367 research outputs found
Setting priorities for a research agenda to combat drug-resistant tuberculosis in children
Setting: Numerous knowledge gaps hamper the prevention and treatment of childhood drug-resistant tuberculosis (TB). Identifying research priorities is vital to inform and develop strategies to address this neglected problem. Objective: To systematically identify and rank research priorities in childhood drug-resistant TB. Design: Adapting the Child Health and Nutrition Research Initiative (CHNRI) methodology, we compiled 53 research questions in four research areas, then classified the questions into three research types. We invited experts in childhood drug-resistant TB to score these questions through an online survey. Results: A total of 81 respondents participated in the survey. The top-ranked research question was to identify the best combination of existing diagnostic tools for early diagnosis. Highly ranked treatment-related questions centred on the reasons for and interventions to improve treatment outcomes, adverse effects of drugs and optimal treatment duration. The prevalence of drug-resistant TB was the highest-ranked question in the epidemiology area. The development type questions that ranked highest focused on interventions for optimal diagnosis, treatment and modalities for treatment delivery. Conclusion: This is the first effort to identify and rank research priorities for childhood drug-resistant TB. The result is a resource to guide research to improve prevention and treatment of drug-resistant TB in children
The 2HWC HAWC Observatory Gamma Ray Catalog
We present the first catalog of TeV gamma-ray sources realized with the
recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the
most sensitive wide field-of-view TeV telescope currently in operation, with a
1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an
instantaneous field of view >1.5 sr and >90% duty cycle, it continuously
surveys and monitors the sky for gamma ray energies between hundreds GeV and
tens of TeV.
HAWC is located in Mexico at a latitude of 19 degree North and was completed
in March 2015. Here, we present the 2HWC catalog, which is the result of the
first source search realized with the complete HAWC detector. Realized with 507
days of data and represents the most sensitive TeV survey to date for such a
large fraction of the sky. A total of 39 sources were detected, with an
expected contamination of 0.5 due to background fluctuation. Out of these
sources, 16 are more than one degree away from any previously reported TeV
source. The source list, including the position measurement, spectrum
measurement, and uncertainties, is reported. Seven of the detected sources may
be associated with pulsar wind nebulae, two with supernova remnants, two with
blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa
The Sensitivity of HAWC to High-Mass Dark Matter Annihilations
The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view
detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in
central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC
will observe gamma rays and cosmic rays with an array of water Cherenkov
detectors. The full HAWC array is scheduled to be operational in Spring 2015.
In this paper, we study the HAWC sensitivity to the gamma-ray signatures of
high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be
sensitive to diverse searches for dark matter annihilation, including
annihilation from extended dark matter sources, the diffuse gamma-ray emission
from dark matter annihilation, and gamma-ray emission from non-luminous dark
matter subhalos. Here we consider the HAWC sensitivity to a subset of these
sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the
Galactic center. We simulate the HAWC response to gamma rays from these sources
in several well-motivated dark matter annihilation channels. If no gamma-ray
excess is observed, we show the limits HAWC can place on the dark matter
cross-section from these sources. In particular, in the case of dark matter
annihilation into gauge bosons, HAWC will be able to detect a narrow range of
dark matter masses to cross-sections below thermal. HAWC should also be
sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The
constraints placed by HAWC on the dark matter cross-section from known sources
should be competitive with current limits in the mass range where HAWC has
similar sensitivity. HAWC can additionally explore higher dark matter masses
than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR
Association of concomitant bone resorption inhibitors with overall survival among patients with metastatic castration-resistant prostate cancer and bone metastases receiving abiraterone acetate with prednisone as first-line therapy.
The search for transient astrophysical neutrino emission with IceCube-DeepCore
We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae
Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
A search for high-energy neutrinos interacting within the IceCube detector
between 2010 and 2012 provided the first evidence for a high-energy neutrino
flux of extraterrestrial origin. Results from an analysis using the same
methods with a third year (2012-2013) of data from the complete IceCube
detector are consistent with the previously reported astrophysical flux in the
100 TeV - PeV range at the level of per flavor and reject a
purely atmospheric explanation for the combined 3-year data at .
The data are consistent with expectations for equal fluxes of all three
neutrino flavors and with isotropic arrival directions, suggesting either
numerous or spatially extended sources. The three-year dataset, with a livetime
of 988 days, contains a total of 37 neutrino candidate events with deposited
energies ranging from 30 to 2000 TeV. The 2000 TeV event is the highest-energy
neutrino interaction ever observed.Comment: 8 pages, 5 figures. Accepted by PRL. The event catalog, event
displays, and other data tables are included after the final page of the
article. Changed from the initial submission to reflect referee comments,
expanding the section on atmospheric backgrounds, and fixes offsets of up to
0.9 seconds in reported event times. Address correspondence to: J. Feintzeig,
C. Kopper, N. Whitehor
Restricted dispersal in a sea of gene flow
Howfar domarine larvae disperse in the ocean? Decades of population genetic
studies have revealed generally low levels of genetic structure at large spatial
scales (hundreds of kilometres). Yet this result, typically based on discrete
sampling designs, does not necessarily imply extensive dispersal. Here, we
adopt a continuous sampling strategy along 950 km of coast in the northwestern
Mediterranean Sea to address this question in four species. In line
with expectations, we observe weak genetic structure at a large spatial scale.
Nevertheless, our continuous sampling strategy uncovers a pattern of isolation
by distance at small spatial scales (few tens of kilometres) in two species. Individual-
based simulations indicate that this signal is an expected signature of
restricted dispersal. At the other extreme of the connectivity spectrum, two
pairs of individuals that are closely related genetically were found more
than 290 km apart, indicating long-distance dispersal. Such a combination of
restricted dispersal with rare long-distance dispersal events is supported by
a high-resolution biophysical model of larval dispersal in the study area,
and we posit that it may be common in marine species. Our results bridge
population genetic studies with direct dispersal studies and have implications
for the design of marine reserve networksVersiĂłn del edito
Clinical standards for drug-susceptible TB in children and adolescents
BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents. METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document. RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent. CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.National Institutes of HealthRevisiĂłn por pare
The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models
Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)
Male gonadal dose of ionizing radiation delivered during X-ray examinations and monthly probability of pregnancy: a population-based retrospective study
BACKGROUND: Male gonadal exposure to ionizing radiation may disrupt spermatogenesis, but its influence on the fecundity of couples has been rarely studied. We aimed to characterize the influence of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy. METHODS: We recruited a random sample of women who retrospectively described 1110 periods of unprotected intercourse beginning between 1985 and 1999 and leading either to a live birth or to no pregnancy; their duration was censored after 13 months. The male partner answered a telephone questionnaire on radiodiagnostic examinations. We assigned a mean gonadal dose to each type of radiodiagnostic examination. We defined male dose for each period of unprotected intercourse as the sum of the gonadal doses of the X-ray examinations experienced between 18 years of age and the date of discontinuation of contraception. Time to pregnancy was analysed using a discrete Cox model with random effect allowing to estimate hazard ratios of pregnancy. RESULTS: After adjustment for female factors likely to influence fecundity, there was no evidence of an association between male dose and the probability of pregnancy (test of homogeneity, p = 0.55). When compared to couples with a male gonadal dose between 0.01 and 0.20 milligrays (n = 321 periods of unprotected intercourse), couples with a gonadal dose above 10 milligrays had a hazard ratio of pregnancy of 1.44 (95% confidence interval, 0.73â2.86, n = 31). CONCLUSION: Our study provides no evidence of a long-term detrimental effect of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy during the year following discontinuation of contraceptive use. Classification errors due to the retrospective assessment of male gonadal exposure may have limited the statistical power of our study
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