The 100 000 Genomes Project: What it means for paediatrics

The 100 000 Genomes Project is a unique, national programme combining research and transformation of clinical care, by undertaking whole genome sequencing (WGS) in patients with rare diseases and cancer. Made possible by technological advances in next-generation sequencing1 and falling costs, this project aims to find the genes which cause a patient's rare disease and identify genetic changes which occur in the tumour of a child or adult with cancer, to understand the mechanism of disease and develop therapies to personalise treatment. Patients are recruited through the National Health Service (NHS) and their medical course is tracked for life through their NHS number with results fed back through routine NHS services. It will also lay the foundations for a new ‘genomic medicine’ service for the NHS.2 The project is coordinated by Genomics England, with participants enrolled through one of 13 NHS Genomic Medicine Centres (figure 1), covering all of England. Unlike genome projects in other countries3 that have yielded information on variants associated with common diseases and ancestry, the scale of the 100 000 Genomes Project is much greater. The ability to track long-term outcomes through the patients' NHS number provides a unique opportunity to link genomic and phenotypic data to hospital admissions (via hospital episode statistics) as well as lifelong response to interventions and treatments

Signal Processing Methods for Removing the Effects of Whole Body Vibration upon Speech

Humans may be exposed to whole-body vibration in environments where clear speech communications are crucial, particularly during the launch phases of space flight and in high-performance aircraft. Prior research has shown that high levels of vibration cause a decrease in speech intelligibility. However, the effects of whole-body vibration upon speech are not well understood, and no attempt has been made to restore speech distorted by whole-body vibration. In this paper, a model for speech under whole-body vibration is proposed and a method to remove its effect is described. The method described reduces the perceptual effects of vibration, yields higher ASR accuracy scores, and may significantly improve intelligibility. Possible applications include incorporation within communication systems to improve radio-communication systems in environments such a spaceflight, aviation, or off-road vehicle operations

On the probability of occurrence of rogue waves

A number of extreme and rogue wave studies have been conducted theoretically, numerically, experimentally and based on field data in the last years, which have significantly advanced our knowledge of ocean waves. So far, however, consensus on the probability of occurrence of rogue waves has not been achieved. The present investigation is addressing this topic from the perspective of design needs. Probability of occurrence of extreme and rogue wave crests in deep water is here discussed based on higher order time simulations, experiments and hindcast data. Focus is given to occurrence of rogue waves in high sea states

Gentamicin, genetic variation and deafness in preterm children.

Hearing loss in children born before 32 weeks of gestation is more prevalent than in full term infants. Aminoglycoside antibiotics are routinely used to treat bacterial infections in babies on neonatal intensive care units. However, this type of medication can have harmful effects on the auditory system. In order to avoid this blood levels should be maintained in the therapeutic range. However in individuals with a mitochondrial genetic variant (m.1555A > G), permanent hearing loss can occur even when drug levels are within normal limits. The aim of the study is to investigate the burden that the m.1555A > G mutation represents to deafness in very preterm infants

Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in pendred syndrome/enlarged vestibular aqueducts

Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a condition known as non-syndromic EVA. A significant number of patients with Pendred syndrome and non-syndromic EVA show only one mutation in SLC26A4. Two genes, KCNJ10, encoding an inwardly rectifying potassium channel and FOXI1, a transcriptional factor gene, are thought to play a role in the disease phenotypes

The North Sea Andrea storm and numerical simulations

A coupling of a spectral wave model with a nonlinear phase-resolving model is used to reconstruct the evolution of wave statistics during a storm crossing the North Sea on 8–9 November 2007. During this storm a rogue wave (named the Andrea wave) was recorded at the Ekofisk field. The wave has characteristics comparable to the well-known New Year wave measured by Statoil at the Draupner platform 1 January 1995. Hindcast data of the storm at the nearest grid point to the Ekofisk field are here applied as input to calculate the evolution of random realizations of the sea surface and its statistical properties. Numerical simulations are carried out using the Euler equations with a higher-order spectral method (HOSM). Results are compared with some characteristics of the Andrea wave record measured by the down-looking lasers at Ekofisk

Moving from a Product-Based Economy to a Service-Based Economy for a More Sustainable Future

Traditionally, economic growth and prosperity have been linked with the availability, production and distribution of tangible goods as well as the ability of consumers to acquire such goods. Early evidence regarding this connection dates back to Adam Smith's Wealth of Nations (1776), in which any activity not resulting in the production of a tangible good is characterized as unproductive of any value." Since then, this coupling of economic value and material production has been prevalent in both developed and developing economies throughout the world. One unintended consequence of this coupling has been the exponential increase in the amount of solid waste being generated. The reason is that any production and consumption of material goods eventually generates the equivalent amount of (or even more) waste. Exacerbating this problem is the fact that, with today's manufacturing and supply chain management technologies, it has become cheaper to dispose and replace most products rather than to repair and reuse them. This has given rise to what some call a disposable society." To put things in perspective: In 2012 households in the U.K. generated approximately 22 thousand tons of waste, which amounted to 411 kg of waste generated per person (Department for Environment, Food & Rural Affairs, 2015). During the same time period, households in the U.S. generated 251 million tons of waste, which is equivalent to a person generating approximately 2 kg of waste every day (U.S. Environmental Protection Agency, 2012). Out of these 251 million tons of total waste generated, approximately 20% of the discarded items were categorized as durable goods. The disposal of durable goods is particularly worrisome because they are typically produced using material from non- renewable resources such as iron, minerals, and petroleum-based raw materials

Ecological Management of the Alfalfa Leafcutter Bee, Megachile pacifica (Panzer), with Emphasis on Diapause Induction

The effects of photoperiod and temperature on diapause induction in the alfalfa leafcutter bee, Megachile pacifica (Panzer) (=M. rotundata Auct.), were studied during the summers of 1972, 1973 and 1974, The influence of photoperiod and temperature on mortality, rate of development and incidence of diapause was measured during the developmental stages of this insect. The aim of this research was to assess the potential for manipulation of the number of generations of this bee per season so as to develop a practical and ecologically-sound method of management, Eggs, larvae, pupae and adults of M. pacifica were subjected to regimens of temperatures of 5, 10, 14, 16.5, 20, 21, 25, 26.5 and 30°c and photoperiods of 0, 8 and 16 hours of light, Experiments conducted during 1972 and 1973 involved treating eggs and larvae directly to deter-mine whether diapause was induced in the immature stages, No difference was found between the test and control groups, Experiments of 1973 and 1974 involving treatment of either pupae or adults were designed to determine if inducement of diapause was maternal, Treated adults were released, their progeny were collected and reared to check for percent pupation. These experiments on the adults failed to show any difference between the experimental and control groups in percentage of diapause. Treatment of the pupal stage was conducted in 1974 by subjecting stages from the dark pupa to pre-emerged adult to a temperature of 10° C for 3 hours daily for 8 consecutive days. This low-temperature treatment proved to be most effective in inducing diapause, resulting in 96 percent diapause as compared to 60 percent for the control group. The findings indicate that diapause in M. pacifica is maternally induced and that the possibility of developing a practical method for producing either univoltine or bivoltine generations per season is promising. Recommendations are given for better management of M. pacifica

Properties of the Galactic population of cataclysmic variables in hard X-rays

We measure the spatial distribution and hard X-ray luminosity function of cataclysmic variables (CVs) using the INTEGRAL all-sky survey in the 17-60 keV energy band. The vast majority of the INTEGRAL detected CVs are intermediate polars with luminosities in the range 10^{32}-10^{34} erg/sec. The scale height of the Galactic disk population of CVs is found to be 130{+90}{-50} pc. The CV luminosity function measured with INTEGRAL in hard X-rays is compatible with that previously determined at lower energies (3--20 keV) using a largely independent sample of sources detected by RXTE (located at |b|>10deg as opposed to the INTEGRAL sample, strongly concentrated to the Galactic plane). The cumulative 17-60 keV luminosity density of CVs per unit stellar mass is found to be (1.3+/-0.3)x10^{27} erg/sec/Msun and is thus comparable to that of low-mass X-ray binaries in this energy band. Therefore, faint but numerous CVs are expected to provide an important contribution to the cumulative hard X-ray emission of galaxies.Comment: 8 pages, 8 figures. Submitted to A&

A survey for near-infrared H2 emission in Herbig Ae/Be stars: emission from the outer disks of HD 97048 and HD 100546

We report on a sensitive search for H2 1-0 S(1), 1-0 S(0) and 2-1 S(1) ro-vibrational emission at 2.12, 2.22 and 2.25 micron in a sample of 15 Herbig Ae/Be stars employing CRIRES, the ESO-VLT near-infrared high-resolution spectrograph, at R~90,000. We detect the H2 1-0 S(1) line toward HD 100546 and HD 97048. In the other 13 targets, the line is not detected. The H2 1-0 S(0) and 2-1 S(1) lines are undetected in all sources. This is the first detection of near-IR H2 emission in HD 100546. The H2 1-0 S(1) lines observed in HD 100546 and HD 97048 are observed at a velocity consistent with the rest velocity of both stars, suggesting that they are produced in the circumstellar disk. In HD 97048, the emission is spatially resolved and it is observed to extend at least up to 200 AU. We report an increase of one order of magnitude in the H2 1-0 S(1) line flux with respect to previous measurements taken in 2003 for this star, which suggests line variability. In HD 100546 the emission is tentatively spatially resolved and may extend at least up to 50 AU. Modeling of the H2 1-0 S(1) line profiles and their spatial extent with flat keplerian disks shows that most of the emission is produced at a radius >5 AU. Upper limits to the H2 1-0 S(0)/ 1-0 S(1) and H2 2-1 S(1)/1-0 S(1) line ratios in HD 97048 are consistent with H2 gas at T>2000 K and suggest that the emission observed may be produced by X-ray excitation. The upper limits for the line ratios for HD 100546 are inconclusive. Because the H2 emission is located at large radii, for both sources a thermal emission scenario (i.e., gas heated by collisions with dust) is implausible. We argue that the observation of H2 emission at large radii may be indicative of an extended disk atmosphere at radii >5 AU. This may be explained by a hydrostatic disk in which gas and dust are thermally decoupled or by a disk wind caused by photoevaporation.Comment: Accepted by A&A. 16 pages, 7 figure