593 research outputs found
Osteoporosis-related fracture case definitions for population-based administrative data
<p>Abstract</p> <p>Background</p> <p>Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions.</p> <p>Methods</p> <p>Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates.</p> <p>Results</p> <p>For hip fracture, sex-specific differences were observed in the magnitude of under- and over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions.</p> <p>Conclusions</p> <p>The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.</p
Functional immunomics: Microarray analysis of IgG autoantibody repertoires predicts the future response of NOD mice to an inducer of accelerated diabetes
One's present repertoire of antibodies encodes the history of one's past
immunological experience. Can the present autoantibody repertoire be consulted
to predict resistance or susceptibility to the future development of an
autoimmune disease? Here we developed an antigen microarray chip and used
bioinformatic analysis to study a model of type 1 diabetes developing in
non-obese diabetic (NOD) male mice in which the disease was accelerated and
synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We
obtained sera from 19 individual mice, treated the mice to induce
cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9
mice became severely diabetic while 10 mice permanently resisted diabetes. We
again obtained serum from each mouse afterCAD induction. We then analyzed the
patterns of antibodies in the individualmice to 266 different antigens spotted
on the antigen chip. We identified a select panel of 27 different antigens (10%
of the array) that revealed a pattern of IgG antibody reactivity in the pre-CAD
serathat discriminated between the mice resistant or susceptible to CAD with
100% sensitivity and 82% specificity (p=0.017). Surprisingly, the set of IgG
antibodies that was informative before CAD induction did not separate the
resistant and susceptible groups after the onset of CAD; new antigens became
criticalfor post-CAD repertoire discrimination. Thus, at least for a model
disease, present antibody repertoires can predict future disease; predictive
and diagnostic repertoires can differ; and decisive information about immune
system behavior can be mined by bioinformatic technology. Repertoires matter.Comment: See Advanced Publication on the PNAS website for final versio
The structure of SgrAI bound to DNA; recognition of an 8 base pair target
The three-dimensional X-ray crystal structure of the ‘rare cutting’ type II restriction endonuclease SgrAI bound to cognate DNA is presented. SgrAI forms a dimer bound to one duplex of DNA. Two Ca2+ bind in the enzyme active site, with one ion at the interface between the protein and DNA, and the second bound distal from the DNA. These sites are differentially occupied by Mn2+, with strong binding at the protein–DNA interface, but only partial occupancy of the distal site. The DNA remains uncleaved in the structures from crystals grown in the presence of either divalent cation. The structure of the dimer of SgrAI is similar to those of Cfr10I, Bse634I and NgoMIV, however no tetrameric structure of SgrAI is observed. DNA contacts to the central CCGG base pairs of the SgrAI canonical target sequence (CR|CCGGYG, | marks the site of cleavage) are found to be very similar to those in the NgoMIV/DNA structure (target sequence G|CCGGC). Specificity at the degenerate YR base pairs of the SgrAI sequence may occur via indirect readout using DNA distortion. Recognition of the outer GC base pairs occurs through a single contact to the G from an arginine side chain located in a region unique to SgrAI
Delay Of Insulin Addition To Oral Combination Therapy Despite Inadequate Glycemic Control: Delay of Insulin Therapy
BACKGROUND: Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control. OBJECTIVES: To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA(1c) goal was attained and maintained. DESIGN: Longitudinal observational cohort study. SUBJECTS: Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000. MEASUREMENTS: Subjects were followed until insulin was added, health plan disenrolment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%. RESULTS: During a mean follow-up of 54.6 ± 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%. CONCLUSIONS: Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy
Administrators in higher education: organizational expansion in a transforming institution
Recent European research has revealed growth in the number of administrators and professionals across different sections of universities—a long established trend in US universities. We build on this research by investigating the factors associated with variation in the proportion of administrators across 761 Higher Education Institutions (HEIs) in 11 European countries. We argue that the enactment of expanded and diversified missions of HE is one of the main factors nurturing universities’ profesional and administrative bodies. Our findings support such an assertion; regardless of geographical and institutional differences, HEIs with high levels of “entrepreneurialism” (e.g. in service provision and external engagement) are characterized by a larger proportion of administrative staff. However, we find no empirical support for arguments citing structural pressures and demands on HEIs due to higher student enrolments, budget cuts or deregulation as engines driving such change. Instead, our results point towards, as argued by neo-institutionalists, the diffusion of formal organization as a model of institutional identity and purpose, which is especially prevalent at high levels of external connectedness
Crystallographic and Molecular Dynamics Analysis of Loop Motions Unmasking the Peptidoglycan-Binding Site in Stator Protein MotB of Flagellar Motor
Background: The C-terminal domain of MotB (MotB-C) shows high sequence similarity to outer membrane protein A and related peptidoglycan (PG)-binding proteins. It is believed to anchor the power-generating MotA/MotB stator unit of the bacterial flagellar motor to the peptidoglycan layer of the cell wall. We previously reported the first crystal structure of this domain and made a puzzling observation that all conserved residues that are thought to be essential for PG recognition are buried and inaccessible in the crystal structure. In this study, we tested a hypothesis that peptidoglycan binding is preceded by, or accompanied by, some structural reorganization that exposes the key conserved residues. Methodology/Principal Findings: We determined the structure of a new crystalline form (Form B) of Helicobacter pylori MotB-C. Comparisons with the existing Form A revealed conformational variations in the petal-like loops around the carbohydrate binding site near one end of the b-sheet. These variations are thought to reflect natural flexibility at this site required for insertion into the peptidoglycan mesh. In order to understand the nature of this flexibility we have performed molecular dynamics simulations of the MotB-C dimer. The results are consistent with the crystallographic data and provide evidence that the three loops move in a concerted fashion, exposing conserved MotB residues that have previously been implicated in binding of the peptide moiety of peptidoglycan. Conclusion/Significance: Our structural analysis provides a new insight into the mechanism by which MotB inserts into th
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
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