803 research outputs found
The World Bank and Its Critics: the Case of Sub-Saharan Africa
In 1981, as Sub-Saharan Africa continued in its downward spiral of economic demise, the World Bank issued a major study on the causes of Africa's economic woes and potential short-term steps to alleviate them. The World Bank's Accelerated Development in Sub-Saharan Africa: An Agenda for Action. In this paper, the authors dissect a number of the major controversies engendered by the World Bank Report, by presenting and evaluating the differences between the authors of the Report and critics of the Report.Center for Research on Economic Development, University of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/100718/1/ECON187.pd
What’s new since the April 2013 STIM IR Subcommittee Report to COLD: Hydra, Islandora and Dspace
Aaron Collier, Digital Repository Services Manager, Chancellor’s Office Suzanna Conrad, Digital Initiatives Librarian, Cal Poly Pomona Carmen Mitchell, Institutional Repository Librarian, CSU San Marcos Joan Parker, Librarian, Moss Landing Marine Laboratories Andrew Weiss, Digital Services Librarian, CSU Northridge
Jeremy Shellhase, Head of Information Services & Systems Department, Humboldt State Universit
Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer
Cà ncer de pròstata; Metà stasi neoplà sica; Immunoterà piaCáncer de próstata; Metástasis neoplásica; InmunoterapiaProstate cancer; Metastatic neoplasm; ImmunotherapyPURPOSE PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings.
PATIENTS AND METHODS Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events
(AWE)—namely, radiographic progression, pain progression, chemotherapy initiation, or death—at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned.
RESULTS At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89;
95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients.
CONCLUSION Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.Supported by Bavarian Nordic, the National Institute for Health Research Biomedical Research Centre at the Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research. Funded in part by National Cancer Institute Cancer Center Support Grant No. P30-CA008748 and the Center for Cancer Research, National Cancer Institute.P30 CA008748/CA/NCI NIH HHS/United States DH_/Department of Health/United Kingdo
The Ultraviolet Imaging Telescope: Instrument and Data Characteristics
The Ultraviolet Imaging Telescope (UIT) was flown as part of the Astro
observatory on the Space Shuttle Columbia in December 1990 and again on the
Space Shuttle Endeavor in March 1995. Ultraviolet (1200-3300 Angstroms) images
of a variety of astronomical objects, with a 40 arcmin field of view and a
resolution of about 3 arcsec, were recorded on photographic film. The data
recorded during the first flight are available to the astronomical community
through the National Space Science Data Center (NSSDC); the data recorded
during the second flight will soon be available as well. This paper discusses
in detail the design, operation, data reduction, and calibration of UIT,
providing the user of the data with information for understanding and using the
data. It also provides guidelines for analyzing other astronomical imagery made
with image intensifiers and photographic film.Comment: 44 pages, LaTeX, AAS preprint style and EPSF macros, accepted by PAS
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Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.
PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses
Dynamically avoiding fine-tuning the cosmological constant: the "Relaxed Universe"
We demonstrate that there exists a large class of action functionals of the
scalar curvature and of the Gauss-Bonnet invariant which are able to relax
dynamically a large cosmological constant (CC), whatever it be its starting
value in the early universe. Hence, it is possible to understand, without
fine-tuning, the very small current value of the CC as compared to its
theoretically expected large value in quantum field theory and string theory.
In our framework, this relaxation appears as a pure gravitational effect, where
no ad hoc scalar fields are needed. The action involves a positive power of a
characteristic mass parameter, M, whose value can be, interestingly enough, of
the order of a typical particle physics mass of the Standard Model of the
strong and electroweak interactions or extensions thereof, including the
neutrino mass. The model universe emerging from this scenario (the "Relaxed
Universe") falls within the class of the so-called LXCDM models of the cosmic
evolution. Therefore, there is a "cosmon" entity X (represented by an effective
object, not a field), which in this case is generated by the effective
functional and is responsible for the dynamical adjustment of the cosmological
constant. This model universe successfully mimics the essential past epochs of
the standard (or "concordance") cosmological model (LCDM). Furthermore, it
provides interesting clues to the coincidence problem and it may even connect
naturally with primordial inflation.Comment: LaTeX, 63 pp, 8 figures. Extended discussion. Version accepted in
JCA
Testing the running of the cosmological constant with Type Ia Supernovae at high z
Within the Quantum Field Theory context the idea of a "cosmological constant"
(CC) evolving with time looks quite natural as it just reflects the change of
the vacuum energy with the typical energy of the universe. In the particular
frame of Ref.[30], a "running CC" at low energies may arise from generic
quantum effects near the Planck scale, M_P, provided there is a smooth
decoupling of all massive particles below M_P. In this work we further develop
the cosmological consequences of a "running CC" by addressing the accelerated
evolution of the universe within that model. The rate of change of the CC stays
slow, without fine-tuning, and is comparable to H^2 M_P^2. It can be described
by a single parameter, \nu, that can be determined from already planned
experiments using SNe Ia at high z. The range of allowed values for \nu follow
mainly from nucleosynthesis restrictions. Present samples of SNe Ia can not yet
distinguish between a "constant" CC or a "running" one. The numerical
simulations presented in this work show that SNAP can probe the predicted
variation of the CC either ruling out this idea or confirming the evolution
hereafter expected.Comment: LaTeX, 51 pages, 13 figures, 1 table, references added, typos
corrected, version accepted in JCA
Predicting response and survival in chemotherapy-treated triple-negative breast cancer
In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not
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