The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation

Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection

What happens in the Lab: Applying Midstream Modulation to Enhance Critical Reflection in the Laboratory

In response to widespread policy prescriptions for responsible innovation, social scientists and engineering ethicists, among others, have sought to engage natural scientists and engineers at the ‘midstream’: building interdisciplinary collaborations to integrate social and ethical considerations with research and development processes. Two ‘laboratory engagement studies’ have explored how applying the framework of midstream modulation could enhance the reflections of natural scientists on the socio-ethical context of their work. The results of these interdisciplinary collaborations confirm the utility of midstream modulation in encouraging both first- and second-order reflective learning. The potential for second-order reflective learning, in which underlying value systems become the object of reflection, is particularly significant with respect to addressing social responsibility in research practices. Midstream modulation served to render the socio-ethical context of research visible in the laboratory and helped enable research participants to more critically reflect on this broader context. While lab-based collaborations would benefit from being carried out in concert with activities at institutional and policy levels, midstream modulation could prove a valuable asset in the toolbox of interdisciplinary methods aimed at responsible innovation

BEATVIC, a body-oriented resilience therapy using kickboxing exercises for people with a psychotic disorder:a feasibility study

BACKGROUND: People with a psychotic disorder have an increased risk of becoming the victim of a crime. To prevent victimization a body-oriented resilience therapy using kickboxing exercises was developed. This study aims to explore the feasibility of the therapy, to improve the therapy protocol and to explore suitable outcomes for a RCT. METHODS: Twenty-four adults with a psychotic disorder received 20 weekly group sessions in which potential risk factors for victimization and strategies for dealing with them were addressed. Sessions were evaluated weekly. During pre and post assessment participants completed questionnaires on, among other, victimization, aggression regulation and social functioning. RESULTS: The short recruitment period indicates the interest in such an intervention and the willingness of clients to participate. Mean attendance was 85.3 and 88% of the participants completed fifteen or more sessions. The therapy protocol was assessed as adequate and exercises as relevant with some small improvements to be made. The victimization and aggression regulation questionnaires were found to be suitable outcome measurements for a subsequent RCT. CONCLUSION: The results support the feasibility of the BEATVIC therapy. Participants subjectively evaluated the intervention as helpful in their attempt to gain more self-esteem and assertiveness. With some minor changes in the protocol the effects of BEATVIC can be tested in a RCT. TRIAL REGISTRATION: The trial registration number (TRN) is 35949 (date submitted 09/11/2018). Retrospectively registered

Specialist versus primary care prostate cancer follow-up:A process evaluation of a randomized controlled trial

Background: A randomized controlled trial (RCT) is currently comparing the effectiveness of specialist- versus primary care-based prostate cancer follow-up. This process evaluation assesses the reach and identified constructs for the implementation of primary care-based follow-up. Methods: A mixed-methods approach is used to assess the reach and the implementation through the Consolidated Framework for Implementation Research. We use quantitative data to evaluate the reach of the RCT and qualitative data (interviews) to indicate the perspectives of patients (n = 15), general practitioners (GPs) (n = 10), and specialists (n = 8). Thematic analysis is used to analyze the interview transcripts. Results: In total, we reached 402 (67%) patients from 12 hospitals and randomized them to specialist- (n = 201) or to primary care-based (n = 201) follow-up. From the interviews, we identify several advantages of primary care- versus specialist-based follow-up: it is closer to home, more accessible, and the relationship is more personal. Nevertheless, participants also identified challenges: guidelines should be implemented, communication and collaboration between primary and secondary care should be improved, quality indicators should be collected, and GPs should be compensated. Conclusion: Within an RCT context, 402 (67%) patients and their GPs were willing to receive/provide primary care-based follow-up. If the RCT shows that primary care is equally as effective as specialist-based follow-up, the challenges identified in this study need to be addressed to enable a smooth transition of prostate cancer follow-up to primary care. Netherlands Trial Registry, Trial NL7068 (NTR7266)

Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids

Background: Pharmacotherapies for people with cystic fibrosis (pwCF) who have premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are under development. Thus far, clinical studies focused on compounds that induce translational readthrough (RT) at the mRNA PTC location. Recent studies using primary airway cells showed that PTC functional restoration can be achieved through combining compounds with multiple mode-of-actions. Here, we assessed induction of CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense mRNA mediated decay (NMD) and CFTR protein modulation. Methods: Rescue of PTC CFTR protein was assessed by forskolin-induced swelling of 12 intestinal organoid cultures carrying distinct PTC mutations. Effects of compounds on mRNA CFTR level was assessed by RT-qPCRs. Results: Whilst response varied between donors, significant rescue of CFTR function was achieved for most donors with the quintuple combination of a commercially available pharmacological equivalent of the RT compound (ELX-02-disulfate or ELX-02ds), NMD inhibitor SMG1i, correctors VX-445 and VX-661 and potentiator VX-770. The quintuple combination of pharmacotherapies reached swelling quantities higher than the mean swelling of three VX-809/VX-770-rescued F508del/F508del organoid cultures, indicating level of rescue is of clinical relevance as VX-770/VX-809-mediated F508del/F508del rescue in organoids correlate with substantial improvement of clinical outcome. Conclusions: Whilst variation in efficacy was observed between genotypes as well as within genotypes, the data suggests that strong pharmacological rescue of PTC requires a combination of drugs that target RT, NMD and protein function

Exciton Spin Dynamics in Semiconductor Quantum Wells

In this paper we will review Exciton Spin Dynamics in Semiconductor Quantum Wells. The spin properties of excitons in nanostructures are determined by their fine structure. We will mainly focus in this review on GaAs and InGaAs quantum wells which are model systems.Comment: 55 pages, 27 figure

Responsibility Ascriptions in Technology Development and Engineering: Three Perspectives

In the last decades increasing attention is paid to the topic of responsibility in technology development and engineering. The discussion of this topic is often guided by questions related to liability and blameworthiness. Recent discussions in engineering ethics call for a reconsideration of the traditional quest for responsibility. Rather than on alleged wrongdoing and blaming, the focus should shift to more socially responsible engineering, some authors argue. The present paper aims at exploring the different approaches to responsibility in order to see which one is most appropriate to apply to engineering and technology development. Using the example of the development of a new sewage water treatment technology, the paper shows how different approaches for ascribing responsibilities have different implications for engineering practice in general, and R&D or technological design in particular. It was found that there was a tension between the demands that follow from these different approaches, most notably between efficacy and fairness. Although the consequentialist approach with its efficacy criterion turned out to be most powerful, it was also shown that the fairness of responsibility ascriptions should somehow be taken into account. It is proposed to look for alternative, more procedural ways to approach the fairness of responsibility ascriptions

Osteoporosis and increased risk of fractures

Osteoporosis is a common condition in older people. This condition leads to increased risk of fractures and is associated with morbidity and mortality. The number of patients with osteoporosis will increase significantly in the years to come due to the increasing numbers of older people and increasing life expectancy. This will be accompanied by increasing demand for care and clinical practice will be faced with questions about therapeutic options and the optimal treatment duration for patients with osteoporosis or increased risk of fractures. In this educational article, we are using practical questions to provide an overview of pathophysiology, diagnostics and treatment of osteoporosis and increased risk of fractures

Search for magnetic monopoles in √s = 7 TeV pp collisions with the ATLAS detector

This Letter presents a search for magnetic monopoles with the ATLAS detector at the CERN Large Hadron Collider using an integrated luminosity of 2.0  fb−1 of pp collisions recorded at a center-of-mass energy of √s = 7 TeV. No event is found in the signal region, leading to an upper limit on the production cross section at 95% confidence level of 1.6/ϵ fb for Dirac magnetic monopoles with the minimum unit magnetic charge and with mass between 200 GeV and 1500 GeV, where ϵ is the monopole reconstruction efficiency. The efficiency ϵ is high and uniform in the fiducial region given by pseudorapidity |η|<1.37 and transverse kinetic energy 600-700<Ekinsinθ<1400 GeV. The minimum value of 700 GeV is for monopoles of mass 200 GeV, whereas the minimum value of 600 GeV is applicable for higher mass monopoles. Therefore, the upper limit on the production cross section at 95% confidence level is 2 fb in this fiducial region. Assuming the kinematic distributions from Drell-Yan pair production of spin-1/2 Dirac magnetic monopoles, the efficiency is in the range 1%-10%, leading to an upper limit on the cross section at 95% confidence level that varies from 145 fb to 16 fb for monopoles with mass between 200 GeV and 1200 GeV. This limit is weaker than the fiducial limit because most of these monopoles lie outside the fiducial region