3,436 research outputs found
The rationality of Sol manifolds
Let be the fundamental group of a manifold modeled on three
dimensional Sol geometry. We prove that has a finite index subgroup
which has a rational growth series with respect to a natural generating
set. We do this by enumerating by a regular language. However, in contrast
to most earlier proofs of this sort our regular language is not a language of
words in the generating set, but rather reflects a different geometric
structure in .Comment: 30 pages; author's name changed to agree with published version; to
appear in Journal of Algebr
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Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals.
BackgroundA previous analysis of 113 National Comprehensive Cancer NetworkÂź (NCCNÂź) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN GuidelinesÂź).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (nâ=â8) or were actually on-label (nâ=â5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies
Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.
Abstract
OBJECTIVE:
To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing.
METHODS:
Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510
7 10(6) cells/L).
RESULTS:
The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50
7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection.
CONCLUSION:
Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further.
CLASSIFICATION OF EVIDENCE:
This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses
The redshift evolution of bias and baryonic matter distribution
We study the distribution of baryonic and luminous matter within the
framework of a hierarchical scenario. Using an analytical model for structure
formation which has already been checked against observations for galaxies,
Lyman- clouds, clusters and reionization processes, we present its
predictions for the bias of these objects. We describe its dependence on the
luminosity (for galaxies or quasars) or the column density (for Lyman-
absorbers) of the considered objects. We also study its redshift evolution,
which can exhibit an intricate behaviour. These astrophysical objects do not
trace the dark matter density field, the Lyman- forest clouds being
undercorrelated and the bright galaxies overcorrelated, while the intermediate
class of Lyman-limit systems is seen to sample the matter field quite well.
We also present the distribution of baryonic matter over these various
objects. We show that light does not trace baryonic mass, since bright galaxies
which contain most of the stars only form a small fraction of the mass
associated with virialized and cooled halos. We consider two cosmologies: a
critical density universe and an open universe. In both cases, our results
agree with observations and show that hierarchical scenarios provide a good
model for structure formation and can describe a wide range of objects which
spans at least the seven orders of magnitude in mass for which data exist. More
detailed observations, in particular of the clustering evolution of galaxies,
will constrain the astrophysical models involved.Comment: 13 pages, final version published in A&
Phase Transitions of Charged Scalars at Finite Temperature and Chemical Potential
We calculate the grand canonical partition function at the one-loop level for
scalar quantum electrodynamics at finite temperature and chemical potential. A
classical background charge density with a charge opposite that of the scalars
ensures the neutrality of the system. For low density systems we find evidence
of a first order phase transition. We find upper and lower bounds on the
transition temperature below which the charged scalars form a condensate. A
first order phase transition may have consequences for helium-core white dwarf
stars in which it has been argued that such a condensate of charged helium-4
nuclei could exist.Comment: 20 pages, 3 figures. Version accepted for publication in JHE
Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)
Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery.
Methods/Design: Patients with stage 2â3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity †20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events.
Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery.
Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.Chief Scientist Office, Scotland (project ref no CZH/4/235), NHS GrampianPeer reviewedPublisher PD
On blocks of defect two and one simple module, and Lie algebra structure of HHÂč
Let k be a field of odd prime characteristic p. We calculate the Lie algebra structure of the first Hochschild cohomology of a class of quantum complete intersections over k. As a consequence, we prove that if B is a defect 2-block of a finite group algebra whose Brauer correspondent C has a unique isomorphism class of simple modules, then a basic algebra of B is a local algebra which can be generated by at most 2âI elements, where I is the inertial index of B, and where we assume that k is a splitting field for B and C
Stellar population gradients from cosmological simulations: dependence on mass and environment in local galaxies
The age and metallicity gradients for a sample of group and cluster galaxies
from N-body+hydrodynamical simulation are analyzed in terms of galaxy stellar
mass. Dwarf galaxies show null age gradient with a tail of high and positive
values for systems in groups and cluster outskirts. Massive systems have
generally zero age gradients which turn to positive for the most massive ones.
Metallicity gradients are distributed around zero in dwarf galaxies and become
more negative with mass; massive galaxies have steeper negative metallicity
gradients, but the trend flatten with mass. In particular, fossil groups are
characterized by a tighter distribution of both age and metallicity gradients.
We find a good agreement with both local observations and independent
simulations. The results are also discussed in terms of the central age and
metallicity, as well as the total colour, specific star formation and velocity
dispersion.Comment: 9 pages, 5 figures, accepted for publication on MNRA
International lease accounting reform and economic consequences: the views of UK users and preparers
In response to perceived difficulties with extant lease-accounting standards in operation worldwide, the G4+1 issued a discussion paper which proposes that all leases should be recognized on the balance sheet [ASB (1999). Leases: Implementation of a new approach, discussion paper. London: Accounting Standards Board]. Leasing is now on the active agenda of the IASB. A major difficulty faced by standard setters lies in overcoming the preparer/user lobbying imbalance and obtaining ex ante evidence on the likely impact of regulatory reform. This paper contributes to the ongoing international debate by conducting a questionnaire survey of U.K. users and preparers to assess their views on proposals for lease-accounting reform and on the potential economic consequences of their adoption. The results, based on 132 responses, indicate that both groups accept that there are deficiencies in the current rules, but they do not agree on the way forward and believe that the proposals would lead to significant economic consequences for key parties. The impact on respondents' views of familiarity with the proposals, level of lease usage, and company size, is also examined
The mass assembly of galaxy groups and the evolution of the magnitude gap
We investigate the assembly of groups and clusters of galaxies using the
Millennium dark matter simulation and the associated gas simulations and
semi-analytic catalogues of galaxies. In particular, in order to find an
observable quantity that could be used to identify early-formed groups, we
study the development of the difference in magnitude between their brightest
galaxies to assess the use of magnitude gaps as possible indicators. We select
galaxy groups and clusters at redshift z=1 with dark matter halo mass M(R200) >
1E13/h Msun, and trace their properties until the present time (z=0). We
consider only the systems with X-ray luminosity L_X> 0.25E42/h^2 erg/s at z=0.
While it is true that a large magnitude gap between the two brightest galaxies
of a particular group often indicates that a large fraction of its mass was
assembled at an early epoch, it is not a necessary condition. More than 90% of
fossil groups defined on the basis of their magnitude gaps (at any epoch
between 0<z<1) cease to be fossils within 4 Gyr, mostly because other massive
galaxies are assembled within their cores, even though most of the mass in
their haloes might have been assembled at early times. We show that, compared
to the conventional definition of fossil galaxy groups based on the magnitude
gap Delta m(12)> 2 (in the R-band, within 0.5R200 of the centre of the group),
an alternative criterion Delta m(14)>2.5 (within the same radius) finds 50%
more early-formed systems, and those that on average retain their fossil phase
longer. However, the conventional criterion performs marginally better at
finding early-formed groups at the high-mass end of groups. Nevertheless, both
criteria fail to identify a majority of the early-formed systems.Comment: 16 pages, 11 figures, 2 tables. Accepted for publication in MNRA
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