Extracorporeal CO2 removal in hypercapnic patients who fail noni nvasive ventialtion and refuse endotracheal intubation. a case series

Noninvasive ventilation (NIV) represents the standard of care for patients with exacerbation of chronic obstructive pulmonary disease. However, NIV fails in almost 40% of the most severe forms of acute hypercapnic respiratory failure and patients must undergo endotracheal intubation and invasive ventilation. Such transition from NIV to invasive ventilation is associated to increased mortality. Under these circumstances, patients may express a clear intention not to be intubated

A multilevel study of social networks and collective reactions to organizational change

The purpose of this study is to examine the micro-level dynamics underlying macro-level associations between organizational change and its outcomes, focusing in particular on the role of networks in shaping individual reactions to change. Drawing upon multilevel research on situational and individual antecedents of change, we first argue that the magnitude of change at the unit level has a nonlinear effect on change recipients' tendency to resist change, which in turn influences their adaptive behaviors. We argue, further, that the attitudinal and structural composition of the professional networks in which change recipients are embedded account for differences in their adaptive behaviors. Finally, we argue that individual adaptivity coalesces at the collective, that is, unit level, and predicts the attainment of desired change goals. We find general support for our arguments in a longitudinal study using multi-source data on 170 physicians in 29 units of a large hospital that experienced a major restructuring intervention. Results confirm that multilevel mechanisms involving individuals and their social context fundamentally undergird macro-level outcomes of change. We discuss the theoretical and practical implications of bringing a network perspective to bear on issues of individual and collective reactions to organizational change

Dust attenuation law in JWST galaxies at z = 7-8

Attenuation curves in galaxies depend on dust chemical composition, content, and grain size distribution. Such parameters are related to intrinsic galaxy properties such as metallicity, star formation rate, and stellar age. Due to the lack of observational constraints at high redshift, dust empirical curves measured in the local Universe (e.g. Calzetti and SMC curves) have been employed to describe the dust attenuation at early epochs. We exploit the high sensitivity and spectral resolution of the JWST to constrain the dust attenuation curves in high-z galaxies. Our goals are to check whether dust attenuation curves evolve with redshift and quantify the dependence of the inferred galaxy properties on the assumed dust attenuation law. We develop a modified version of the SED fitting code BAGPIPES by including a detailed dust attenuation curve parametrization. Dust parameters are derived, along with galaxy properties, from the fit to the data from FUV to mm bands. Once applied to three star-forming galaxies at z = 7-8, we find that their attenuation curves differ from local templates. One out of three galaxies shows a characteristic MW bump, typically associated to the presence of small carbonaceous dust grains such as PAHs. This is one of the first evidences suggesting the presence of PAHs in early galaxies. Galaxy properties such as stellar mass and SFR inferred from SED fitting are strongly affected by the assumed attenuation curve, though the adopted star formation history also plays a major role. Our results highlight the importance of accounting for the potential diversity of dust attenuation laws when analyzing the properties of galaxies at the EoR, whose dust properties are still poorly understood. The application of our method to a larger sample of galaxies observed with JWST can provide us important insights into the properties of dust and galaxies in the early universe.Comment: 19 pages, 10 figure

Comparing the effects of combined numerical and visuospatial psychoeducational trainings conducted by curricular teachers and external trainers. Preliminary evidence across kindergarteners

The aim of this study was to verify the efficacy of two pencil-and-paper trainings empowering numerical and visuo-spatial abilities in Italian five-year-old kindergarteners. Specifically, the trainings were respectively carried out by the curricular teacher or by an external trainer. The former received a specific training in order to use the psychoeducational programmes with her pupils, whereas the latter received a specific education about the role of numerical and visuo-spatial abilities for school achievement and she was also trained to use psychoeducational trainings in kindergarten schools. At pre-test and post-test nonverbal functions and numeracy knowledge were assessed through a battery of standardized tests. The results show that both the numerical psychoeducational programme and the visuo-spatial one are useful tools to enhance mathematical achievements in kindergarteners. However, when the trainings were proposed by the external trainer, the efficacy of the psychoeducational programmes was more significant. These outcomes seem to be related both to the expertise and the novelty effect of the external trainer on the classroom

Why we need continuous pharmaceutical manufacturing and how to make it happen : a summary of thoughts from the international symposium on continuous manufacturing

We make the case for why continuous pharmaceutical manufacturing is essential, what the barriers are, and how to overcome them. To overcome them, government action is needed in terms of tax incentives or regulatory incentives that affect time

Skin rash and response to cetuximab treatment: a retrospective single-center analysis

Background: The standard of care for patients with recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) not susceptible for surgery or reirradiation is chemotherapy with 5-FU and cisplatin plus cetuximab. Skin rash (SR) is a common adverse event of cetuximab. In patients treated with cetuximab for colorectal cancer there is strong evidence of a better outcome in those who undergo moderate or high grade of SR, and some retrospective data seem to confirm this finding in HNSCC. We report our experience. Materials and methods: We retrospectively reviewed 107 patients treated with cetuximab for R/M HNSCC from January 2014 to December 2016. Patients were divided in two groups by the grade of SR (G0-1 and G2-4), conforming to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Progression-free survival (PFS) was computed as time of progression or death since the date of assessment of recurrent/metastatic disease. Overall response rate (ORR) was computed as the sum of partial and complete responses and evaluated according to RECIST 1.1. PFS and ORR were correlated to the grade of rash. Results: 67 patients were evaluable for PFS: among them PFS was significantly longer (p 0.0014) in those who underwent a G2-4 rash (9,3 months) vs G0-1 (4,9 months). Hazard Ratio was 2,445 (CI 1.412-4.232). 95 patients were evaluable for ORR: among them G0-1 group had 4,2%, while G2-4 group had 36,8% of ORR. Conclusions: Our results support data of literature on improved outcome according to the development of skin rash in HNSCC. SR might be considered a predictive marker of response in these patients; nonetheless further ad hoc studies would be interesting

Peculiarities in the structure - properties relationship of epoxy-silica hybrids with highly organic siloxane domains

Epoxy-silica hybrids were produced from a diglycidyl ether of bisphenol-A resin using Jeffamine 230 hardener with a two-step in situ generation of siloxane domains. The siloxane component was obtained by hydrolysis and condensation of a mixture of γ-glycidoxypropyl-trimethoxysilane and tetraethoxysilane, which was added to the epoxy resin after removal of the formed alcohols and water. The morphological structure of the hybrids was examined by TEM, SAXS and WAXS analysis, and confirmation of the identified co-continuity of the constitutive phases for nominal silica contents greater than 18%wt was obtained by TGA and DMA analysis. While the loss modulus was found to increase monotonically over the entire range of siloxane content, the glass transition temperature exhibited a stepwise increase upon reaching the conditions for phase co-continuity. Molecular dynamics simulations were used to produce model structures for silsequioxanes cage-like structures, as main constituents of the siloxane phase. The predicted interdomain distance between the silsequioxane structures was in agreement with the SAXS experimental data

Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study

PURPOSE: Ventricular–arterial (V–A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l−1), arterial dP/dtmax (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms−1), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg−1 min−1, p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V–A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock

A survey of high-z galaxies: serra simulations

We introduce SERRA, a suite of zoom-in high-resolution (1.2 ×104 M⊙, ≃ 25 pc at z = 7.7) cosmological simulations including non-equilibrium chemistry and on-the-fly radiative transfer. The outputs are post-processed to derive galaxy ultraviolet (UV) + far-infrared (FIR) continuum and emission line properties. Results are compared with available multiwavelength data to constrain the physical properties [e.g. star formation rates (SFRs), stellar/gas/dust mass, metallicity] of high-redshift 6 ≲ z ≲ 15 galaxies. This flagship paper focuses on the z = 7.7 sub-sample, including 202 galaxies with stellar mass 107 M⊙ ≲ M⊙ ≲ 5 ×1010 M⊙, and specific star formation rate ranging from sSFR ∼100 Gyr-1 in young, low-mass galaxies to ∼10 Gyr-1 for older, massive ones. At this redshift, SERRA galaxies are typically bursty, i.e. they are located abo v e the Schmidt-Kennicutt relation by a factor κs = 3.03+4.9-1.8, consistent with recent findings for [O III ] and [C II ] emitters at high z. They also show relatively large InfraRed eXcess (IRX = LFIR/LUV) values as a result of their compact/clumpy morphology effectively blocking the stellar UV luminosity. Note that this conclusion might be affected by insufficient spatial resolution at the molecular cloud level. We confirm that early galaxies lie on the standard [C II ] -SFR relation; their observed L[OIII]/L [CII] ≃ 1-10 ratios can be reproduced by a part of the SERRA galaxies without the need of a top-heavy initial mass function and/or anomalous C/O abundances. [O I] line intensities are similar to local ones, making ALMA high-z detections challenging but feasible ( ∼6 h for an SFR of 50 M⊙yr-1)

Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity

Purpose It is well known that interferon-alpha (IFN-alpha), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations.Methods A total of 113 HCV patients, subdivided at the time of the enrollment in naive group (n = 64) and in IFN-alpha group (n = 49) previously treated with pegylated interferon-alpha and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs.Results Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-alpha group (8/49, 16.3%), while no HT cases were found in the naive group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naive group and 4/49 (8.2%) to IFN-alpha group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naive group and 6/49 (12.2%) from IFN-alpha group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism.Conclusions This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs