Simultaneous interval regression for K-nearest neighbor

International audienceIn some regression problems, it may be more reasonable to predict intervals rather than precise values. We are interested in finding intervals which simultaneously for all input instances x ∈X contain a β proportion of the response values. We name this problem simultaneous interval regression. This is similar to simultaneous tolerance intervals for regression with a high confidence level γ ≈ 1 and several authors have already treated this problem for linear regression. Such intervals could be seen as a form of confidence envelop for the prediction variable given any value of predictor variables in their domain. Tolerance intervals and simultaneous tolerance intervals have not yet been treated for the K-nearest neighbor (KNN) regression method. The goal of this paper is to consider the simultaneous interval regression problem for KNN and this is done without the homoscedasticity assumption. In this scope, we propose a new interval regression method based on KNN which takes advantage of tolerance intervals in order to choose, for each instance, the value of the hyper-parameter K which will be a good trade-off between the precision and the uncertainty due to the limited sample size of the neighborhood around each instance. In the experiment part, our proposed interval construction method is compared with a more conventional interval approximation method on six benchmark regression data sets

miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation

B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development

Piecewise Approximate Bayesian Computation: fast inference for discretely observed Markov models using a factorised posterior distribution

Many modern statistical applications involve inference for complicated stochastic models for which the likelihood function is difficult or even impossible to calculate, and hence conventional likelihood-based inferential techniques cannot be used. In such settings, Bayesian inference can be performed using Approximate Bayesian Computation (ABC). However, in spite of many recent developments to ABC methodology, in many applications the computational cost of ABC necessitates the choice of summary statistics and tolerances that can potentially severely bias the estimate of the posterior. We propose a new “piecewise” ABC approach suitable for discretely observed Markov models that involves writing the posterior density of the parameters as a product of factors, each a function of only a subset of the data, and then using ABC within each factor. The approach has the advantage of side-stepping the need to choose a summary statistic and it enables a stringent tolerance to be set, making the posterior “less approximate”. We investigate two methods for estimating the posterior density based on ABC samples for each of the factors: the first is to use a Gaussian approximation for each factor, and the second is to use a kernel density estimate. Both methods have their merits. The Gaussian approximation is simple, fast, and probably adequate for many applications. On the other hand, using instead a kernel density estimate has the benefit of consistently estimating the true piecewise ABC posterior as the number of ABC samples tends to infinity. We illustrate the piecewise ABC approach with four examples; in each case, the approach offers fast and accurate inference

BIOLEACHING OF COBALT AND ZINC FROM PYRITE ORE IN RELATION TO CALCITIC GANGUE CONTENT

Bioleaching of a pyrite ore containing high concentrations of cobalt (0.1%) and zinc (0.065%) was affected by small amounts of calcitic gangue (from 0.01 to 1.01%). Results from an air-lift percolator and from Erlenmeyer flask experiments show that a small percentage of calcite raises the pH and arrests the growth of the acidophilic bacterium Thiobacillus ferrooxidans. In percolator experiments, when calcite is completely removed by the continuous addition of small quantities of acid, and the pH of the liquor becomes acid, the micro-organism begins to grow and to bio-oxidize the pyrite ore. The growth of T. ferrooxidans shows different lag phase spans (from 13 to 190 days) depending on carbonate dissolution. The metals Fe, Zn and Co are released into the leaching solution together at different rates after a lag-time which depends on calcite concentrations in pyrite gangue. Metal ratios in the mineral bulk are different from those in the liquor, Zn dissolving 5 times more readily than Co. Bioleaching rates for metal removal from pyrite are higher in percolator (for Fe, from 5 to 15 mg/l/h) than in flask experiments (from 0.5 to 2 mg/l/h), but the lag phases are shorter (from 2 to 65 days). The differences between the two systems are related to calcite dissolution and gypsum precipitation

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3- sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating antidsDNA autoreactivity in patients with severe sporadic SLE

Engaging audiences with difficult pasts: the Voices of ’68 Project at the Ulster Museum, Belfast

Can history museums influence the relationship between divided communities? This paper explores why an initially modest collaboration between the authors and the Ulster Museum on the non‐violent Northern Ireland Civil Rights Movement of 1968/69, eventually had substantial impact beyond the museum’s walls. Having placed the Northern Ireland Civil Rights Movement within the context of both the international protests of 1968 and the specific environment of Northern Ireland, particularly the virtual civil war known as the Troubles, the paper turns to the role of museums in responding to the legacy of this past, and the evolving practice of the Ulster Museum, as background to the project. The latter began as a limited intervention within an existing display, based on oral histories and underpinned by the theory of ‘agonism’, proposing that divided communities must learn to live with difference. It eventually included exhibitions, workshops, school study days, curricular materials and online provision. It has directly influenced the Northern Ireland GCSE History Curriculum and been held up as an example of good practice within the province’s peace process. The paper discusses why the project succeeded – location within a national museum; credibility with protagonists, academics, communities and audiences; starting small; a willingness to take risks and share control; multiple perspectives; and an acceptance that not everyone will be satisfied. With a version of the Voices of 68 exhibition now installed in the Museum’s permanent gallery, the next challenges are longitudinal studies on its impact and assessing the approach’s relevance to other museums working in post‐conflict societies

Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants

Chronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry

Editorial Statement About JCCAP’s 2023 Special Issue on Informant Discrepancies in Youth Mental Health Assessments: Observations, Guidelines, and Future Directions Grounded in 60 Years of Research

Issue 1 of the 2011 Volume of the Journal of Clinical Child and Adolescent Psychology (JCCAP) included a Special Section about the use of multi-informant approaches to measure child and adolescent (i.e., hereafter referred to collectively as “youth”) mental health (De Los Reyes, 2011). Researchers collect reports from multiple informants or sources (e.g., parent and peer, youth and teacher) to estimate a given youth’s mental health. The 2011 JCCAP Special Section focused on the most common outcome of these approaches, namely the significant discrepancies that arise when comparing estimates from any two informant’s reports (i.e., informant discrepancies). These discrepancies appear in assessments conducted across the lifespan (Achenbach, 2020). That said, JCCAP dedicated space to understanding informant discrepancies, because they have been a focus of scholarship in youth mental health for over 60 years (e.g., Achenbach et al., 1987; De Los Reyes & Kazdin, 2005; Glennon & Weisz, 1978; Kazdin et al., 1983; Kraemer et al., 2003; Lapouse & Monk, 1958; Quay et al., 1966; Richters, 1992; Rutter et al., 1970; van der Ende et al., 2012). Thus, we have a thorough understanding of the areas of research for which they reliably appear when clinically assessing youth. For instance, intervention researchers observe informant discrepancies in estimates of intervention effects within randomized controlled trials (e.g., Casey & Berman, 1985; Weisz et al., 2017). Service providers observe informant discrepancies when working with individual clients, most notably when making decisions about treatment planning (e.g., Hawley & Weisz, 2003; Hoffman & Chu, 2015). Scholars in developmental psychopathology observe these discrepancies when seeking to understand risk and protective factors linked to youth mental health concerns (e.g., Hawker & Boulton, 2000; Hou et al., 2020; Ivanova et al., 2022). Thus, the 2011 JCCAP Special Section posed a question: Might these informant discrepancies contain data relevant to understanding youth mental health? Suppose none of the work in youth mental health is immune from these discrepancies. In that case, the answer to this question strikes at the core of what we produce―from the interventions we develop and implement, to the developmental psychopathology research that informs intervention development