217 research outputs found
USE OF ADR IN EXTENSION PUBLIC POLICY EDUCATION PROGRAMS AND ROLES EXTENSION CAN PLAY IN DISPUTE RESOLUTION
Teaching/Communication/Extension/Profession,
Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.
BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665
Measurement of Angular Distributions and R= sigma_L/sigma_T in Diffractive Electroproduction of rho^0 Mesons
Production and decay angular distributions were extracted from measurements
of exclusive electroproduction of the rho^0(770) meson over a range in the
virtual photon negative four-momentum squared 0.5< Q^2 <4 GeV^2 and the
photon-nucleon invariant mass range 3.8< W <6.5 GeV. The experiment was
performed with the HERMES spectrometer, using a longitudinally polarized
positron beam and a ^3He gas target internal to the HERA e^{+-} storage ring.
The event sample combines rho^0 mesons produced incoherently off individual
nucleons and coherently off the nucleus as a whole. The distributions in one
production angle and two angles describing the rho^0 -> pi+ pi- decay yielded
measurements of eight elements of the spin-density matrix, including one that
had not been measured before. The results are consistent with the dominance of
helicity-conserving amplitudes and natural parity exchange. The improved
precision achieved at 47 GeV,
reveals evidence for an energy dependence in the ratio R of the longitudinal to
transverse cross sections at constant Q^2.Comment: 15 pages, 15 embedded figures, LaTeX for SVJour(epj) document class
Revision: Fig. 15 corrected, recent data added to Figs. 10,12,14,15; minor
changes to tex
Exclusive Leptoproduction of rho^0 Mesons from Hydrogen at Intermediate Virtual Photon Energies
Measurements of the cross section for exclusive virtual-photoproduction of
rho^0 mesons from hydrogen are reported. The data were collected by the HERMES
experiment using 27.5 GeV positrons incident on a hydrogen gas target in the
HERA storage ring. The invariant mass W of the photon-nucleon system ranges
from 4.0 to 6.0 GeV, while the negative squared four-momentum Q^2 of the
virtual photon varies from 0.7 to 5.0 GeV^2. The present data together with
most of the previous data at W > 4 GeV are well described by a model that
infers the W-dependence of the cross section from the dependence on the Bjorken
scaling variable x of the unpolarized structure function for deep-inelastic
scattering. In addition, a model calculation based on Off-Forward Parton
Distributions gives a fairly good account of the longitudinal component of the
rho^0 production cross section for Q^2 > 2 GeV^2.Comment: 10 pages, 6 embedded figures, LaTeX for SVJour(epj) document class.
Revisions: curves added to Fig. 1, several clarifications added to tex
Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction
Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H,
3He, and 14N targets has been studied by the HERMES experiment at squared
four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20
GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the
nuclear transparency, was found to decrease with increasing coherence length of
quark-antiquark fluctuations of the virtual photon. The data provide clear
evidence of the interaction of the quark- antiquark fluctuations with the
nuclear medium.Comment: RevTeX, 5 pages, 3 figure
Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron
The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2]
for the proton and neutron have been determined from measurements of polarised
cross section asymmetries in deep inelastic scattering of 27.5 GeV
longitudinally polarised positrons from polarised 1H and 3He internal gas
targets. The data were collected in the region above the nucleon resonances in
the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the
proton the contribution to the generalised Gerasimov-Drell-Hearn integral was
found to be substantial and must be included for an accurate determination of
the full integral. Furthermore the data are consistent with a QCD
next-to-leading order fit based on previous deep inelastic scattering data.
Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte
BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers
Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers.
Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.
Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed.
Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations
Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.
BACKGROUND: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS: We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS: Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 × 10-40; RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85; P = 1.55 × 10-4; RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32-36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44-46% for BC, for carriers with two first-degree relatives diagnosed with BC. CONCLUSIONS: These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models
Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease
Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672
Reciprocal relationships between trajectories of depressive symptoms and screen media use during adolescence
Adolescents are constantly connected with each other and the digital landscape through a myriad of screen media devices. Unprecedented access to the wider world and hence a variety of activities, particularly since the introduction of mobile technology, has given rise to questions regarding the impact of this changing media environment on the mental health of young people. Depressive symptoms are one of the most common disabling health issues in adolescence and although research has examined associations between screen use and symptoms of depression, longitudinal investigations are rare and fewer still consider trajectories of change in symptoms. Given the plethora of devices and normalisation of their use, understanding potential longitudinal associations with mental health is crucial. A sample of 1,749 (47% female) adolescents (10-17 years) participated in six waves of data collection over two years. Symptoms of depression, time spent on screens, and on separate screen activities (social networking, gaming, web browsing, TV/passive) were self-reported. Latent growth curve modelling revealed three trajectories of depressive symptoms (Low-Stable, High-Decreasing, and Low-Increasing) and there were important differences across these groups on screen use. Some small, positive associations were evident between depressive symptoms and later screen use, and between screen use and later depressive symptoms. However, a Random Intercept Cross Lagged Panel Model revealed no consistent support for a longitudinal association. The study highlights the importance of considering differential trajectories of depressive symptoms and specific forms of screen activity to understand these relationships
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