Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data ...recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.
Spondyloepimetaphyseal dysplasia with severe short stature, RPL13-related (SEMD-RPL13), MIM#618728), is a rare autosomal dominant disorder characterized by short stature and skeletal changes such as ...mild spondylar and epimetaphyseal dysplasia affecting primarily the lower limbs. The genetic cause was first reported in 2019 by Le Caignec et al., and six disease-causing variants in the gene coding for a ribosomal protein, RPL13 (NM_000977.3) have been identified to date. This study presents clinical and radiographic data from 12 affected individuals aged 2-64 years from seven unrelated families, showing highly variable manifestations. The affected individuals showed a range from mild to severe short stature, retaining the same radiographic pattern of spondylar- and epi-metaphyseal dysplasia, but with varying severity of the hip and knee deformities. Two new missense variants, c.548 G>A, p.(Arg183His) and c.569 G>T, p.(Arg190Leu), and a previously known splice variant c.477+1G>A were identified, confirming mutational clustering in a highly specific RNA binding motif. Structural analysis and interpretation of the variants' impact on the protein suggests that disruption of extra-ribosomal functions of the protein through binding of mRNA may play a role in the skeletal phenotype of SEMD-RPL13. In addition, we present gonadal and somatic mosaicism for the condition.
Urothelial bladder cancer (UBC) is the 5.sup.th most common cancer in Western societies. The most common symptom of UBC is haematuria. Cystoscopy the gold standard for UBC detection, allows direct ...observation of the bladder, but is expensive, invasive, and uncomfortable. This study examines whether an alternative new urine-based diagnostic test, the DCRSHP, is cost-effective as a triage diagnostic tool compared to flexible cystoscopy in the diagnosis of UBC in haematuria patients. A model-based cost-utility analysis using cost per quality adjusted life year and life year gained, parameterised with secondary data sources. If the DCRSHP is targeted at haematuria patients at lower risk of having bladder cancer e.g. younger patients, non-smokers, then it can be priced as high as £620, and be both effective and cost-effective. Sensitivity analysis found that DCRSHP is approximately 80% likely to be cost-effective across all willingness to pay values (for a QALY) and prevalence estimates. This analysis shows the potential for a non-invasive test to be added to the diagnostic pathway for haematuria patients suspected of having UBC. If the DCRSHP is applied targeting haematuria patients at low risk of UBC, then it has the potential to be both effective and cost-effective.
Focal dermal hypoplasia (FDH) is an X-linked dominant disorder caused by mutations in the gene PORCN, which encodes a protein required for the secretion and signaling of Wnt proteins. While deletions ...are responsible for a small percentage of FDH-causing mutations, the vast majority of mutations are single-nucleotide substitutions or small deletions or insertions that can be identified by sequence analysis. In 2007, we implemented a PORCN gene sequencing test for individuals with a clinical diagnosis of FDH. To date, we have detected 12 novel PORCN mutations and 6 previously reported mutations in 53 such unrelated patients. The pathogenic PORCN mutations included nine nonsense mutations, three missense mutations, one small deletion, two small duplications, and three splice-site mutations. Of these mutations, two were found in affected men and were mosaic; one of these was found in three other affected women. The remaining 16 mutations were found only in women. All the mutations detected in women were presumed heterozygous. In addition to the disease-causing mutations, eight nucleotide variants of unknown significance were identified. Further characterization of these variants suggests that four of them are pathogenic mutations. These findings add to the heterogeneity of mutations in the PORCN gene that cause FDH.
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