Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

Pulmonary Hypertension in Patients with Chronic Fibrosing Idiopathic Interstitial Pneumonias

Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p<0.001). Total lung capacity, NYHA class IV, and mixed-venous oxygen saturation were independent predictors of survival in patients with PH-IIP. Conclusions Patients with PH-IIP have a dismal prognosis. Our results suggest that pulmonary vasodilator therapy may be associated with short-term functional improvement in some of these patients but it is unclear whether this treatment affects survival

Wave attenuation over coastal salt marshes under storm surge conditions

Coastal communities around the world face increasing risk from flooding as a result of rising sea level, increasing storminess, and land subsidence1–2. Salt marshes can act as natural buffer zones, providing protection from waves during storms3–7. However, the effectiveness of marshes in protecting the coastline during extreme events when water levels are at a maximum and waves are highest is poorly understood8,9. Here, we experimentally assess wave dissipation under storm surge conditions in a 300-meter-long wave flume tank that contains a transplanted section of natural salt marsh. We find that the presence of marsh vegetation causes considerable wave attenuation, even when water levels and waves are highest. From a comparison with experiments without vegetation, we estimate that up to 60% of observed wave reduction is attributed to vegetation. We also find that although waves progressively flatten and break vegetation stems and thereby reduce dissipation, the marsh substrate remained stable and resistant to surface erosion under all conditions. The effectiveness of storm wave dissipation and the resilience of tidal marshes even at extreme conditions suggests that salt marsh ecosystems can be a valuable component of coastal protection schemes.This is the author's accepted manuscript and will be under embargo until the 29th of March 2015. The final version has been published by NPG in Nature Geoscience here: http://www.nature.com/ngeo/journal/v7/n10/full/ngeo2251.html

Inguinal hernia surgery in the Netherlands: are patients treated according to the guidelines?

Purpose In 2003, a dedicated Dutch committee developed vidence-based guidelines for the treatment of nguinal hernia (IH) in children and adults. The aim of this tudy was to describe trends in hernia care before and after he publication of the guidelines on IH surgery in the etherlands. ethods Originally, a retrospective baseline analysis of H surgery in 90 Dutch hospitals was performed among atients treated for IH in 2001. The results of this baseline nalysis were compared with a recently performed second nalysis of patients treated for IH in 2005. esults In children\\4 years of age, the study showed a ignificant decrease of contralateral explorations. In adults, he study showed that significantly more patients were reated with a mesh-based repair in 2005 (95.9 vs. 78.8%, <0.01eover, there was an increase of patients ith bilateral hernia treated with an endoscopic technique 41.5 vs. 22.3%, P<0.01) and more patients were treated n day surgery (53.5 vs. 38.6%, P<0.01). Lastly, a decline n operations performed for recurrent IH in adults was bserved (10.9 vs. 13.3%, P<0.01). onclusion This study showed that most patients with IH n the Netherlands were treated according to the main ecommendations of the Dutch evidence-based guidelines

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Long-time Low-latency Quantum Memory by Dynamical Decoupling

Quantum memory is a central component for quantum information processing devices, and will be required to provide high-fidelity storage of arbitrary states, long storage times and small access latencies. Despite growing interest in applying physical-layer error-suppression strategies to boost fidelities, it has not previously been possible to meet such competing demands with a single approach. Here we use an experimentally validated theoretical framework to identify periodic repetition of a high-order dynamical decoupling sequence as a systematic strategy to meet these challenges. We provide analytic bounds-validated by numerical calculations-on the characteristics of the relevant control sequences and show that a "stroboscopic saturation" of coherence, or coherence plateau, can be engineered, even in the presence of experimental imperfection. This permits high-fidelity storage for times that can be exceptionally long, meaning that our device-independent results should prove instrumental in producing practically useful quantum technologies.Comment: abstract and authors list fixe

Internet-based treatment for PTSD reduces distress and facilitates the development of a strong therapeutic alliance: a randomized controlled clinical trial

BACKGROUND: The present study was designed to evaluate the efficacy of an internet-based therapy (Interapy) for Posttraumatic Stress Disorder (PTSD) in a German speaking population. Also, the quality of the online therapeutic relationship, its development and its relevance as potential moderator of the treatment effects was investigated. METHOD: Ninety-six patients with posttraumatic stress reactions were allocated at random to ten sessions of Internet-based cognitive behavioural therapy (CBT) conducted over a 5-week period or a waiting list control group. Severity of PTSD was the primary outcome. Secondary outcome variables were depression, anxiety, dissociation and physical health. Follow-up assessments were conducted at the end of treatment and 3 months after treatment. RESULTS: From baseline to post-treatment assessment, PTSD severity and other psychopathological symptoms were significantly improved for the treatment group (intent-to-treat group x time interaction effect size d = 1.40). Additionally, patients of the treatment condition showed significantly greater reduction of co-morbid depression and anxiety as compared to the waiting list condition. These effects were sustained during the 3-months follow-up period. High ratings of the therapeutic alliance and low drop-out rates indicated that a positive and stable therapeutic relationship could be established online. Significant improvement of the online working alliance in the course of treatment and a substantial correlation between the quality of the online relationship at the end of treatment and treatment outcome emerged. CONCLUSION: Interapy proved to be a viable treatment alternative for PTSD with large effect sizes and sustained treatment effects. A stable and positive online therapeutic relationship can be established through the Internet which improved during the treatment process. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN012606000401550

"I am your mother and your father!": In vitro derived gametes and the ethics of solo reproduction

In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes

Imaging-guided chest biopsies: techniques and clinical results

Background This article aims to comprehensively describe indications, contraindications, technical aspects, diagnostic accuracy and complications of percutaneous lung biopsy. Methods Imaging-guided biopsy currently represents one of the predominant methods for obtaining tissue specimens in patients with lung nodules; in many cases treatment protocols are based on histological information; thus, biopsy is frequently performed, when technically feasible, or in case other techniques (such as bronchoscopy with lavage) are inconclusive. Results Although a coaxial system is suitable in any case, two categories of needles can be used: fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB), with the latter demonstrated to have a slightly higher overall sensitivity, specificity and accuracy. Conclusion Percutaneous lung biopsy is a safe procedure even though a few complications are possible: pneumothorax, pulmonary haemorrhage and haemoptysis are common complications, while air embolism and seeding are rare, but potentially fatal complications