Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but ...not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SN 2014J in M82 is the closest detected Type Ia supernova (SN Ia) in at least 28 yr and perhaps in 410 yr. Despite its small distance of 3.3 Mpc, SN 2014J is surprisingly faint, peaking at ...V = 10.6 mag, and assuming a typical SN Ia luminosity, we infer an observed visual extinction of A
V
= 2.0 ± 0.1 mag. But this picture, with R
V
= 1.6 ± 0.2, is too simple to account for all observations. We combine 10 epochs (spanning a month) of HST/Space Telescope Imaging Spectrograph (STIS) ultraviolet through near-infrared spectroscopy with HST/Wide Field Camera 3 (WFC3), Katzman Automatic Imaging Telescope, and FanCam photometry from the optical to the infrared and nine epochs of high-resolution TRES (Tillinghast Reflection Echelle Spectrograph) spectroscopy to investigate the sources of extinction and reddening for SN 2014J. We argue that the wide range of observed properties for SN 2014J is caused by a combination of dust reddening, likely originating in the interstellar medium of M82, and scattering off circumstellar material. For this model, roughly half of the extinction is caused by reddening from typical dust (E(B − V) = 0.45 mag and R
V
= 2.6) and roughly half by scattering off Large Magellanic Cloud-like dust in the circumstellar environment of SN 2014J.
We present first results of the H2O Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg2 of ...the southern Galactic plane at 12 mm (19.5-27.5 GHz), including spectral line emission from H2O masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and H2O maser emission. We find 540 H2O masers, of which 334 are new detections. The strongest maser is 3933 Jy and the weakest is 0.7 Jy, with 62 masers over 100 Jy. In 14 maser sites, the spread in the velocity of the H2O maser emission exceeds 100 km s−1. In one region, the H2O maser velocities are separated by 351.3 km s−1. The rms noise levels are typically between 1 and 2 Jy, with 95 per cent of the survey under 2 Jy. We estimate completeness limits of 98 per cent at around 8.4 Jy and 50 per cent at around 5.5 Jy. We estimate that there are between 800 and 1500 H2O masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH3 (11,9) and (8,6) emission towards G19.61−0.23 and in the NH3 (3,3) line towards G23.33−0.30.
This book is the long-awaited successor to Owen Phillips's classic textbook, Flow and Reactions in Permeable Rocks, published in 1991. In the intervening 18 years between the two, significant ...advances have been made to our understanding of subterranean flow, especially through the vast amount of research into underground storage of nuclear waste and aquifer pollution. This new book integrates and extends these modern ideas and techniques and applies them to the physics and chemistry of sub-surface flows in water-saturated, sandy and rocky media. It describes essential scientific concepts and tools for hydrologists and public health ecologists concerned with present day flow and transport, and also for geologists who interpret present day patterns of mineralization in terms of fluid flow in the distant past. The book is ideal for graduate students and professionals in hydrology, water resources, and aqueous geochemistry.
We have conducted a Galactic plane survey of methanol masers at 6668 MHz using a seven-beam receiver on the Parkes telescope. Here we present results from the first part, which provides sensitive ...unbiased coverage of a large region around the Galactic Centre. Details are given for 183 methanol maser sites in the longitude range 345° through the Galactic Centre to 6°. Within 6° of the Galactic Centre, we found 88 maser sites, of which more than half (48) are new discoveries. The masers are confined to a narrow Galactic latitude range, indicative of many sources at the Galactic Centre distance and beyond, and confined to a thin disc population; there is no high-latitude population that might be ascribed to the Galactic bulge. Within 2° of the Galactic Centre the maser velocities all lie between −60 and +77 km s−1, a range much smaller than the 540 km s−1 range observed in CO. Elsewhere, the maser with highest positive velocity (+107 km s−1) occurs, surprisingly, near longitude 355° and is probably attributable to the Galactic bar. The maser with the most negative velocity (−127 km s−1) is near longitude 346°, within the longitude–velocity locus of the near side of the ‘3-kpc arm’. It has the most extreme velocity of a clear population of masers associated with the near and far sides of the 3-kpc arm. Closer to the Galactic Centre the maser space density is generally low, except within 0.25 kpc of the Galactic Centre itself, the ‘Galactic Centre zone’, where it is 50 times higher, which is hinted at by the longitude distribution, and confirmed by the unusual velocities.
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Background Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity. Objectives We sought to examine the effectiveness of episodic use of an inhaled ...corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing. Methods In a randomized, double-blind, placebo-controlled 12-month trial, 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension (1 mg twice daily), montelukast (4 mg daily), or placebo in addition to albuterol with each identified respiratory tract illness (RTI). Proportion of episode-free days (EFDs) during the 12-month trial was the primary outcome. Results The 3 treatment groups did not differ in proportions of EFDs, with adjusted mean EFDs of 76% (95% CI, 70% to 81%) for budesonide, 73% (95% CI, 66% to 79%) for montelukast, and 74% (95% CI, 65% to 81%) for conventional therapy ( P = .66). The 3 groups did not differ in oral corticosteroid use, health care use, quality of life, or linear growth. However, during RTIs, budesonide and montelukast therapy led to modest reductions in trouble breathing (38% P = .003 and 37% P = .003, respectively) and interference with activity scores (32% P = .01 and 40% P = .001, respectively) that were most evident in those with positive asthma predictive indices. Conclusions In preschool children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs, when added to albuterol, did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period. However, indicators of severity of acute illnesses were reduced, particularly in children with positive asthma predictive indices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
No studies have estimated the population-level burden of morbidity in individuals diagnosed with cancer as children (ages 0-19 years). We updated prevalence estimates of childhood cancer survivors as ...of 2011 and burden of morbidity in this population reflected by chronic conditions, neurocognitive dysfunction, compromised health-related quality of life, and health status (general health, mental health, functional impairment, functional limitations, pain, and fear/anxiety).
Surveillance, Epidemiology, and End Results (SEER) Program data from 1975 to 2011 were used to update the prevalence of survivors of childhood cancers in the United States. Childhood Cancer Survivor Study data were used to obtain estimates of morbidity burden indicators, which were then extrapolated to SEER data to obtain population-level estimates.
There were an estimated 388,501 survivors of childhood cancer in the United States as of January 1, 2011, of whom 83.5% are ≥5 years after diagnosis. The prevalence of any chronic condition among ≥5-year survivors ranged from 66% (ages 5-19) to 88% (ages 40-49). Estimates for specific morbidities ranged from 12% (pain) to 35% (neurocognitive dysfunction). Generally, morbidities increased by age. However, mental health and anxiety remained fairly stable, and neurocognitive dysfunction exhibited initial decline and then remained stable by time since diagnosis.
The estimated prevalence of survivors of childhood cancer is increasing, as is the estimated prevalence of morbidity in those ≥5 years after diagnosis.
Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority.
Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective We sought to assess the effectiveness ...and safety of BT in asthmatic patients 5 years after therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 trial ( ClinicalTrials.gov NCT01350414 ) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. Results One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting β2 -agonists.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
SN 2013dy is a Type Ia supernova (SN Ia) for which we have compiled an extraordinary data set spanning from 0.1 to ∼ 500 d after explosion. We present 10 epochs of ultraviolet (UV) through ...near-infrared (NIR) spectra with Hubble Space Telescope/Space Telescope Imaging Spectrograph, 47 epochs of optical spectra (15 of them having high resolution), and more than 500 photometric observations in the BVrRiIZYJH bands. SN 2013dy has a broad and slowly declining light curve (Δm
15(B) = 0.92 mag), shallow
$\mathrm{Si}\,\small {II}\,\lambda 6355$
absorption, and a low velocity gradient. We detect strong C ii in our earliest spectra, probing unburned progenitor material in the outermost layers of the SN ejecta, but this feature fades within a few days. The UV continuum of SN 2013dy, which is strongly affected by the metal abundance of the progenitor star, suggests that SN 2013dy had a relatively high-metallicity progenitor. Examining one of the largest single set of high-resolution spectra for an SN Ia, we find no evidence of variable absorption from circumstellar material. Combining our UV spectra, NIR photometry, and high-cadence optical photometry, we construct a bolometric light curve, showing that SN 2013dy had a maximum luminosity of
$10.0^{+4.8}_{-3.8} \times 10^{42}$
erg s−1. We compare the synthetic light curves and spectra of several models to SN 2013dy, finding that SN 2013dy is in good agreement with a solar-metallicity W7 model.
People who are food and nutrition insecure largely reside in Asia and Sub-Saharan Africa and for many, fish represents a rich source of protein, micronutrients and essential fatty acids. The ...contribution of fish to household food and nutrition security depends upon availability, access and cultural and personal preferences. Access is largely determined by location, seasonality and price but at the individual level it also depends upon a person's physiological and health status and how fish is prepared, cooked and shared among household members. The sustained and rapid expansion of aquaculture over the past 30 years has resulted in >40% of all fish now consumed being derived from farming. While aquaculture produce increasingly features in the diets of many Asians, it is much less apparent among those living in Sub-Saharan Africa. Here, per capita fish consumption has grown little and despite the apparently strong markets and adequate biophysical conditions, aquaculture has yet to develop. The contribution of aquaculture to food and nutrition security is not only just an issue of where aquaculture occurs but also of what is being produced and how and whether the produce is as accessible as that from capture fisheries. The range of fish species produced by an increasingly globalized aquaculture industry differs from that derived from capture fisheries. Farmed fishes are also different in terms of their nutrient content, a result of the species being grown and of rearing methods. Farmed fish price affects access by poor consumers while the size at which fish is harvested influences both access and use. This paper explores these issues with particular reference to Asia and Africa and the technical and policy innovations needed to ensure that fish farming is able to fulfil its potential to meet the global population's food and nutrition needs.
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