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Variceal Hemorrhage and Adverse Liver Outcomes in Patients With Cystic Fibrosis Cirrhosis

OBJECTIVES: Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver-related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis. METHODS: We determined 10-year incidence rates for VB, LT, LD, and all-cause mortality (ACM), and examined risk factors using competing risk models and Cox-proportional hazard regression. RESULTS: From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy-three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten-year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF-related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver. CONCLUSIONS: VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report

Introduction of a guideline for measurements of greenhouse gas fluxes from soils using non-steady-state chambers

Method Soils represent a major global source and sink of greenhouse gases (GHGs). Many studies of GHG fluxes between soil, plant and atmosphere rely on chamber measurements. Different chamber techniques have been developed over the last decades, each characterised by different requirements and limitations. In this manuscript, we focus on the non-steady-state technique which is widely used for manual measurements but also in automatic systems. Although the measurement method appears very simple, experience gained over the years shows that there are many details which have to be taken into account to obtain reliable measurement results. Aim This manuscript aims to share lessons learnt and pass on experiences in order to assist the reader with possible questions or unexpected challenges, ranging from the planning of the design of studies and chambers to the practical handling of the chambers and the quality assurance of the gas and data analysis. This concise introduction refers to a more extensive Best Practice Guideline initiated by the Working Group Soil Gases (AG Bodengase) of the German Soil Science Society (Deutsche Bodenkundliche Gesellschaft). The intention was to collect and aggregate the expertise of different working groups in the research field. As a compendium, this Best Practice Guideline is intended to help both beginners and experts to meet the practical and theoretical challenges of measuring soil gas fluxes with non-steady-state chamber systems and to improve the quality of the individual flux measurements and thus entire GHG studies by reducing sources of uncertainty and error

Emissionen von grundwasserbürtigem N2O in die Atmosphäre: Modellrechnungen zu einem 15N-Tracerversuch unter Feldbedingungen

In einem Tracerversuch mit isotopisch mar-kiertem Nitrat wurde unter Feldbedingungen (Gley-Podsol aus Talsand, darunter ein Lockergesteinsaquifer) die Denitrifikation im oberflächennahen Grundwasser und die daraus resultierende Emission von N2O in die Atmosphäre über einen Zeitraum von Juli bis September 2007 verfolgt. Die Messergebnisse dienten als Anfangs- und Randbedingungen und Vergleichswerte für Simulationsrechnungen zum Transport von N2O durch den Boden zur Atmosphäre mit einem numerischen Gasdiffusionsmodell. Die Ergebnisse der Simulationsrechnungen bestätigen, dass Diffusion der wesentliche Prozess für den N2O-Transport in dem untersuchten Boden war. Für die geringen grundwasserbürtigen N2O-Emissionen spielte N2O-Abbau im Boden keine Rolle. Wir schlussfolgern aus den Ergebnissen, dass die Simulationsrechnungen eine wertvolle Ergänzung zur experimentellen Datenbasis darstellen. Sie verdeutlichen u.a., dass die N2O-Emission am Versuchsstandort hauptsächlich durch N2O-Umsetzungen im Oberboden gesteuert wurde

Photometric redshifts from reconstructed QSO templates

From SDSS commissioning photometric and spectroscopic data, we investigate the utility of photometric redshift techniques to the task of estimating QSO redshifts. We consider empirical methods (e.g. nearest-neighbor searches and polynomial fitting), standard spectral template fitting and hybrid approaches (i.e. training spectral templates from spectroscopic and photometric observations of QSOs). We find that in all cases, due to the presence of strong emission-lines within the QSO spectra, the nearest-neighbor and template fitting methods are superior to the polynomial fitting approach. Applying a novel reconstruction technique, we can, from the SDSS multicolor photometry, reconstruct a statistical representation of the underlying SEDs of the SDSS QSOs. Although, the reconstructed templates are based on only broadband photometry the common emission lines present within the QSO spectra can be recovered in the resulting spectral energy distributions. The technique should be useful in searching for spectral differences among QSOs at a given redshift, in searching for spectral evolution of QSOs, in comparing photometric redshifts for objects beyond the SDSS spectroscopic sample with those in the well calibrated photometric redshifts for objects brighter than 20th magnitude and in searching for systematic and time variable effects in the SDSS broad band photometric and spectral photometric calibrations.Comment: 21 pages, 9 figures, LaTeX AASTeX, submitted to A

Baseline ultrasound and clinical correlates in children with cystic fibrosis.

Objective: To investigate the relationship between abdominal ultrasound (US) findings and demographic, historical and clinical features in children with CF. Study design: Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multi-center study of US to predict hepatic fibrosis. Consensus US patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and U.S. or Toronto CF registries. Chi-square or ANOVA were used to compare variables among US groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal US. Results: Findings in 719 subjects were normal (n=590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (p=0.0004), homogeneous (p<0.0001) and heterogeneous (p=0.03) were older than normal. More males were heterogeneous (p=0.001). More heterogeneous (15.0%, p=0.009) and cirrhosis (25.0%, p=0.005) ha

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PURPOSE: The number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. METHODS: The XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine-Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). CONCLUSIONS: Single-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

IMPORTANCE The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. OBJECTIVE To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. DESIGN, SETTING, AND PARTICIPANTS The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. INTERVENTIONS All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. MAIN OUTCOMES AND MEASURES The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. RESULTS Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). CONCLUSIONS AND RELEVANCE In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone

Detecting the warm-hot intergalactic medium through X-ray absorption lines

The warm-hot intergalactic medium (WHIM) at temperatures 1E5-1E7 K is believed to contain 30-50% of the baryons in the local universe. However, all current X-ray detections of the WHIM at redshifts z>0 are of low statistical significance (<=3sigma) and/or controversial. In this work, we aim to establish the detection limits of current X-ray observatories and explore requirements for next-generation X-ray telescopes for studying the WHIM through X-ray absorption lines. We analyze all available grating observations of Mrk 421 and obtain spectra with signal-to-noise ratio (S/N) of \sim90 and 190 per 50 mA spectral bin from Chandra and XMM observations, respectively. Although these spectra are two of the best ever collected with Chandra and XMM, we cannot confirm the two WHIM systems reported by Nicastro et al. in 2005. Our bootstrap simulations indicate that spectra with such high S/N cannot constrain the WHIM with OVII column densities N(OVII)\sim1e15 cm^{-2} (corresponding to an equivalent widths of 2.5 mA for a Doppler velocity of 50 km s^{-1}) at >=3sigma significance level. The simulation results also suggest that it would take >60 Ms for Chandra and 140 Ms for XMM to measure the N(OVII) at >=4sigma from a spectrum of a background QSO with flux of \sim0.2 mCrab (1 Crab = 2E-8 erg s^{-1} cm^{-2} at 0.5-2 keV). Future X-ray pectrographs need to be equipped with spectral resolution R \sim 4000 and effective area A>=100 cm^2 to accomplish the similar constraints with an exposure time of \sim2 Ms and would require \sim11 Ms to survey the 15 QSOs with flux \sim0.2 mCrab along which clear intergalactic OVI absorbers have been detected.Comment: 13 pages with 9 figures and 2 tables, accepted for publication in Ap