Electronic stopping calculated using explicit phase shift factors

Predicting range profiles of low-energy (0.1–10 keV/amu) ions implanted in materials is a long-standing problem of considerable theoretical and practical interest. We combine here the best available method for treating the nuclear slowing down, namely a molecular-dynamics range calculation method, with a method based on density-functional theory to calculate electronic slowing down for each ion-target atom pair separately. Calculation of range profiles of technologically important dopants in Si shows that the method is of comparable accuracy to previous methods for B, P, and As implantation of Si, and clearly more accurate for Al implantation of Si.Peer reviewe

Towards a more explicit account of the transformation: Reply to comments on “An integrative review of the enjoyment of sadness associated with music”

Our integrative framework for explaining the enjoyment of sadness associated with music sparked a delightful number (13) of commentaries which challenge, stimulate, strengthen and shape the ideas we initially put forward. Here we organize our response around five central themes brought up by several commentators. These relate to questions about (a) the nature of sad music, (b) whether music can induce genuine sadness, (c) details of the transformation, (d) music as a technology for emotion regulation, and (e) broader implications and extensions.nonPeerReviewe

Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

Background: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. Patients and methods: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. Results: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P <0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P <0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P <0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). Conclusions: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3

Signal transducer and activator of transcription 5 (STAT5) plays a critical role in cytokine-induced survival of hematopoietic cells. One of the STAT5 target genes is pim-1, which encodes an oncogenic serine/threonine kinase. Here we demonstrate that Pim-1 inhibits STAT5-dependent transcription in cells responsive to interleukin-3, prolactin, or erythropoietin. Ectopic expression of Pim-1 in cytokine- dependent FDCP1 myeloid cells results in reduced tyrosine phosphorylation and DNA binding of STAT5, indicating that Pim-1 interferes already with the initial steps of STAT5 activation. However, the Pim-1 kinase does not directly phosphorylate or bind to STAT5. By contrast, Pim-1 interacts with suppressor of cytokine signaling 1 (SOCS1) and SOCS3 and potentiates their inhibitory effects on STAT5, most likely via phosphorylation-mediated stabilization of the SOCS proteins. Thus, both Pim and SOCS family proteins may be components of a negative feedback mechanism that allows STAT5 to attenuate its own activity. (C) 2004 by The American Society of Hematology

Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

AbstractThe fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly

Revealing sources of CH4 in a boreal upland forest

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Revealing sources of biological methane production in boreal upland forests

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Catheter-Directed Thrombolysis Versus Pharmacomechanical Thrombectomy for Upper Extremity Deep Venous Thrombosis : A Cost-Effectiveness Analysis

Background: Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT. Methods: From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis (TM) device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment. Results: The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P <0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 (sic) and 5,975 (sic) in the CDT and PMT groups, respectively [P <0.00001]). Conclusions: The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.Peer reviewe

Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses

To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those &#60;2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening