to improve the scalability and understandability of the Erlang reliable distributed actor model. We systematically study the scalability limits of Erlang and then address the issues at the virtual machine, language, and tool levels. More specifically: (1) We have evolved the Erlang virtual machine so that it can work effectively in large-scale single-host multicore and NUMA architectures. We have made important changes and architectural improvements to the widely used Erlang/OTP release. (2) We have designed and implemented Scalable Distributed (SD) Erlang libraries to address language-level scalability issues and provided and validated a set of semantics for the new language constructs. (3) To make large Erlang systems easier to deploy, monitor, and debug, we have developed and made open source releases of five complementary tools, some specific to SD Erlang. Throughout the article we use two case studies to investigate the capabilities of our new technologies and tools: a distributed hash table based Orbit calculation and Ant Colony Optimisation (ACO). Chaos Monkey experiments show that two versions of ACO survive random process failure and hence that SD Erlang preserves the Erlang reliability model. While we report measurements on a range of NUMA and cluster architectures, the key scalability experiments are conducted on the Athos cluster with 256 hosts (6,144 cores). Even for programs with no global recovery data to maintain, SD Erlang partitions the network to reduce network traffic and hence improves performance of the Orbit and ACO benchmarks above 80 hosts. ACO measurements show that maintaining global recovery data dramatically limits scalability; however, scalability is recovered by partitioning the recovery data. We exceed the established scalability limits of distributed Erlang, and do not reach the limits of SD Erlang for these benchmarks at this scal

Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

<p>Abstract</p> <p>Background</p> <p>In settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON^®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed.</p> <p>Methods</p> <p>From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed.</p> <p>Results</p> <p>Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 10⁹/L vs. 8.8 × 10⁹/L; <it>P </it>< 0.001) and a higher median body mass index (22.7 vs. 20.7; <it>P </it>= 0.043) as compared to QFT-G-negative TB patients.</p> <p>Conclusion</p> <p>The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was observed for extrapulmonary TB and QFT-G might be considered in the diagnostic process in this situation. The PPV and NPV for identifying active TB among persons originating from regions with high-and intermediate TB incidence was similar to that observed in subjects originating in the low-incidence region.</p

Prevalence of challenging behaviour in adults with intellectual disabilities, correlates, and association with mental health

Purpose of Review To summarise findings about the prevalence and correlates of challenging behaviour in adults with intellectual disabilities from robust research. We also describe findings on the interplay between challenging behaviour and mental health. Recent Findings Recent studies that have utilised psychometrically evaluated tools, with clear operational definitions, show similar findings on the prevalence of challenging behaviour of about 1 in every 5–6 adults known to services. We describe common correlates identified such as communication impairments, severity of intellectual disability, and living in institutional settings or congregate care. We also describe the complex and multifaceted relationship between challenging behaviour and mental health. Summary Based on recent studies, we propose a revised framework model to help understand challenging behaviour. We propose a number of areas where more research is required, particularly the development of risk tools clinicians can utilise in practice

High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in Victims with Major Depressive Disorder

We carried out whole-exome ultra-high throughput sequencing in brain samples of suicide victims who had suffered from major depressive disorder and control subjects who had died from other causes. This study aimed to reveal the selective accumulation of rare variants in the coding and the UTR sequences within the genes of suicide victims. We also analysed the potential effect of STR and CNV variations, as well as the infection of the brain with neurovirulent viruses in this behavioural disorder. As a result, we have identified several candidate genes, among others three calcium channel genes that may potentially contribute to completed suicide. We also explored the potential implication of the TGF-β signalling pathway in the pathogenesis of suicidal behaviour. To our best knowledge, this is the first study that uses whole-exome sequencing for the investigation of suicide

The Impact of HIV Infection and CD4 Cell Count on the Performance of an Interferon Gamma Release Assay in Patients with Pulmonary Tuberculosis

BACKGROUND:The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance. METHODOLOGY/PRINCIPAL FINDINGS:161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39). CONCLUSIONS/SIGNIFICANCE:Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent

Community-based cross-sectional survey of latent tuberculosis infection in Afar pastoralists, Ethiopia, using QuantiFERON-TB Gold In-Tube and tuberculin skin test

<p>Abstract</p> <p>Background</p> <p>There is little information concerning community-based prevalence of latent tuberculosis infection (LTBI) using T-cell based interferon-γ (IFN-γ) release assays (IGRAs), particularly in TB endemic settings. In this study, the prevalence of LTBI in the Afar pastoral community was assessed using QuantiFERON-TB Gold In-Tube (QFTGIT) and tuberculin skin tests (TST).</p> <p>Methods</p> <p>A community-based cross-sectional survey of LTBI involving 652 apparently healthy adult pastoralists was undertaken in the pastoral community of Amibara District of the Afar Region between April and June 2010.</p> <p>Results</p> <p>The prevalence of LTBI was estimated as 63.7% (363/570) using QFTGIT at the cut-off point recommended by the manufacturer (≥ 0.35 IU/ml IFN-γ), while it was 74.9% (427/570) using a cut-off point ≥ 0.1 IU/ml IFN-γ. The QFTGIT-based prevalence of LTBI was not significantly associated with the gender or age of the study participants. However, the prevalence of LTBI was 31.2% (183/587) using TST at a cut-off point ≥ 10 mm of skin indurations, and it was higher in males than females (36.8% vs. 23.5%, X²= 11.76; p < 0.001). There was poor agreement between the results of the tests (k = 0.098, 95% CI, 0.08 - 0.13). However, there was a positive trend between QFTGIT and TST positivity (X²= 96.76, P < 0.001). Furthermore, individuals with skin indurations ≥ 10 mm were 13.6 times more likely to have positive results using QFTGIT than individuals with skin indurations of 0 mm (adjusted OR = 13.6; 95%CI, 7.5 to 24.7, p < 0.001).</p> <p>Conclusions</p> <p>There is currently no agreed gold standard for diagnosis of LTBI. However, the higher prevalence of LTBI detected using QFTGIT rather than TST suggests that QFTGIT could be used for epidemiological studies concerning LTBI at the community level, even in a population unreactive to TST. Further studies of adults and children will be required to assess the effects of factors such as malnutrition, non-tuberculosis mycobacterial infections, HIV and parasitic infections on the performance of QFTGIT.</p

Imaging evidence and recommendations for traumatic brain injury: advanced neuro- and neurovascular imaging techniques

SUMMARY: Neuroimaging plays a critical role in the evaluation of patients with traumatic brain injury, with NCCT as the first-line of imaging for patients with traumatic brain injury and MR imaging being recommended in specific settings. Advanced neuroimaging techniques, including MR imaging DTI, blood oxygen level-dependent fMRI, MR spectroscopy, perfusion imaging, PET/SPECT, and magnetoencephalography, are of particular interest in identifying further injury in patients with traumatic brain injury when conventional NCCT and MR imaging findings are normal, as well as for prognostication in patients with persistent symptoms. These advanced neuroimaging techniques are currently under investigation in an attempt to optimize them and substantiate their clinical relevance in individual patients. However, the data currently available confine their use to the research arena for group comparisons, and there remains insufficient evidence at the time of this writing to conclude that these advanced techniques can be used for routine clinical use at the individual patient level. TBI imaging is a rapidly evolving field, and a number of the recommendations presented will be updated in the future to reflect the advances in medical knowledge. 2015 by American Journal of Neuroradiology