173 research outputs found
Lentiviral gene therapy corrects platelet phenotype and function in patients with Wiskott-Aldrich syndrome
BACKGROUND:
Thrombocytopenia is a serious issue for all patients with classical Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) because it causes severe and life-threatening bleeding. Lentiviral gene therapy (GT) for WAS has shown promising results in terms of immune reconstitution. However, despite the reduced severity and frequency of bleeding events, platelet counts remain low in GT-treated patients.
OBJECTIVE:
We carefully investigated platelet defects in terms of phenotype and function in untreated patients with WAS and assessed the effect of GT treatment on platelet dysfunction.
METHODS:
We analyzed a cohort of 20 patients with WAS/XLT, 15 of them receiving GT. Platelet phenotype and function were analyzed by using electron microscopy, flow cytometry, and an aggregation assay. Platelet protein composition was assessed before and after GT by means of proteomic profile analysis.
RESULTS:
We show that platelets from untreated patients with WAS have reduced size, abnormal ultrastructure, and a hyperactivated phenotype at steady state, whereas activation and aggregation responses to agonists are decreased. GT restores platelet size and function early after treatment and reduces the hyperactivated phenotype proportionally to WAS protein expression and length of follow-up.
CONCLUSIONS:
Our study highlights the coexistence of morphologic and multiple functional defects in platelets lacking WAS protein and demonstrates that GT normalizes the platelet proteomic profile with consequent restoration of platelet ultrastructure and phenotype, which might explain the observed reduction of bleeding episodes after GT. These results are instrumental also from the perspective of a future clinical trial in patients with XLT only presenting with microthrombocytopenia
Alcohol and cannabis use among adolescents in Flemish secondary school in Brussels: effects of type of education
<p>Abstract</p> <p>Background</p> <p>Research regarding socio-economic differences in alcohol and drug use in adolescence yields mixed results. This study hypothesizes that (1) when using education type as a proxy of one's social status, clear differences will exist between students from different types of education, regardless of students' familial socio-economic background; (2) and that the effects of education type differ according to their cultural background.</p> <p>Methods</p> <p>Data from the Brussels youth monitor were used, a school survey administered among 1,488 adolescents from the 3rd to 6th year of Flemish secondary education. Data were analyzed using multilevel logistic regression models.</p> <p>Results</p> <p>Controlling for their familial background, the results show that native students in lower educational tracks use alcohol and cannabis more often than students in upper educational tracks. Such a relationship was not found for students from another ethnic background.</p> <p>Conclusion</p> <p>Results from this study indicate that research into health risks should take into account both adolescents' familial background and individual social position as different components of youngsters' socio-economic background.</p
“When I Was Circumcised I Was Taught Certain Things”: Risk Compensation and Protective Sexual Behavior among Circumcised Men in Kisumu, Kenya
Background: Male circumcision has been shown to reduce the transmission of HIV from women to men through vaginal sex by approximately 60%. There is concern that men may engage in risk compensation after becoming circumcised, diminishing the benefits of male circumcision. Methods and Findings: We conducted qualitative interviews with 30 sexually active circumcised men in Kisumu, Kenya from March to November 2008. Most respondents reported no behavior change or increasing protective sexual behaviors including increasing condom use and reducing the number of sexual partners. A minority of men reported engaging in higher risk behaviors either not using condoms or increasing the number of sex partners. Circumcised respondents described being able to perform more rounds of sex, easier condom use, and fewer cuts on the penis during sex. Conclusions: Results illustrate that information about MC’s protection against HIV has disseminated into the larger community and MC accompanied by counseling and HIV testing can foster positive behavior change and maintain sexua
AIDS knowledge and sexual activity among Flemish secondary school students: a multilevel analysis of the effects of type of education
<p>Abstract</p> <p>Background</p> <p>The behavior of adolescents puts them at an increased risk for HIV and other STIs, and their knowledge about HIV/AIDS is often inadequate. An understanding of how AIDS knowledge and sexual activity co-vary among Flemish secondary school students and of how education type, specifically, affects these students is limited. This study addresses the question of whether the effects of education type on HIV/AIDS knowledge and sexual activity are independent of the socio-demographic characteristics of the students.</p> <p>Methods</p> <p>Data from the Flemish Educational Assessment survey, which collected data from a large representative sample of third- and fifth-grade high school students (<it>N </it>= 11,872), were used. Data were analyzed using multilevel logistic and Poisson regression techniques.</p> <p>Results</p> <p>There is an indication that type of education affects both an adolescent's sexual activity and his/her AIDS knowledge; these effects prove robust for differences in socio-economic backgrounds. Students in lower status education types are more likely to be sexually active and to have poorer AIDS knowledge. The relationship between AIDS knowledge and sexual activity is, however, more complex. Although students in education types with poorer AIDS knowledge are more sexually active, within each of these groups the sexually active have better AIDS knowledge than the non-sexually active. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p> <p>Conclusion</p> <p>These findings are consistent with the literature on the role of the educational system in the reproduction of social inequalities. Students from lower status education types are at increased sexual risk compared to those from higher status types. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p
Lowering IceCube’s energy threshold for point source searches in the southern sky
Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background
The IceCube Neutrino Observatory: Instrumentation and Online Systems
The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy
neutrino detector built into the ice at the South Pole. Construction of
IceCube, the largest neutrino detector built to date, was completed in 2011 and
enabled the discovery of high-energy astrophysical neutrinos. We describe here
the design, production, and calibration of the IceCube digital optical module
(DOM), the cable systems, computing hardware, and our methodology for drilling
and deployment. We also describe the online triggering and data filtering
systems that select candidate neutrino and cosmic ray events for analysis. Due
to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are
operating and collecting data. IceCube routinely achieves a detector uptime of
99% by emphasizing software stability and monitoring. Detector operations have
been stable since construction was completed, and the detector is expected to
operate at least until the end of the next decade.Comment: 83 pages, 50 figures; updated with minor changes from journal review
and proofin
All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data
Since the recent detection of an astrophysical flux of high energy neutrinos,
the question of its origin has not yet fully been answered. Much of what is
known about this flux comes from a small event sample of high neutrino purity,
good energy resolution, but large angular uncertainties. In searches for
point-like sources, on the other hand, the best performance is given by using
large statistics and good angular reconstructions. Track-like muon events
produced in neutrino interactions satisfy these requirements. We present here
the results of searches for point-like sources with neutrinos using data
acquired by the IceCube detector over seven years from 2008--2015. The
discovery potential of the analysis in the northern sky is now significantly
below , on average
lower than the sensitivity of the previously published analysis of four
years exposure. No significant clustering of neutrinos above background
expectation was observed, and implications for prominent neutrino source
candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical
Journa
Neutrinos and Cosmic Rays Observed by IceCube
The core mission of the IceCube Neutrino observatory is to study the origin
and propagation of cosmic rays. IceCube, with its surface component IceTop,
observes multiple signatures to accomplish this mission. Most important are the
astrophysical neutrinos that are produced in interactions of cosmic rays, close
to their sources and in interstellar space. IceCube is the first instrument
that measures the properties of this astrophysical neutrino flux, and
constrains its origin. In addition, the spectrum, composition and anisotropy of
the local cosmic-ray flux are obtained from measurements of atmospheric muons
and showers. Here we provide an overview of recent findings from the analysis
of IceCube data, and their implications on our understanding of cosmic rays.Comment: Review article, to appear in Advances in Space Research, special
issue "Origins of Cosmic Rays
Observation and Characterization of a Cosmic Muon Neutrino Flux from the Northern Hemisphere using six years of IceCube data
The IceCube Collaboration has previously discovered a high-energy
astrophysical neutrino flux using neutrino events with interaction vertices
contained within the instrumented volume of the IceCube detector. We present a
complementary measurement using charged current muon neutrino events where the
interaction vertex can be outside this volume. As a consequence of the large
muon range the effective area is significantly larger but the field of view is
restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have
been analyzed using a likelihood approach based on the reconstructed muon
energy and zenith angle. At the highest neutrino energies between 191 TeV and
8.3 PeV a significant astrophysical contribution is observed, excluding a
purely atmospheric origin of these events at significance. The
data are well described by an isotropic, unbroken power law flux with a
normalization at 100 TeV neutrino energy of
and a hard spectral index of . The observed spectrum is
harder in comparison to previous IceCube analyses with lower energy thresholds
which may indicate a break in the astrophysical neutrino spectrum of unknown
origin. The highest energy event observed has a reconstructed muon energy of
which implies a probability of less than 0.005% for
this event to be of atmospheric origin. Analyzing the arrival directions of all
events with reconstructed muon energies above 200 TeV no correlation with known
-ray sources was found. Using the high statistics of atmospheric
neutrinos we report the currently best constraints on a prompt atmospheric muon
neutrino flux originating from charmed meson decays which is below in
units of the flux normalization of the model in Enberg et al. (2008).Comment: 20 pages, 21 figure
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