Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace (Review)

Background: Fetal vibroacoustic stimulation (VAS) is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesised that the resultant startle reflex in the fetus and subsequent fetal heart rate (FHR) acceleration or transient tachycardia following VAS provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a nonreassuring cardiotocographic (CTG) trace during the first and second stages of labour. Objectives: To evaluate the clinical effectiveness and safety of VAS in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a nonreassuring FHR pattern. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 September 2012) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. Selection criteria: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when VAS was used to evaluate fetal status in the presence of a nonreassuring CTG trace during labour, compared with mock or no stimulation. Data collection and analysis: Two review authors independently sought to assess for inclusion all the potential studies we identified as a result of the search strategy. We planned to resolve any disagreement through discussion or, if required, to consult a third person. Where there was uncertainty about a particular study, we attempted to contact study authors for additional information. However, these attempts were unsuccessful. Main results: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. Authors' conclusions: There are currently no randomised controlled trials that address the safety and efficacy of VAS used to assess fetal well-being in labour in the presence of a nonreassuring CTG trace. Although VAS has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of VAS in the evaluation of fetal well-being in labour in the presence of a nonreassuring CTG trace

The First Detections of the Extragalactic Background Light at 3000, 5500, and 8000A (II): Measurement of Foreground Zodiacal Light

We present a measurement of the absolute surface brightness of the zodiacal light (3900-5100A) toward a fixed extragalactic target at high ecliptic latitude based on moderate resolution (~1.3A per pixel) spectrophotometry obtained with the du Pont 2.5m telescope at Las Campanas Observatory in Chile. This measurement and contemporaneous Hubble Space Telescope data from WFPC2 and FOS comprise a coordinated program to measure the mean flux of the diffuse extragalactic background light (EBL). The zodiacal light at optical wavelengths results from scattering by interplanetary dust, so that the zodiacal light flux toward any extragalactic target varies seasonally with the position of the Earth. This measurement of zodiacal light is therefore relevant to the specific observations (date and target field) under discussion. To obtain this result, we have developed a technique that uses the strength of the zodiacal Fraunhofer lines to identify the absolute flux of the zodiacal light in the multiple-component night sky spectrum. Statistical uncertainties in the result are 0.6% (1 sigma). However, the dominant source of uncertainty is systematic errors, which we estimate to be 1.1% (1 sigma). We discuss the contributions included in this estimate explicitly. The systematic errors in this result contribute 25% in quadrature to the final error in our coordinated EBL measurement, which is presented in the first paper of this series.Comment: Accepted for publication in ApJ, 22 pages using emulateapj.sty, version with higher resolution figures available at http://www.astro.lsa.umich.edu/~rab/publications.html or at http://nedwww.ipac.caltech.edu/level5/Sep01/Bernstein2/frames.htm

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Wear of PEEK-OPTIMA and PEEK-OPTIMA-Wear Performance articulating against highly cross-linked polyethylene

The idea of all polymer artificial joints, particularly for the knee and finger, has been raised several times in the past 20 years. This is partly because of weight but also to reduce stress shielding in the bone when stiffer materials such as metals or ceramics are used. With this in mind, pin-on-plate studies of various polyetheretherketone preparations against highly cross-linked polyethylene were conducted to investigate the possibility of using such a combination in the design of a new generation of artificial joints. PEEK-OPTIMA® (no fibre) against highly cross-linked polyethylene gave very low wear factors of 0.0384 × 10−6 mm3/N m for the polyetheretherketone pins and −0.025 × 10−6 mm3/N m for the highly cross-linked polyethylene plates. The carbon-fibre-reinforced polyetheretherketone (PEEK-OPTIMA®-Wear Performance) also produced very low wear rates in the polyetheretherketone pins but produced very high wear in the highly cross-linked polyethylene, as might have been predicted since the carbon fibres are quite abrasive. When the fibres were predominantly tangential to the sliding plane, the mean wear factor was 0.052 × 10−6 mm3/N m for the pins and 49.3 × 10−6 mm3/N m for the highly cross-linked polyethylene plates; a half of that when the fibres ran axially in the pins (0.138 × 10−6 mm3/N m for the pins and 97.5 × 10−6 mm/ N m for the cross-linked polyethylene plates). PEEK-OPTIMA® against highly cross-linked polyethylene merits further investigation

A practical clinical kinematic model for the upper limbs

A novel clinically practical upper limb model is introduced that has been developed through clinical use in children and adults with neurological conditions to guide surgery to the elbow and wrist. This model has a minimal marker set, minimal virtual markers, and no functional joint centres to minimise the demands on the patient and duration of data collection. The model calculates forearm supination independently from the humerus segment, eliminating any errors introduced by poor modelling of the shoulder joint centre. Supination is calculated by defining the forearm segment twice, from the distal and proximal ends: first, using the ulna and radial wrist markers as a segment defining line and second using the medial and lateral elbow markers as a segment defining line. This is comparable to the clinical measurement of supination utilising a goniometer and enables a reduced marker set, with only the elbow, wrist, and hand markers to be applied when only the wrist and forearm angles are of interest. A sensitivity analysis of the calculated elbow flexion–extension angles to the position of the glenohumeral joint centre is performed on one healthy female subject, aged 20 years, during elbow flexion and a forward reaching task. A comparison of the supination angles calculated utilising the novel technique compared to the rotation between the humeral and forearm segments is also given. All angles are compared to a published kinematic model that follows the recommendations of the International Society of Biomechanics. </jats:p