134 research outputs found
SYMPOSIUM: Legal and Community Services Advocates Working Together To Preserve Families, Columbia University School of Law, December 1-2, 1994
Exploring the involvement of NLRP3 and Il-1β in Osteoarthritis of the Hand: Results from a Pilot Study
Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1 plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1 and NLRP3, the serum levels of IL-1, IL-6, IL-17, and tumor necrosis factor- (TNF-) , and the protein levels of IL-1 and NLRP3. We also assessed the relationships between IL-1 and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1 and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1, IL-6, IL-17, and TNF- serum levels were determined by ELISA. IL-1 gene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p=0.0063) and EHOA groups (p=0.0038). IL-1 serum levels were not significantly different across the groups; IL-6, IL-17, and TNF- were not detectable in any sample. IL-1 concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r=-0.446; p=0.0008) and in NEHOA (r=-0.608; p=0.004), while IL-1 gene expression was positively correlated with the number of joint swellings in the EHOA group (r=0.512; p=0.011). Taken together, our results, showing poorly detectable IL-1 concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level
Suboptimal antiretroviral therapy adherence among HIV-infected adults in Guangzhou, China
Despite China“s free antiretroviral treatment (ART) program, there are high rates of treatment failure, large sociodemographic disparities in care outcomes and emerging medication resistance. Understanding patient medication adherence behaviors and challenges could inform adherence interventions to maximize the individual and prevention benefits of ART. This study assessed recent non-adherence and treatment interruption among 813 HIV-infected adult outpatients in Guangzhou, China. Participants completed a behavioral survey, underwent chart review, and were tested for syphilis, gonorrhea, and chlamydia. Factors associated with suboptimal adherence were identified using univariate and multivariate logistic regression. Among 721 HIV-infected adults receiving ART, 18.9% reported recent non-adherence (any missed ART in the past 4 weeks) and 6.8% reported treatment interruption (four or more weeks of missed ART in the past year). Lower education, living alone, alcohol use and being on ART one to three years were associated with recent non-adherence. Male gender, lower education and being on ART one to three years were associated with treatment interruption. ART medication adherence interventions are needed in China that include individualized, long-term adherence plans sensitive to patients“ educational and economic situations. These interventions should also consider possible gender disparities in treatment outcomes and address the use of alcohol during ART. Successful ART medication adherence interventions in China can inform other international settings that face similar adherence challenges and disparities
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GLIMMER: A Randomized Phase 2b Dose-Ranging Trial of Linerixibat in Primary Biliary Cholangitis Patients With Pruritus
Background & aims: GLIMMER assessed dose-response, efficacy, and safety of linerixibat, an ileal bile acid transporter inhibitor in development for cholestatic pruritus associated with primary biliary cholangitis (PBC).
Methods: GLIMMER was a Phase 2b, multicenter, randomized, parallel-group study in adults with PBC and moderate-to-severe pruritus (≥4 on 0-10 numerical rating scale [NRS]). After 4 weeks of single-blind placebo, patients with NRS ≥3 were randomized (4:1) to double-blind linerixibat/placebo for 12 weeks (to week 16), followed by single-blind placebo (to week 20). The primary objective was to investigate dose-related changea in mean worst daily itch (MWDI) score.
Results: One hundred forty-seven patients received placebo (n = 36) or linerixibat (once daily: 20 mg, n = 16; 90 mg, n = 23; 180 mg, n = 27; twice daily: 40 mg, n = 23; 90 mg, n = 22). Linerixibat groups exhibited ≥2-point mean reductions in MWDI from baseline at week 16; however, differences from placebo were not significant. Post hoc analysis of change from baseline in monthly itch score over the treatment period (Phase 3 endpoint) showed significant differences between placebo and linerixibat 180 mg once daily (P = .0424), 40 mg twice daily (P = .0105), and 90 mg twice daily (P = .0370). A significant relationship between total daily dose and response was observed post hoc in the per protocol population (P = .0542). Consistent with mechanism of action, diarrhea was the most frequent adverse event, and incidence increased with dose.
Conclusions: Linerixibat effect on itch was not significantly different versus placebo in the primary intent-to-treat analysis but was associated with a significant dose-dependent reduction in itch in the per protocol population. A well-tolerated dose was identified for Phase 3 investigation for cholestatic pruritus in PBC.
Clinicaltrials: gov ID: NCT02966834.
Keywords: Bile Acids; Cholestatic Pruritus; Clinical Trial; IBAT Inhibitor; Patient-Reported Outcomes
Risk factors and outcomes associated with community-onset and hospital-acquired coinfection in patients hospitalized for coronavirus disease 2019 (COVID-19): A multihospital cohort study
BACKGROUND: We sought to determine the incidence of community-onset and hospital-acquired coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19) and to evaluate associated predictors and outcomes.
METHODS: In this multicenter retrospective cohort study of patients hospitalized for COVID-19 from March 2020 to August 2020 across 38 Michigan hospitals, we assessed prevalence, predictors, and outcomes of community-onset and hospital-acquired coinfections. In-hospital and 60-day mortality, readmission, discharge to long-term care facility (LTCF), and mechanical ventilation duration were assessed for patients with versus without coinfection.
RESULTS: Of 2,205 patients with COVID-19, 141 (6.4%) had a coinfection: 3.0% community onset and 3.4% hospital acquired. Of patients without coinfection, 64.9% received antibiotics. Community-onset coinfection predictors included admission from an LTCF (OR, 3.98; 95% CI, 2.34-6.76; P \u3c .001) and admission to intensive care (OR, 4.34; 95% CI, 2.87-6.55; P \u3c .001). Hospital-acquired coinfection predictors included fever (OR, 2.46; 95% CI, 1.15-5.27; P = .02) and advanced respiratory support (OR, 40.72; 95% CI, 13.49-122.93; P \u3c .001). Patients with (vs without) community-onset coinfection had longer mechanical ventilation (OR, 3.31; 95% CI, 1.67-6.56; P = .001) and higher in-hospital mortality (OR, 1.90; 95% CI, 1.06-3.40; P = .03) and 60-day mortality (OR, 1.86; 95% CI, 1.05-3.29; P = .03). Patients with (vs without) hospital-acquired coinfection had higher discharge to LTCF (OR, 8.48; 95% CI, 3.30-21.76; P \u3c .001), in-hospital mortality (OR, 4.17; 95% CI, 2.37-7.33; P ≤ .001), and 60-day mortality (OR, 3.66; 95% CI, 2.11-6.33; P ≤ .001).
CONCLUSION: Despite community-onset and hospital-acquired coinfection being uncommon, most patients hospitalized with COVID-19 received antibiotics. Admission from LTCF and to ICU were associated with increased risk of community-onset coinfection. Future studies should prospectively validate predictors of COVID-19 coinfection to facilitate the reduction of antibiotic use
The NANOGrav 11-Year Data Set: Arecibo Observatory Polarimetry And Pulse Microcomponents
We present the polarization pulse profiles for 28 pulsars observed with the
Arecibo Observatory by the North American Nanohertz Observatory for
Gravitational Waves (NANOGrav) timing project at 2.1 GHz, 1.4 GHz, and 430 MHz.
These profiles represent some of the most sensitive polarimetric millisecond
pulsar profiles to date, revealing the existence of microcomponents (that is,
pulse components with peak intensities much lower than the total pulse peak
intensity). Although microcomponents have been detected in some pulsars
previously, we present microcomponents for PSRs B1937+21, J1713+0747, and
J2234+0944 for the first time. These microcomponents can have an impact on
pulsar timing, geometry, and flux density determination. We present rotation
measures for all 28 pulsars, determined independently at different observation
frequencies and epochs, and find the Galactic magnetic fields derived from
these rotation measures to be consistent with current models. These
polarization profiles were made using measurement equation template matching,
which allows us to generate the polarimetric response of the Arecibo
Observatory on an epoch-by-epoch basis. We use this method to describe its time
variability, and find that the polarimetric responses of the Arecibo
Observatory's 1.4 and 2.1 GHz receivers vary significantly with time.Comment: 41 pages, 20 figure
Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set
When galaxies merge, the supermassive black holes in their centers may form
binaries and, during the process of merger, emit low-frequency gravitational
radiation in the process. In this paper we consider the galaxy 3C66B, which was
used as the target of the first multi-messenger search for gravitational waves.
Due to the observed periodicities present in the photometric and astrometric
data of the source of the source, it has been theorized to contain a
supermassive black hole binary. Its apparent 1.05-year orbital period would
place the gravitational wave emission directly in the pulsar timing band. Since
the first pulsar timing array study of 3C66B, revised models of the source have
been published, and timing array sensitivities and techniques have improved
dramatically. With these advances, we further constrain the chirp mass of the
potential supermassive black hole binary in 3C66B to less than using data from the NANOGrav 11-year data set. This
upper limit provides a factor of 1.6 improvement over previous limits, and a
factor of 4.3 over the first search done. Nevertheless, the most recent orbital
model for the source is still consistent with our limit from pulsar timing
array data. In addition, we are able to quantify the improvement made by the
inclusion of source properties gleaned from electromagnetic data to `blind'
pulsar timing array searches. With these methods, it is apparent that it is not
necessary to obtain exact a priori knowledge of the period of a binary to gain
meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap
Bayesian Solar Wind Modeling with Pulsar Timing Arrays
Using Bayesian analyses we study the solar electron density with the NANOGrav
11-year pulsar timing array (PTA) dataset. Our model of the solar wind is
incorporated into a global fit starting from pulse times-of-arrival. We
introduce new tools developed for this global fit, including analytic
expressions for solar electron column densities and open source models for the
solar wind that port into existing PTA software. We perform an ab initio
recovery of various solar wind model parameters. We then demonstrate the
richness of information about the solar electron density, , that can be
gleaned from PTA data, including higher order corrections to the simple
model associated with a free-streaming wind (which are informative probes of
coronal acceleration physics), quarterly binned measurements of and a
continuous time-varying model for spanning approximately one solar cycle
period. Finally, we discuss the importance of our model for chromatic noise
mitigation in gravitational-wave analyses of pulsar timing data and the
potential of developing synergies between sophisticated PTA solar electron
density models and those developed by the solar physics community.Comment: 22 pages, 7 figures, Submitted to Ap
The NANOGrav 12.5-Year Data Set: Polarimetry and Faraday Rotation Measures from Observations of Millisecond Pulsars with the Green Bank Telescope
In this work, we present polarization profiles for 23 millisecond pulsars
observed at 820 MHz and 1500 MHz with the Green Bank Telescope as part of the
NANOGrav pulsar timing array. We calibrate the data using Mueller matrix
solutions calculated from observations of PSRs B1929+10 and J1022+1001. We
discuss the polarization profiles, which can be used to constrain pulsar
emission geometry, and present both the first published radio polarization
profiles for nine pulsars and the discovery of very low intensity average
profile components ("microcomponents") in four pulsars. Using the Faraday
rotation measures, we measure for each pulsar and use it to calculate the
Galactic magnetic field parallel to the line of sight for different lines of
sight through the interstellar medium. We fit for linear and sinusoidal trends
in time in the dispersion measure and Galactic magnetic field and detect
magnetic field variations with a period of one year in some pulsars, but
overall find that the variations in these parameters are more consistent with a
stochastic origin.Comment: 35 pages, 21 figures. Accepted to Ap
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