A new accuracy measure based on bounded relative error for time series forecasting

Many accuracy measures have been proposed in the past for time series forecasting comparisons. However, many of these measures suffer from one or more issues such as poor resistance to outliers and scale dependence. In this paper, while summarising commonly used accuracy measures, a special review is made on the symmetric mean absolute percentage error. Moreover, a new accuracy measure called the Unscaled Mean Bounded Relative Absolute Error (UMBRAE), which combines the best features of various alternative measures, is proposed to address the common issues of existing measures. A comparative evaluation on the proposed and related measures has been made with both synthetic and real-world data. The results indicate that the proposed measure, with user selectable benchmark, performs as well as or better than other measures on selected criteria. Though it has been commonly accepted that there is no single best accuracy measure, we suggest that UMBRAE could be a good choice to evaluate forecasting methods, especially for cases where measures based on geometric mean of relative errors, such as the geometric mean relative absolute error, are preferred

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

The effect of pond dyes on oviposition and survival in wild UK Culex mosquitoes

British Culex pipiens complex [Culex pipiens sensu lato) mosquito distribution, abundance, and potential for disease transmission are intimately linked to their environment. Pond and lake dyes that block light to restrict algal photosynthesis are a relatively new product assumed to be an environmentally friendly since they are based on food dyes. Their use in urban garden ponds raises questions linked to mosquito oviposition, since coloured water can be an attractant. Culex (mostly pipiens) is commonly found in UK gardens and is a potential vector of viruses including the West Nile Virus (WNV). Any factors that significantly change the distribution and population of Cx pipiens could impact future risks of disease transmission. A gravid trap was used to catch female Cx pipiens mosquitoes for use in oviposition choice tests in laboratory and semi-field conditions. Two types of pond dye, blue and shadow (which looks slightly red), were tested for their impact on oviposition and survival of wild caught Cx pipiens. There were no significant differences in the number of egg batches laid when gravid mosquitoes were given a choice between either blue dye and clear water or shadow dye and clear water indicating that these dyes are not attractants. Larvae hatched from egg batches laid by wild-caught gravid females were used to measure survival to adulthood with or without dye, , in a habitat controlled to prevent further colonisation. The experiment was run twice, once in the summer and again in the autumn, whereas the dyes had no impact on emergence in the summer, there were highly significant reductions in emergence of adults in both dye treated habitats in the autumn. Containers with or without shadow dye were placed outside to colonise naturally and were sampled weekly for larvae and pupae over a 6 month period through summer and autumn. There was a significant negative effect of shadow dye on pupal abundance in a three week period over the summer, but otherwise there was no effect. It is likely that population abundance and food was a more powerful factor for mosquito survival than the dye

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.

Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016

H-ATLAS/GAMA: The nature and characteristics of optically red galaxies detected at submillimetre wavelengths

We combine Herschel/SPIRE sub-millimeter (submm) observations with existing multi-wavelength data to investigate the characteristics of low redshift, optically red galaxies detected in submm bands. We select a sample of galaxies in the redshift range 0.01$\leq$z$\leq$0.2, having >5$\sigma$ detections in the SPIRE 250 micron submm waveband. Sources are then divided into two sub-samples of $red$ and $blue$ galaxies, based on their UV-optical colours. Galaxies in the $red$ sample account for $\approx$4.2 per cent of the total number of sources with stellar masses M$_{*}\gtrsim$10$^{10}$ Solar-mass. Following visual classification of the $red$ galaxies, we find that $\gtrsim$30 per cent of them are early-type galaxies and $\gtrsim$40 per cent are spirals. The colour of the $red$-spiral galaxies could be the result of their highly inclined orientation and/or a strong contribution of the old stellar population. It is found that irrespective of their morphological types, $red$ and $blue$ sources occupy environments with more or less similar densities (i.e., the $\Sigma_5$ parameter). From the analysis of the spectral energy distributions (SEDs) of galaxies in our samples based on MAGPHYS, we find that galaxies in the $red$ sample (of any morphological type) have dust masses similar to those in the $blue$ sample (i.e. normal spiral/star-forming systems). However, in comparison to the $red$-spirals and in particular $blue$ systems, $red$-ellipticals have lower mean dust-to-stellar mass ratios. Besides galaxies in the $red$-elliptical sample have much lower mean star-formation/specific-star-formation rates in contrast to their counterparts in the $blue$ sample. Our results support a scenario where dust in early-type systems is likely to be of an external origin

Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity

Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs’ biological targets. In this study, we have used data mining techniques and mutual information statistical approaches to find associations between reported adverse events collected from the FDA Adverse Event Reporting System and assay outcomes from ToxCast, with the aim to generate mechanistic hypotheses related to structural cardiotoxicity (morphological damage to cardiomyocytes and/or loss of viability). Our workflow identified 22 adverse event-assay outcome associations. From these associations, 10 implicated targets could be substantiated with evidence from previous studies reported in the literature. For two of the identified targets, we also describe a more detailed mechanism, forming putative adverse outcome pathways associated with structural cardiotoxicity. Our study also highlights the difficulties deriving these type of associations from the very limited amount of data available

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa