The cost-effectiveness of the second-generation direct-acting antivirals (DAA) has received considerable attention; however, their effect on wider societal costs has remained relatively unexplored. The aim of this study was to investigate the effect the new drugs have on sick leave compared to older treatment paradigms. This retrospective study utilized Swedish registry data to identify three cohorts (a) patients treated with ribavirin and/or peginterferons (peg-IFN) during 2005-2011; (b) patients treated with the first generation of DAAs and ribavirin and/or peg-IFN 2011-2013; and (c) patients treated with the new generation of DAAs 2014-2018. Individual-level data on sick leave and early retirement were used to compare days away from work the year prior to the year following treatment initiation. A difference-in-difference model was estimated to test for differences between the cohorts adjusting for age and gender. Days away from work prior to treatment initiation was similar in the cohorts 106, 85 and 94 days in cohorts 1 to 3. After treatment initiation, the number of days away from worked increased in cohort one and two to 150 and 140 days, while it remained similar in cohort three (88 days). The monetary value of the avoided sick leave was 7000-10 000 €. In conclusion, patients treated with second-generation DAAs without peg-IFN had fewer days of sick leave in the year following treatment initiation compared to older treatments. Some caution is advised when interpreting the absolute figures due to potential heterogeneity between cohorts as they were treated at different points in time.This article introduces a hybrid governance perspective to disaster management. Hybrid governance refers to situations where state and non-state actors collectively provide key services. We argue that hybridity is often the norm rather than exception for disaster management, particularly in developing countries where the state is often weak and may be unable or unwilling to provide essential services. In these instances, risks are addressed by the state and non-state entities-from citizens and NGOs to customary authorities. Because of their important role in risk reduction, disrupting hybrid processes by attempting to bring them under the remit of the state may create rather than reduce risk. To make this argument, we first outline the key tenants of hybridity and their applicability to disasters before illustrating hybridity through three case studies of hybrid risk management in three cities in Africa, Freetown, Sierra Leone, Dar es Salaam, Tanzania, and Monrovia, Liberia. This article is protected by copyright. All rights reserved.Grapevine trunk diseases have devastating consequences on vineyards worldwide. SHP099 European wild grapevines (Vitis vinifera subs. sylvestris) from the last viable population in Germany along the Rhine river showed variable degrees of resistance against Neofusicoccum parvum (strain Bt-67), a fungus associated with Botryosphaeriaceae-related dieback. Representative genotypes from different subclades of this population were mapped with respect to their ability to induce wood necrosis, as well as their defence responses in a controlled inoculation system. The difference in colonization patterns could be confirmed by cryo-scanning electron microscopy, while there was no relationship between vessel diameter and infection success. Resistant lines accumulated more stilbenes, that were in addition significantly partitioned to nonglycosylated viniferin trimers. By contrast, the susceptible genotypes accumulated less stilbenes with a significantly higher proportion of glycosylated piceid. We suggest a model in which in the resistant genotypes phenylpropanoid metabolism is channelled rapidly and specifically to the bioactive stilbenes. Our study specifies a resistant chemotype against grapevines trunk diseases and paves a way to breed for resistance against grapevine Botryosphaeriaceae-related dieback.

Atrioventricular node (AVN) ablation combined with His bundle pacing is an effective strategy for permanent atrial fibrillation (AF) with rapid ventricular rate refractory to pharmacological therapy. We aimed to access the feasibility and efficiency of His bundle pacing and AVN ablation guided by three-dimensional (3-D) mapping system throughout the procedure.

Eighteen patients with permanent AF with refractory rate and symptoms were referred for His bundle pacing and AVN ablation guided by 3-D mapping (CARTO3). Electroanatomic 3-D mapping of the right atrium and right ventricle was performed by the ablation catheter with CARTO 3 system, followed by the visualization of the leads for implantation and AVN ablation.

Implantation of His bundle and ventricular leads and AVN ablation were achieved successfully with the help of 3-D mapping in 17 patients. Selective His bundle pacing was achieved in five patients (29.4%), and the other (70.6%) were nonselective His bundle pacing. The mean procedure duration was 99.4 ± 16.4 minutes. The mean fluoroscopy time was 7.0 ± 2.6 minutes. The time spent on His lead implantation was 6.1 ± 3.2 minutes. One patient experienced AVN ablation from left side under aortic valves due to no effect of ablation in right atrium.

His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN.

We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families.

The c.700G>A, [p.(Gly234Arg)], c.1327T>C [p.(Ser443Pro], c.1333G>A [p.(Gly445Arg)], c.1661A>C [p.(Tyr554Ser)] and c.1706T>C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia.