Miracle-dz/UniFAR-FTUs huggingface dataset:
9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10−29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10−143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10−22) but less strongly, if at all, with ER-negative (ER−) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10−6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783–. ©2012 AACR.
Autism and Fragile X Syndrome

Abstract Autistic spectrum disorders (ASDs) are characterized by impairments in language, social skills, and repetitive behaviors, often accompanied by intellectual disability. Advances in the genetics of ASDs are providing new glimpses into the underlying neurobiological mechanisms disrupted in these conditions. These glimpses on one hand reinforce the idea that synapse development and plasticity are one of the major pathways disrupted in autism, but beyond that are providing fresh molecular support to the idea of mechanistic parallels between idiopathic ASD and specific syndromic neurodevelopmental disorders like fragile X syndrome (FXS). Fragile X syndrome is already recognized as the most common identifiable genetic cause of intellectual disability and ASDs, with many overlapping phenotypic features. Fragile X syndrome is associated with a variety of cognitive, behavioral, physical, and medical problems, which are managed through supportive treatment. Recent major advances in the understanding of the underlying neurobiology in FXS have led to the discovery of agents that rescue phenotypes in the FXS mouse model, and early clinical trials of targeted treatments in humans with FXS. Thus translational strategies in FXS may be poised to serve as models for ASD and other cognitive disorders.
High speed machining induced residual stresses in Grade 5 titanium alloy

The surface and near surface residual stress state induced by machining may have a significant effect on the structural integrity of some important mechanical components. This article describes an experimental investigation of this stress state during high speed machining of Grade 5 titanium alloy (Ti6Al4V). The size and depth of the stress field is evaluated by non-contact probing measurement techniques as a function of cutting speed (70–200 m/min) and depth of cut (0.25–1.0 mm). X-ray diffraction and synchrotron energy dispersive diffraction are used to evaluate the surface (X-ray diffraction) and sub-surface (energy dispersive diffraction) residual stress fields. The results indicate that both techniques may be successfully employed to evaluated machining induced residual stress fields and that the energy dispersive diffraction method is eminently suitable for probe depths up to 100 µm in Grade 5. The results clearly indicated that significant residual stresses are introduced during machining both at conventional and high cutting speeds. The stresses are largely compressive and aligned with the main cutting direction for both rough and finish cuts. The results also show that the residual stress level is a strong function of the cutting speed. The overall stress level effectively becomes more tensile but also decreases with increasing cutting speed.
The value of a multi-specialty service, including genitourinary medicine, dermatology and urology input, in the management of male genital dermatoses

We undertook a retrospective case note review of our monthly multi-specialty penile dermatoses clinic (which includes clinicians from Genitourinary medicine, Dermatology and Urology), to examine conditions presenting to the service, and compare clinical management and outcomes with other similar services in the UK. Over the 3-year study period, 226 patients were reviewed over 240 individual episodes. Lichenoid conditions were the most common category of genital pathologies seen (n = 60, 24%), but non-specific balanitis was the most common individual diagnosis (n = 55, 22%). Other common conditions seen included eczema and psoriasis (n = 28, 11%), Zoon/plasma cell balanitis (n = 26, 10%), malignancy/pre-malignant change (n = 25, 10%) and infective conditions (n = 24, 9%). The clinic had a biopsy rate of 10%; the most common indication was for confirmation of a clinical suspicion of malignancy/pre-malignancy. There was a high clinical-to-histological correlation in the biopsies of 79%. The most common treatment prescribed was topical corticosteroids and the clinic had a high discharge rate of 93%, the majority of patients discharged back to General Practice.
The International SAT Solver Competitions

The International SAT Solver Competition is today an established series of competitive events aiming at objectively evaluating the progress in state-of-the-art procedures for solving Boolean satisfiability (SAT) instances. Over the years, the competitions have significantly contributed to the fast progress in SAT solver technology that has made SAT a practical success story of computer science. This short article provides an overview of the SAT solver competitions.
Family History and the Risk of Sudden Cardiac Death as a Manifestation of an Acute Coronary Event

Background— Observational studies have suggested that a parental history of sudden death increases one’s risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event. Methods and Results— A retrospective case-control study included (1) consecutive victims of SCD (n=138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects (n=470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group. The incidence of SCD in the 1223 first-degree relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2, P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001). The history of SCD in 2 or more first-degree relatives was also higher (10.9%) among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8, P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family history of AMI did not differ between the SCD and AMI groups. Male gender and current smoking were the only coronary risk factors that were more prevalent among SCD victims than among AMI survivors (P<0.001 for both). Conclusions— Subjects with a family history of SCD have an increased risk of dying suddenly during an acute coronary event.
Tradeoffs for nearest neighbors on the sphere

We consider tradeoffs between the query and update complexities for the (approximate) nearest neighbor problem on the sphere, extending the recent spherical filters to sparse regimes and generalizing the scheme and analysis to account for different tradeoffs. In a nutshell, for the sparse regime the tradeoff between the query complexity $n^{\rho_q}$ and update complexity $n^{\rho_u}$ for data sets of size $n$ is given by the following equation in terms of the approximation factor $c$ and the exponents $\rho_q$ and $\rho_u$: $$c^2\sqrt{\rho_q}+(c^2-1)\sqrt{\rho_u}=\sqrt{2c^2-1}. $$ For small $c=1+\epsilon$, minimizing the time for updates leads to a linear space complexity at the cost of a query time complexity $n^{1-4\epsilon^2}$. Balancing the query and update costs leads to optimal complexities $n^{1/(2c^2-1)}$, matching bounds from [Andoni-Razenshteyn, 2015] and [Dubiner, IEEE-TIT'10] and matching the asymptotic complexities of [Andoni-Razenshteyn, STOC'15] and [Andoni-Indyk-Laarhoven-Razenshteyn-Schmidt, NIPS'15]. A subpolynomial query time complexity $n^{o(1)}$ can be achieved at the cost of a space complexity of the order $n^{1/(4\epsilon^2)}$, matching the bound $n^{\Omega(1/\epsilon^2)}$ of [Andoni-Indyk-Patrascu, FOCS'06] and [Panigrahy-Talwar-Wieder, FOCS'10] and improving upon results of [Indyk-Motwani, STOC'98] and [Kushilevitz-Ostrovsky-Rabani, STOC'98]. For large $c$, minimizing the update complexity results in a query complexity of $n^{2/c^2+O(1/c^4)}$, improving upon the related exponent for large $c$ of [Kapralov, PODS'15] by a factor $2$, and matching the bound $n^{\Omega(1/c^2)}$ of [Panigrahy-Talwar-Wieder, FOCS'08]. Balancing the costs leads to optimal complexities $n^{1/(2c^2-1)}$, while a minimum query time complexity can be achieved with update complexity $n^{2/c^2+O(1/c^4)}$, improving upon the previous best exponents of Kapralov by a factor $2$.
Landscape-Scale Disturbances Modified Bird Community Dynamics in Successional Forest Environment

Ecosystem-based forest management strives to develop silvicultural practices that best emulate natural disturbances such as wildfire to conserve biodiversity representative of natural forest ecosystems. Yet, current logging practices alter forest structure and reduce the proportion of old-growth forest and, consequently, can exert long-term effects on the dynamics of forest biota. The stand- and landscape-scale factors driving bird community dynamics in post-disturbance environment remain poorly understood. In this study, we examined bird community dynamics along successional gradients in boreal ecosystems originating from fire and logging in landscapes dominated by old-growth forest. We tested if bird species richness and community compositions in clear-cutting stands became comparable to those in natural stands after 70 years, and identified the relative contributions of stand- and landscape-scale forest attributes in bird community dynamics. Based on records of bird occurrences at 185 field sites in natural and clearcutting stands, we demonstrate that (1) both forest structures and bird communities underwent evident changes along successional gradients in post-clearcutting environment; (2) bird species richness and community composition in 60- to 70-years-old clearcutting stands still differed from those in 50- to 79-years-old natural stands, in spite of the fact that most forest attributes of clearcutting stands became comparable to those of natural stands after 40 years; and (3) landscape disturbances contributed more than stand characteristics in explaining the lack of convergence of mature forest species, residents, and short-distance migrants in post-clearcutting environment. Our study points out that more regards should be paid to improve the landscape configuration of the managed forests, and implies that old-growth forest retention within logged areas, combined with selection cutting and prolonged logging rotations, can better emulate fire and alleviate forest harvesting effects on bird community assemblages typical of natural boreal ecosystem.
Oral Immunoglobulin Levels are Not a Good Surrogate for Cervical Immunoglobulin Levels

Background: We sought to determine whether oral secretions could be used as a surrogate for cervical secretions for monitoring cervical immunoglobulin (Ig) levels. To do so, we examined (1) whether oral IgG and IgA levels correlated with those observed at the cervix, and (2) whether time of menstrual cycle and other factors previously reported to influence cervical Ig levels were associated with oral IgG and IgA levels. Methods: We obtained oral samples from a group of 85 Costa Rican woman 25–35 years of age measured at three time points during one menstrual cycle. Total IgG and IgA levels were measured by ELISA. Generalized estimating equations methods that account for repeated measures were used to evaluate the association between oral and cervical Ig levels and to evaluate the association between various covariates and oral IgA and IgG levels. Results: We did not observe an association between oral and cervical IgG [linear regression coefficient (LRC) 0.01; 95% CI, −0.05 to 0.07] and IgA levels (LRC 0.02; 95% CI, −0.04 to 0.08). Oral IgG and IgA levels were not influenced by phase of menstrual cycle, in contrast to what has previously been observed for cervical Ig levels. Conclusion: Our data suggest that oral IgG and IgA measures are not a good surrogate for cervical IgG and IgA levels. Future studies should examine whether antigen-specific antibody responses induced by vaccination correlate across mucosal sites.
Usefulness of exhaled nitric oxide and sputum eosinophils in the long-term control of eosinophilic asthma.

BACKGROUND The aim of the present study was to treat unstable asthma according to exhaled nitric oxide (eNO) and induced-sputum eosinophils (sEos) levels to assess if this strategy is better than the conventional approach based on symptoms and function to achieve asthma control. METHODS Fourteen patients with mild-to-moderate persistent asthma (6 men, 8 women) were recruited. During the recruitment visit, the patients, previously treated for asthma following Global Initiative for Asthma recommendations, underwent clinical evaluation and pulmonary function tests (PFTs). Then, after 4 weeks of washout from inhaled antiinflammatory treatment, the patients underwent a basal visit performing PFTs, challenge test to methacholine, and determination of eNO and sEos counts. These procedures were repeated after 3, 6, and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values. RESULTS At the end of the study, a significant decrease in eNO and sEos was observed (57.2 +/- 32.8 parts per billion [ppb] vs 22.1 +/- 10.8 ppb, p < 0.01; and 27.1 +/- 27.1% vs 3.7 +/- 3.5%, p < 0.01, respectively). A close correlation (r2 = 0.41, p < 0.01) between the percentage change of eNO and sEos was observed only after 6 months. Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated. CONCLUSIONS Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease. The eNO decrease reflects adequately the reduction of sEos only after 6 months.
Understanding the experience of caring for children with haemophilia: cross‐sectional study of caregivers in the United States

Congenital haemophilia is an inherited bleeding disorder typically diagnosed at birth or shortly thereafter. Haemophilia imposes a significant burden on patients and their caregivers. The aim of the study was to quantify the overall burden of haemophilia on caregivers in the USA using a novel disease‐specific questionnaire and the previously validated CarerQol. Targeted literature review and a previous survey conducted by the authors was used to develop an online questionnaire with six burden domains of interest to caregivers (emotional stress, financial, sacrifice, medical management, child's pain and transportation) and several visual analogue scales (VAS). Content validity of the questionnaire was confirmed by three haemophilia caregivers. The study sample consisted of caregivers of children with haemophilia identified via a previously developed opt‐in research database. Descriptive statistics were employed for demographic and clinical characteristics; a generalized linear model (GLM) was used to identify factors influencing caregiver burden. A total of 310 caregivers completed the survey (45.5% response rate). Most of the participating caregivers were mothers of a child with haemophilia (88%), between 35 and 44 years of age (48%), and with a college education or a postgraduate degree (63%). ‘Child's pain’ was identified as the most burdensome domain to caregivers (median score = 3.50 out of 5), followed by ‘emotional stress’ (2.67), ‘financial’ (2.40), ‘transportation’ (2.33), ‘sacrifice’ (2.17) and ‘medical management’ (2.00) domains. Although higher income exhibited a protective effect, episodes of bleeds, current presence of an inhibitor and lower caregiver productivity in the past month negatively affected caregiver burden per GLM results. Training and educational programs should potentially be developed to address caregiver burden.
Scalable collaborative filtering using cluster-based smoothing

Memory-based approaches for collaborative filtering identify the similarity between two users by comparing their ratings on a set of items. In the past, the memory-based approach has been shown to suffer from two fundamental problems: data sparsity and difficulty in scalability. Alternatively, the model-based approach has been proposed to alleviate these problems, but this approach tends to limit the range of users. In this paper, we present a novel approach that combines the advantages of these two approaches by introducing a smoothing-based method. In our approach, clusters generated from the training data provide the basis for data smoothing and neighborhood selection. As a result, we provide higher accuracy as well as increased efficiency in recommendations. Empirical studies on two datasets (EachMovie and MovieLens) show that our new proposed approach consistently outperforms other state-of-art collaborative filtering algorithms.
The effect of tRNA levels on decoding times of mRNA codons

The possible effect of transfer ribonucleic acid (tRNA) concentrations on codons decoding time is a fundamental biomedical research question; however, due to a large number of variables affecting this process and the non-direct relation between them, a conclusive answer to this question has eluded so far researchers in the field. In this study, we perform a novel analysis of the ribosome profiling data of four organisms which enables ranking the decoding times of different codons while filtering translational phenomena such as experimental biases, extreme ribosomal pauses and ribosome traffic jams. Based on this filtering, we show for the first time that there is a significant correlation between tRNA concentrations and the codons estimated decoding time both in prokaryotes and in eukaryotes in natural conditions (−0.38 to −0.66, all P values <0.006); in addition, we show that when considering tRNA concentrations, codons decoding times are not correlated with aminoacyl-tRNA levels. The reported results support the conjecture that translation efficiency is directly influenced by the tRNA levels in the cell. Thus, they should help to understand the evolution of synonymous aspects of coding sequences via the adaptation of their codons to the tRNA pool.
Aging and spectral analysis of EEG in normal subjects: a link to memory and CSF AChE

We studied the effect of aging on EEG spectra recorded from T5–O1 (T6‐O2) derivation. The aging series composed of 52 normal individuals aged 20 to 91 years. Seventy‐nine per cent of visual and 81% of quantitative EEGs were considered normal. The absolute amplitude of delta and theta bands and absolute power of delta band were lower for the oldest group (aged 60 and over) than for the youngest group (aged 20–39 years). Age was inversely related to the amount of delta and theta indicating that the amount of slow activity in quantitative EEG does not increase with age in the context of good health status. Women had more beta activity compared with men. In addition, the amount of beta and alpha bands showed tendency for a reduction with age. Fifteen subjects aged 50 years or older participated in a 2‐year follow‐up including EEG and neuropsychological evaluation. Seven of them deteriorated in learning ability and showed increase in delta activity. In the oldest age group, delta amplitude was positively correlated with intrusion errors in the list learning test and inversely related to acetylcholinesterase activity of the CSF. Thus, a link between the cholinergic system, EEG slowing and memory problems in old age is suggested.
Robust adaptive beamforming using worst-case performance optimization via Second-Order Cone programming

If the desired signal is present in training snapshots, the adaptive array performance is known to be quite sensitive even to slight mismatches between the presumed and actual signal steering vectors. Such mismatches can occur as a result of environmental nonstationarities, look direction errors, imperfect array calibration or distorted antenna shape, as well as distortions caused by medium inhomogeneities, near-far mismatch, source spreading, and local scattering. The similar type of performance degradation can occur when the signal steering vector is known exactly but the training sample size is small. In this paper, we develop a new approach to robust adaptive beamforming in the presence of an arbitrary unknown signal steering vector mismatch. Our approach is based on the optimization of worst-case performance using Second-Order Cone (SOC) programming. The adaptive beamformer proposed is shown to have a substantially improved robustness as compared to existing algorithms and enjoy simple implementation.
Integrated Block Sharing: A Win-Win Strategy for Hospitals and Surgeons

We consider the problem of balancing two competing objectives in the pursuit of efficient management of operating rooms in a hospital: providing surgeons with predictable, reliable access to the operating room and maintaining high utilization of capacity. The common solution to the first problem (in practice) is to grant exclusive “block time,” in which a portion of the week in an operating room is designated to a particular surgeon, barring other surgeons from using this room/time. As a major improvement over this existing approach, we model the possibility of “shared” block time, which need only satisfy capacity constraints in expectation. We reduce the computational difficulty of the resulting NP-hard block-scheduling problem by implementing a column-generation approach and demonstrate the efficacy of this technique using simulation, calibrated to a real hospital's historical data and objectives.Our simulations illustrate substantial benefits to hospitals under a variety of circumstances and demonstrate the advantages of our new approach relative to a benchmark method taken from the recent literature.