Anogenital distance and penile length in infants with hypospadias or cryptorchidism: comparison with normative data.

BACKGROUND: Anogenital distance (AGD) in animals is a sensitive biomarker of fetal endocrine disruption and the associated testicular dysgenesis syndrome (TDS). However, AGD in human infants with cryptorchidism and hypospadias, which are potential manifestations of TDS during childhood, is not clearly described. OBJECTIVE: Our aim was to compare AGD in boys with cryptorchidism or hypospadias against normative data. METHODS: Boys with isolated cryptorchidism (n = 71, age 13.4 ± 5.8 months) or hypospadias (n = 81, age 11.4 ± 6.2 months) were recruited from a tertiary center for measurement of AGD and penile length; they were compared with 487 healthy full-term boys from a birth cohort by deriving age-specific standard deviation scores (SDS). RESULTS: Boys with cryptorchidism were older (p = 0.048) compared with boys with hypospadias. Boys with hypospadias had shorter mean AGD and penile length SDS than healthy boys (both p < 0.0001). Mean AGD and penile length SDS values in boys with cryptorchidism were longer than mean values in boys with hypospadias (both p < 0.01) and shorter than mean values in healthy boys (both p < 0.0001). Mean penile length SDS decreased as the severity of hypospadias increased (ptrend = 0.078). CONCLUSIONS: In the study population, AGD and penile length were reduced in boys with hypospadias or cryptorchidism relative to normative data derived from a longitudinal birth cohort. The findings support the use of AGD as a quantitative biomarker to examine the prenatal effects of exposure to endocrine disruptors on the development of the male reproductive tract

2021 assessment of the status of the West Coast Demersal Scalefish Resource

A recovery program for the West Coast Demersal Scalefish Resource was introduced between late 2007 and early 2010, based on the maintenance of retained catches of demersal species (overall suite and each indicator species) by both the commercial and recreational sectors below 50% of the catches reported in 2005/06 (original catch recovery benchmarks)

Are Amphipod invaders a threat to the regional biodiversity? Conservation prospects for the Loire River

The impact of invasions on local biodiversity is well established, but their impact on regional biodiversity has so far been only sketchily documented. To address this question, we studied the impact at various observation scales (ranging from the microhabitat to the whole catchment) of successive arrivals of non-native amphipods on the amphipod assemblage of the Loire River basin in France. Amphipod assemblages were studied at 225 sites covering the whole Loire catchment. Non-native species were dominant at all sites in the main channel of the Loire River, but native species were still present at most of the sites. We found that the invaders have failed to colonize most of tributaries of the Loire River. At the regional scale, we found that since the invaders first arrived 25 years ago, the global amphipod diversity has increased by 33% (from 8 to 12 species) due to the arrival of non-native species. We discuss the possibility that the lack of any loss of biodiversity may be directly linked to the presence of refuges at the microhabitat scale in the Loire channel and in the tributaries, which invasive species have been unable to colonize. The restoration of river quality could increase the number of refuges for native species, thus reducing the impact of invader

The Effect of Processing Route on Properties of HfNbTaTiZr High Entropy Alloy

High entropy alloys (HEA) have been one of the most attractive groups of materials for researchers in the last several years. Since HEAs are potential candidates for many (e.g., refractory, cryogenic, medical) applications, their properties are studied intensively. The most frequent method of HEA synthesis is arc or induction melting. Powder metallurgy is a perspective technique of alloy synthesis and therefore in this work the possibilities of synthesis of HfNbTaTiZr HEA from powders were studied. Blended elemental powders were sintered, hot isostatically pressed, and subsequently swaged using a special technique of swaging where the sample is enveloped by a titanium alloy. This method does not result in a full density alloy due to cracking during swaging. Spark plasma sintering (SPS) of mechanically alloyed powders resulted in a fully dense but brittle specimen. The most promising result was obtained by SPS treatment of gas atomized powder with low oxygen content. The microstructure of HfNbTaTiZr specimen prepared this way can be refined by high pressure torsion deformation resulting in a high hardness of 410 HV10 and very fine microstructure with grain size well below 500 nm.11Ysciescopu

Efficacy of early warning signals and spectral periodicity for predicting transitions in bipolar patients:An actigraphy study

Early-warning signals (EWS) have been successfully employed to predict transitions in research fields such as biology, ecology, and psychiatry. The predictive properties of EWS might aid in foreseeing transitions in mood episodes (i.e. recurrent episodes of mania and depression) in bipolar disorder (BD) patients. We analyzed actigraphy data assessed during normal daily life to investigate the feasibility of using EWS to predict mood transitions in bipolar patients. Actigraphy data of 15 patients diagnosed with BD Type I collected continuously for 180 days were used. Our final sample included eight patients that experienced a mood episode, three manic episodes and five depressed episodes. Actigraphy data derived generic EWS (variance and kurtosis) and context-driven EWS (autocorrelation at lag-720) were used to determine if these were associated to upcoming bipolar episodes. Spectral analysis was used to predict changes in the periodicity of the sleep/wake cycle. The study procedures were pre-registered. Results indicated that in seven out of eight patients at least one of the EWS did show a significant change-up till four weeks before episode onset. For the generic EWS the direction of change was always in the expected direction, whereas for the context-driven EWS the observed effect was often in the direction opposite of what was expected. The actigraphy data derived EWS and spectral analysis showed promise for the prediction of upcoming transitions in mood episodes in bipolar patients. Further studies into false positive rates are suggested to improve effectiveness for EWS to identify upcoming bipolar episode onsets

Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genomewide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P = 4.7 x 10(-14), odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P = 6.4 x 10(-10), OR = 3.3, 95% CI = 2.3-4.9). These associations dovetail with the roles of these genes in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG

Assessing the conservation value of waterbodies: the example of the Loire floodplain (France)

In recent decades, two of the main management tools used to stem biodiversity erosion have been biodiversity monitoring and the conservation of natural areas. However, socio-economic pressure means that it is not usually possible to preserve the entire landscape, and so the rational prioritisation of sites has become a crucial issue. In this context, and because floodplains are one of the most threatened ecosystems, we propose a statistical strategy for evaluating conservation value, and used it to prioritise 46 waterbodies in the Loire floodplain (France). We began by determining a synthetic conservation index of fish communities (Q) for each waterbody. This synthetic index includes a conservation status index, an origin index, a rarity index and a richness index. We divided the waterbodies into 6 clusters with distinct structures of the basic indices. One of these clusters, with high Q median value, indicated that 4 waterbodies are important for fish biodiversity conservation. Conversely, two clusters with low Q median values included 11 waterbodies where restoration is called for. The results picked out high connectivity levels and low abundance of aquatic vegetation as the two main environmental characteristics of waterbodies with high conservation value. In addition, assessing the biodiversity and conservation value of territories using our multi-index approach plus an a posteriori hierarchical classification methodology reveals two major interests: (i) a possible geographical extension and (ii) a multi-taxa adaptation

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

Diagnosis and aetiology of congenital muscular dystrophy: we are halfway there

OBJECTIVES: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and Next Generation Sequencing (NGS) technologies. METHODS: 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS. RESULTS: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin α2, α-dystroglycan or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39/123). Of 85 patients presenting in the last 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43/85). The diagnoses within the cohort were heterogeneous. 45/59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11/59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome and two had microdeletions. Within the cohort, five patients had variants in novel (PIGY and GMPPB) or recently published genes (GFPT1 and MICU1) and seven had variants in TTN or RYR1; large genes that are technically difficult to Sanger sequence. INTERPRETATION: These data support NGS as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second-tier investigation. This article is protected by copyright. All rights reserved