The prevalence of NAFLD is increasing globally and on a path to becoming the most frequent cause of chronic liver disease. Strategies for the prevention and treatment of NAFLD are urgently needed.
A ...6-month prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy of daily NRPT (commercially known as Basis, a combination of nicotinamide riboside and pterostilbene) supplementation in 111 adults with NAFLD. The study consisted of three arms: placebo, recommended daily dose of NRPT (NRPT 1×), and a double dose of NRPT (NRPT 2×). NRPT appeared safe and well tolerated. At the end of the study, no significant change was seen in the primary endpoint of hepatic fat fraction with respect to placebo. However, among prespecified secondary outcomes, a time-dependent decrease in the circulating levels of the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) was observed in the NRPT 1× group, and this decrease was significant with respect to placebo. Furthermore, a significant decrease in the circulating levels of the toxic lipid ceramide 14:0 was also observed in the NRPT 1× group versus placebo, and this decrease was associated with a decrease in ALT in individuals of this group. A dose-dependent effect was not observed with respect to ALT, GGT, or ceramide 14:0 in the NRPT 2× group.
This study demonstrates that NRPT at the recommended dose is safe and may hold promise in lowering markers of hepatic inflammation in patients with NAFLD.
Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16 320 ...patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of ≤5 × 109/L (odds ratio OR, 3.1; 95% confidence interval CI, 2.0-4.8) compared with platelet counts ≥81 × 109/L. Platelet counts between 6 × 109/L and 80 × 109/L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit ≤25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to ≤50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713.
•Laboratory parameters associated with increased bleeding were platelet counts ≤5 × 109/L, hematocrits ≤25%, INR >1.2, and aPTT >30 seconds.•Platelet and RBC transfusions on days with bleeding are often not sufficient to change bleeding outcomes on the following day.
BASS. XXI. The Data Release 2 Overview Koss, Michael J.; Trakhtenbrot, Benny; Ricci, Claudio ...
The Astrophysical journal. Supplement series,
07/2022, Letnik:
261, Številka:
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Journal Article
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Abstract The BAT AGN Spectroscopic Survey (BASS) is designed to provide a highly complete census of the key physical parameters of the supermassive black holes (SMBHs) that power local active ...galactic nuclei (AGNs) ( z ≲ 0.3), including their bolometric luminosity ( L bol ), black hole (BH) mass ( M BH ), accretion rates ( L bol / L Edd ), line-of-sight gas obscuration ( N H ), and the distinctive properties of their host galaxies (e.g., star formation rates, masses, and gas fractions). We present an overview of the second data release of BASS (DR2), an unprecedented spectroscopic AGN survey in spectral range, resolution, and sensitivity, including 1449 optical (∼3200 Å–1 μ m) and 233 near-IR (1–2.5 μ m) spectra for the brightest 858 ultrahard X-ray (14–195 keV) selected AGNs across the entire sky and essentially all levels of obscuration. This release provides a highly complete set of key measurements (emission-line measurements and central velocity dispersions), with 99.9% measured redshifts and 98% BH masses estimated (for unbeamed AGNs outside the Galactic plane). The BASS DR2 AGN sample represents a unique census of nearby powerful AGNs, spanning over 5 orders of magnitude in AGN bolometric luminosity ( L bol ∼ 10 40 –10 47 erg s −1 ), BH mass ( M BH ∼ 10 5 –10 10 M ⊙ ), Eddington ratio ( L bol / L Edd ≳ 10 −5 ), and obscuration ( N H ∼ 10 20 –10 25 cm −2 ). The public BASS DR2 sample and measurements can thus be used to answer fundamental questions about SMBH growth and its links to host galaxy evolution and feedback in the local universe, as well as open questions concerning SMBH physics. Here we provide a brief overview of the survey strategy, the key BASS DR2 measurements, data sets and catalogs, and scientific highlights from a series of DR2-based works pursued by the BASS team.
Background: Real-world studies evaluating patients with challenging-to-treat localizations of psoriasis (scalp, nail, and palmoplantar) are limited. Objective: To characterize patients with versus ...without psoriasis in challenging-to-treat areas seen in routine US clinical practice. Methods: This retrospective observational study included all adult patients with psoriasis enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 who initiated a biologic therapy at registry enrollment. Patients were stratified by the presence of scalp, nail, or palmoplantar psoriasis (nonmutually exclusive groups). Patient demographics, clinical characteristics, disease activity, and patient-reported outcome measures (pain, fatigue, itch, EuroQol visual analog scale EQ VAS, Dermatology Life Quality Index DLQI, and Work Productivity and Activity Impairment questionnaire WPAI) were assessed at registry enrollment and compared between patients with versus without each challenging-to-treat area using nonparametric Kruskal-Wallis tests for continuous variables and χ 2 or Fisher exact tests for categorical variables. Generalized linear regression models were used to estimate differences in disease activity and patient-reported outcomes between patients with versus without each challenging-to-treat area. Results: Among 2,042 patients with psoriasis (mean age ±SD, 49.6 ± 14.7 years; 51.5% male), 38.4% had psoriatic arthritis (PsA), 38.1% had scalp psoriasis, 16.0% had nail psoriasis, 10.9% had palmoplantar psoriasis, and 26.2% had a combination of ≥2 challenging-to-treat areas and PsA; only 34.2% had body plaque psoriasis without PsA or challenging-to-treat areas. Patients in all challenging-to-treat groups reported higher (mean 95% CI) itch (scalp, 58.01 57.62–58.40 vs. 54.35 53.99–54.72; nail, 56.42 56.02–56.81 vs. 55.59 55.20–55.97; palmoplantar, 60.22 59.86–60.59 vs. 55.15 54.79–55.54) and lower EQ VAS (scalp, 68.12 67.78–68.48 vs. 69.46 69.12–69.81; nail, 66.21 65.89–66.55 vs. 69.48 69.14–69.83; palmoplantar, 66.21 66.07–66.75 vs. 69.29 68.94–69.94) scores than those without the respective challenging-to-treat localization. Patients with nail or palmoplantar psoriasis reported higher pain, fatigue, and DLQI scores than those without. Higher proportions of patients with scalp or palmoplantar psoriasis reported work impairment compared with those without. Conclusion: Two-thirds of patients with psoriasis who initiated biologic therapy had PsA and/or ≥1 challenging-to-treat area. Patients with challenging-to-treat areas had worse patient-reported outcome scores than those without, indicating a significant burden of challenging-to-treat areas on patients’ quality of life.
Abstract In this study, we use the Swift/BAT AGN sample, which has received extensive multiwavelength follow-up analysis as a result of the BAT AGN Spectroscopic Survey, to develop a diagnostic for ...nuclear obscuration by examining the relationship between the line-of-sight column densities ( N H ), the 2–10 keV to 12 μ m luminosity ratio, and WISE mid-infrared colors. We demonstrate that heavily obscured AGNs tend to exhibit both preferentially “redder” mid-infrared colors and lower values of L X,Obs. / L 12 μ m than less obscured AGNs, and we derive expressions relating N H to the L X,Obs. / L 12 μ m and L 22 μ m / L 4.6 μ m luminosity ratios, as well as develop diagnostic criteria using these ratios. Our diagnostic regions yield samples that are ≳80% complete and ≳60% pure for AGNs with log( N H /cm −2 ) ≥ 24, as well as ≳85% pure for AGNs with log ( N H / cm − 2 ) ≳ 23.5 . We find that these diagnostics cannot be used to differentiate between optically star-forming galaxies and active galaxies. Further, mid-IR contributions from host galaxies that dominate the observed 12 μ m emission can lead to larger apparent X-ray deficits and redder mid-IR colors than the AGNs would intrinsically exhibit, though this effect helps to better separate less and more obscured AGNs. Finally, we test our diagnostics on two catalogs of AGNs and infrared galaxies, including the XMM-Newton XXL-N field, and we identify several known Compton-thick AGNs, as well as a handful of candidate heavily obscured AGNs based upon our proposed obscuration diagnostics.
High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection ...in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393.
•Overall, no benefit of granulocyte transfusion therapy was observed, but the power of the study was reduced due to low accrual.•Post hoc secondary analysis suggested that patients receiving higher doses tended to have better outcomes than those receiving lower ones.
The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment.
To develop a model to predict the 2-year risk of ...developing PsA among patients with PsO.
This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.
A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%).
PsA misclassification bias by dermatologists.
PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.
Abstract
We present a catalog of the millimeter-wave (mm-wave) continuum properties of 98 nearby (
z
< 0.05) active galactic nuclei (AGNs) selected from the 70 month Swift/BAT hard-X-ray catalog that ...have precisely determined X-ray spectral properties and subarcsecond-resolution Atacama Large Millimeter/submillimeter Array Band 6 (211–275 GHz) observations as of 2021 April. Due to the hard-X-ray (>10 keV) selection, the sample is nearly unbiased for obscured systems at least up to Compton-thick-level obscuration, and provides the largest number of AGNs with high-physical-resolution mm-wave data (≲100–200 pc). Our catalog reports emission peak coordinates, spectral indices, and peak fluxes and luminosities at 1.3 mm (230 GHz). Additionally, high-resolution mm-wave images are provided. Using the images and creating radial surface brightness profiles of mm-wave emission, we identify emission extending from the central sources and isolated blob-like emission. Flags indicating the presence of these emission features are tabulated. Among 90 AGNs with significant detections of nuclear emission, 37 AGNs (≈41%) appear to have both or one of extended or blob-like components. We, in particular, investigate AGNs that show well-resolved mm-wave components and find that these seem to have a variety of origins (i.e., a jet, radio lobes, a secondary AGN, stellar clusters, a narrow-line region, galaxy disk, active star formation regions, or AGN-driven outflows), and some components have currently unclear origins.
The primary goal for this study was to compare story generation and narrative retell performance in children who are hard of hearing (CHH) and hearing children. A secondary goal was to determine ...factors that influence narrative performance. Research on this topic is important because narrative language competency is an essential communication function.
Participants included 86 CHH and 53 seven-year-old hearing children who had completed a test battery composed of vocabulary, grammar, phonological processing, story generation, and narrative retell tasks. Coders who were blind to hearing status used a scoring rubric to judge the quality of narrative macrostructure in story generation and narrative retells. Data were analyzed using analysis of variance to determine group differences and correlational models to examine individual differences.
At 7 years of age, CHH demonstrated significant deficits in narrative macrostructure compared to hearing children, with larger delays in narrative retell than story generation. Vocabulary, grammar, and phonological memory acted as mediators in the relationship between hearing status and story generation; grammar acted as a mediator between hearing status and narrative retell. Auditory access variables accounted for a significant proportion of shared variance in story generation skills for CHH.
School-age CHH are at risk for delays in narrative production, particularly with retelling stories. The results of this study highlight a narrative coding approach and task procedures that are sensitive to differences in language levels and may be clinically useful for professionals working with early school-age children.
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