Correction:A two-arm parallel double-blind randomised controlled pilot trial of the efficacy of Omega-3 polyunsaturated fatty acids for the treatment of women with endometriosis-associated pain (PurFECT1)

[This corrects the article DOI: 10.1371/journal.pone.0227695.]

Early (Days 1–4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy

Acknowledgements S.C.M. was supported by the South-East Scotland Academic Foundation Programme. Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. Funding This project was supported by funding from the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership (grant reference number 14/150/03).Peer reviewedPublisher PD

An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain

Chronic pelvic pain (CPP) affects 5.7-26.6% women worldwide. 55% have no obvious pathology and 40% have associated endometriosis. Neuropathic pain (NeP) is pain arising as a consequence of a lesion/disease affecting the somatosensory system. The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is challenging because there is no gold-standard assessment. Questionnaires have been used in the clinical setting to diagnose NeP in other chronic pain conditions and quantitative sensory testing (QST) has been used in a research setting to identify abnormal sensory function. We aimed to determine if women with chronic pelvic pain (CPP) have a neuropathic pain (NeP) component to their painful symptoms and how this is best assessed. We performed an exploratory prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They underwent a clinician completed questionnaire (DN4) and completed the S-LANSS and PainDETECT™ questionnaires. Additionally QST testing was performed by a clinician. They also completed a patient acceptability questionnaire. Clinical features of NeP were identified by both questionnaires and QST. Of the women who were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and PainDETECT™ respectively. When NeP was identified by questionnaire, the associated laparoscopy findings were similar irrespective of which questionnaire was used. No subject had entirely unchanged QST parameters. There were distinct loss and gain subgroups, as well as mixed alteration in function, but this was not necessarily clinically significant in all patients. 80% of patients were confident that questionnaires could diagnose NeP, and 90% found them easy to complete. Early identification of NeP in women with CPP with a simple questionnaire could facilitate targeted therapy with neuromodulators, which are cheap, readily available, and have good safety profiles. This approach could prevent unnecessary or fertility-compromising surgery and prolonged treatment with hormones

Galaxy Zoo: CANDELS barred discs and bar fractions

The formation of bars in disc galaxies is a tracer of the dynamical maturity of the population. Previous studies have found that the incidence of bars in discs decreases from the local Universe to z ~ 1, and by z > 1 simulations predict that bar features in dynamically mature discs should be extremely rare. Here, we report the discovery of strong barred structures in massive disc galaxies at z ~ 1.5 in deep rest-frame optical images from the Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. From within a sample of 876 disc galaxies identified by visual classification in Galaxy Zoo, we identify 123 barred galaxies. Selecting a subsample within the same region of the evolving galaxy luminosity function (brighter than L*), we find that the bar fraction across the redshift range 0.5 ≤ z ≤ 2 (fbar = 10.7+6.3 -3.5 per cent after correcting for incompleteness) does not significantly evolve.We discuss the implications of this discovery in the context of existing simulations and our current understanding of the way disc galaxies have evolved over the last 11 billion yearsPeer reviewedFinal Accepted Versio

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Combination GnRH antagonists for endometriosis: balancing efficacy with side-effects

Endometriosis is a chronic pain condition affecting 1 in 10 women. There is an unmet need for better medical treatments for endometriosis. We spotlight trials of a single preparation combined HRT-GnRH antagonist (Relugolix) by Giudice et al.,(1) for endometriosis-associated pain