190 research outputs found
Quantum geometry of 2d gravity coupled to unitary matter
We show that there exists a divergent correlation length in 2d quantum
gravity for the matter fields close to the critical point provided one uses the
invariant geodesic distance as the measure of distance. The corresponding
reparameterization invariant two-point functions satisfy all scaling relations
known from the ordinary theory of critical phenomena and the KPZ exponents are
determined by the power-like fall off of these two-point functions. The only
difference compared to flat space is the appearance of a dynamically generated
fractal dimension d_h in the scaling relations. We analyze numerically the
fractal properties of space-time for Ising and three-states Potts model coupled
to 2d dimensional quantum gravity using finite size scaling as well as small
distance scaling of invariant correlation functions. Our data are consistent
with d_h=4, but we cannot rule out completely the conjecture d_H =
-2\alpha_1/\alpha_{-1}, where \alpha_{-n} is the gravitational dressing
exponent of a spin-less primary field of conformal weight (n+1,n+1). We compute
the moments and the loop-length distribution function and show that the
fractal properties associated with these observables are identical, with good
accuracy, to the pure gravity case.Comment: LaTeX2e, 38 pages, 13 figures, 32 eps files, added one referenc
Patient and physician factors associated with participation in cervical and uterine cancer trials: An NRG/GOG247 study
AbstractPurposeThe aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.MethodsProspective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported.ResultsSixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7–11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3–46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1–999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9–>1000), concern about care if not on trial (OR12.1; CI 2.1–71.4), pressure to enroll (OR .27; CI 0.12–.64), caregiving without pay (OR 0.13; CI .02–.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6–8.4), and trial would not be time consuming (OR 3.3; CI 1.3–8.1).ConclusionsTrial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials
Cosmological parameters from SDSS and WMAP
We measure cosmological parameters using the three-dimensional power spectrum
P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in
combination with WMAP and other data. Our results are consistent with a
``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt,
tensor modes or massive neutrinos. Adding SDSS information more than halves the
WMAP-only error bars on some parameters, tightening 1 sigma constraints on the
Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter
density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on
neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when
dropping prior assumptions about curvature, neutrinos, tensor modes and the
equation of state. Our results are in substantial agreement with the joint
analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive
consistency check with independent redshift survey data and analysis
techniques. In this paper, we place particular emphasis on clarifying the
physical origin of the constraints, i.e., what we do and do not know when using
different data sets and prior assumptions. For instance, dropping the
assumption that space is perfectly flat, the WMAP-only constraint on the
measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to
t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running
tilt, neutrino mass and equation of state in the list of free parameters, many
constraints are still quite weak, but future cosmological measurements from
SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt
figures available at http://www.hep.upenn.edu/~max/sdsspars.htm
Does a lack of physical activity explain the rheumatoid arthritis lipid profile?
Abstract Background In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile. Methods NMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined. Results Subjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05). Conclusions The RA-associated lipoprotein profile is associated with a lack of physical activity. As this was a cross-sectional investigation and not an intervention and was performed from 2008–13, this study was not registered in clinicaltrials.gov
Patient and physician factors associated with participation in cervical and uterine cancer trials: An NRG/GOG247 study
To identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials
Epitope length variants balance protective immune responses and viral escape in HIV-1 infection
Cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a single optimal 10-mer epitope (KK10) in the human immunodeficiency virus type-1 (HIV-1) protein p24Gag are associated with enhanced immune control in patients expressing human leukocyte antigen (HLA)-B∗27:05. We find that proteasomal activity generates multiple length variants of KK10 (4–14 amino acids), which bind TAP and HLA-B∗27:05. However, only epitope forms ≥8 amino acids evoke peptide length-specific and cross-reactive CTL responses. Structural analyses reveal that all epitope forms bind HLA-B∗27:05 via a conserved N-terminal motif, and competition experiments show that the truncated epitope forms outcompete immunogenic epitope forms for binding to HLA-B∗27:05. Common viral escape mutations abolish (L136M) or impair (R132K) production of KK10 and longer epitope forms. Peptide length influences how well the inhibitory NK cell receptor KIR3DL1 binds HLA-B∗27:05 peptide complexes and how intraepitope mutations affect this interaction. These results identify a viral escape mechanism from CTL and NK responses based on differential antigen processing and peptide competition
Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis
Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known
Biallelic variants in KIF14 cause intellectual disability with microcephaly.
Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle localization of the mitotic citron rho-interacting kinase, CIT, also mutated in microcephaly. Our results demonstrate the involvement of KIF14 in development and reveal a wide phenotypic variability ranging from fetal lethality to moderate developmental delay and microcephaly
Isotopic signatures of methane emissions from tropical fires, agriculture and wetlands: the MOYA and ZWAMPS flights
We report methane isotopologue data from aircraft and ground measurements in Africa and South America. Aircraft campaigns sampled strong methane fluxes over tropical papyrus wetlands in the Nile, Congo and Zambezi basins, herbaceous wetlands in Bolivian southern Amazonia, and over fires in African woodland, cropland and savannah grassland. Measured methane δ13CCH4 isotopic signatures were in the range −55 to −49‰ for emissions from equatorial Nile wetlands and agricultural areas, but widely −60 ± 1‰ from Upper Congo and Zambezi wetlands. Very similar δ13CCH4 signatures were measured over the Amazonian wetlands of NE Bolivia (around −59‰) and the overall δ13CCH4 signature from outer tropical wetlands in the southern Upper Congo and Upper Amazon drainage plotted together was −59 ± 2‰. These results were more negative than expected. For African cattle, δ13CCH4 values were around −60 to −50‰. Isotopic ratios in methane emitted by tropical fires depended on the C3 : C4 ratio of the biomass fuel. In smoke from tropical C3 dry forest fires in Senegal, δ13CCH4 values were around −28‰. By contrast, African C4 tropical grass fire δ13CCH4 values were −16 to −12‰. Methane from urban landfills in Zambia and Zimbabwe, which have frequent waste fires, had δ13CCH4 around −37 to −36‰. These new isotopic values help improve isotopic constraints on global methane budget models because atmospheric δ13CCH4 values predicted by global atmospheric models are highly sensitive to the δ13CCH4 isotopic signatures applied to tropical wetland emissions. Field and aircraft campaigns also observed widespread regional smoke pollution over Africa, in both the wet and dry seasons, and large urban pollution plumes. The work highlights the need to understand tropical greenhouse gas emissions in order to meet the goals of the UNFCCC Paris Agreement, and to help reduce air pollution over wide regions of Africa
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases
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