A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation?

Implantable cardioverter defibrillator (ICD) implantation carries a significant risk of complications, however published estimates appear inconsistent. We aimed to present a contemporary systematic review using meta-analysis methods of ICD complications in randomised controlled trials (RCTs) and compare it to recent data from the largest international ICD registry, the US National Cardiovascular Data Registry (NCDR). PubMed was searched for any RCTs involving ICD implantation published 1999-2013; 18 were identified for analysis including 6433 patients, mean follow-up 3 months-5.6 years. Exclusion criteria were studies of children, hypertrophic cardiomyopathy, congenital heart disease, resynchronisation therapy and generator changes. Total pooled complication rate from the RCTs (excluding inappropriate shocks) was 9.1%, including displacement 3.1%, pneumothorax 1.1% and haematoma 1.2%. Infection rate was 1.5%.There were no predictors of complications but longer follow-up showed a trend to higher complication rates (p=0.07). In contrast, data from the NCDR ICD, reporting on 356 515 implants (2006-2010) showed a statistically significant threefold lower total major complication rate of 3.08% with lead displacement 1.02%, haematoma 0.86% and pneumothorax 0.44%. The overall ICD complication rate in our meta-analysis is 9.1% over 16 months. The ICD complication reported in the NCDR ICD registry is significantly lower despite a similar population. This may reflect under-reporting of complications in registries. Reporting of ICD complications in RCTs and registries is very variable and there is a need to standardise classification of complications internationally

Function and anatomy of plant siRNA pools derived from hairpin transgenes

<p>Abstract</p> <p>Background</p> <p>RNA interference results in specific gene silencing by small-interfering RNAs (siRNAs). Synthetic siRNAs provide a powerful tool for manipulating gene expression but high cost suggests that novel siRNA production methods are desirable. Strong evolutionary conservation of siRNA structure suggested that siRNAs will retain cross-species function and that transgenic plants expressing heterologous siRNAs might serve as useful siRNA bioreactors. Here we report a detailed evaluation of the above proposition and present evidence regarding structural features of siRNAs extracted from plants.</p> <p>Results</p> <p>Testing the gene silencing capacity of plant-derived siRNAs in mammalian cells proved to be very challenging and required partial siRNA purification and design of a highly sensitive assay. Using the above assay we found that plant-derived siRNAs are ineffective for gene silencing in mammalian cells. Plant-derived siRNAs are almost exclusively double-stranded and most likely comprise a mixture of bona fide siRNAs and aberrant partially complementary duplexes. We also provide indirect evidence that plant-derived siRNAs may contain a hitherto undetected physiological modification, distinct from 3' terminal 2-O-methylation.</p> <p>Conclusion</p> <p>siRNAs produced from plant hairpin transgenes and extracted from plants are ineffective for gene silencing in mammalian cells. Thus our findings establish that a previous claim that transgenic plants offer a cost-effective, scalable and sustainable source of siRNAs is unwarranted. Our results also indicate that the presence of aberrant siRNA duplexes and possibly a plant-specific siRNA modification, compromises the gene silencing capacity of plant-derived siRNAs in mammalian cells.</p

Recent climate-driven ecological changes in tropical montane lakes of Rwenzori Mountains National Park, central Africa

Rwenzori Mountains National Park, which straddles the border between the Democratic Republic of Congo and Uganda, has experienced rapid glacier loss since the beginning of the twentieth century, yet there has been little investigation of aquatic biodiversity change in the park. This study presents a paleolimnological analysis from Lake Mahoma (2990 m asl), which is situated in the bamboo-forest transition zone. Diatom and organic geochemistry data from a 39-cm-long sediment core with a basal age of c. 1715 CE were compared with new analyses of previously published data from Lakes Bujuku (3891 m asl) and Lower Kitandara (3989 m asl), in the alpine zone. Comparisons were made to determine if aquatic ecosystem changes exhibited similar inter-lake patterns over the past ~ 150 years of climate warming and glacial recession, or if only local change was apparent. The diatom flora of Lake Mahoma is acidophilous, dominated by Aulacoseira ikapoënsis since at least the mid eighteenth century. In recent decades, the obligate nitrogen-heterotroph Nitzschia palea increased in importance, concurrent with declining δ15Norg values. We suggest that these late twentieth century changes were linked to regional warming and increased thermal stratification of Lake Mahoma. Regional comparisons of the Rwenzori lakes were done using existing organic geochemistry records (total organic carbon, C/N and δ13Corg) and through diatom compositional turnover analyses, and categorisation of species into one of four diatom growth morphology traits, or guilds: tychoplanktonic, high-profile, low-profile and motile. Over the past 150 years, all three lakes showed unidirectional, compositional diatom turnover, indicating that deterministic processes had affected diatom communities. Declining turnover at each site is broadly mirrored by an increase in tychoplanktonic taxa, along with concomitant declines in high-profile diatoms at Lake Mahoma, and low-profile diatoms at Lake Bujuku, and at least for the past 60 years, at Lower Kitandara. The interplay between diatom guilds at all sites is mainly a consequence of competition for available resources. Sediment organic carbon at all sites comes from both autochthonous and allochthonous sources, the relative abundances of which are influenced by the time elapsed since lakes had glaciers in their catchment

Decomposing firm-product appeal: How important is consumer taste? National Bank of Belgium Working Paper No. 337

We develop and structurally estimate a trade model in order to identify the importance of consumer taste. The model separates taste from quality and productivity (TFPQ) at the firm-product level. Export data by destination countries allow us to identify the level of taste from consumer heterogeneity across destinations. We decompose export revenue into the contribution of taste, quality and costs. We find that taste is very important and explains about 50 % of the variation in export revenue. Productivity (TFPQ) differences between firm-products become more prominent than taste in explaining export success only when the cost elasticity of improving quality is high

A survey of fungi at the University of Wisconsin-Waukesha Field Station

A long-term study of higher fungi and Myxomycetes, primarilyfrom the xeric oak woods, was started in 1978. Collections have been made periodically since then, and recent sampling in conifer plantations indicates that characteristic ectomycorrhizal species of Basidiomycetes are beginning to appear in these communities. To date seven Myxomy-cetes, 22 Ascomycetes, and 107 Basidiomycetes have been identifiedfrom various habitats. These data will be incorporated into a master list of fungi generated from long-term surveys at several additional sites in southeastern Wisconsin

How and When Service Beneficiaries' Gratitude Enriches Employees' Daily Lives

Conventional research on gratitude has focused on the benefits of expressing or experiencing gratitude for the individual. However, recent theory and research have highlighted that there may too be benefits associated with receiving others’ gratitude. Grounded in the Work–Home Resources model, we develop a conceptual model to understand whether, how, and for whom service providers (i.e., healthcare professionals) benefit from receiving service beneficiaries’ (i.e., patients) gratitude in their daily work. We hypothesize that perceived gratitude from service beneficiaries enhances service providers’ relational energy at work, which spills over to benefit their family lives later in the day. In addition, we hypothesize that the effect of gratitude on relational energy and its subsequent spillover effect to the family are contingent on employees’ occupational identity. Two experience sampling studies with data collected from healthcare professionals and their spouses for two consecutive weeks (each) provided support for our hypothesized model. We conclude by discussing the theoretical and practical implications of our work

Polygenic basis for adaptive morphological variation in a threatened Aotearoa | New Zealand bird, the hihi (Notiomystis cincta)

To predict if a threatened species can adapt to changing selective pressures, it is crucial to understand the genetic basis of adaptive traits, especially in species historically affected by severe bottlenecks. We estimated the heritability of three hihi (Notiomystis cincta) morphological traits known to be under selection: nestling tarsus length, body mass and head-bill length, using 523 individuals and 39,699 single nucleotide polymorphisms (SNPs) from a 50K Affymetrix SNP chip. We then examined the genetic architecture of the traits via chromosome partitioning analyses and genome-wide association scans (GWAS). Heritabilities estimated using pedigree relatedness or genomic relatedness were low. For tarsus length, the proportion of genetic variance explained by each chromosome was positively correlated with its size, and more than one chromosome explained significant variation for body mass and head-bill length. Finally, GWAS analyses suggested many loci of small effect contributing to trait variation for all three traits, although one locus (a SNP within an intron of the transcription factor HEY2) was tentatively associated with tarsus length. Our findings suggest a polygenic nature for the morphological traits, with many small effect size loci contributing to the majority of the variation, similar to results from many other wild populations. However, the small effective population size, polygenic architecture and already low heritabilities suggest that both the total response and rate of response to selection are likely to be limited in hihi

Fourier Growth of Structured ??-Polynomials and Applications

We analyze the Fourier growth, i.e. the L? Fourier weight at level k (denoted L_{1,k}), of various well-studied classes of "structured" m F?-polynomials. This study is motivated by applications in pseudorandomness, in particular recent results and conjectures due to [Chattopadhyay et al., 2019; Chattopadhyay et al., 2019; Eshan Chattopadhyay et al., 2020] which show that upper bounds on Fourier growth (even at level k = 2) give unconditional pseudorandom generators. Our main structural results on Fourier growth are as follows: - We show that any symmetric degree-d m F?-polynomial p has L_{1,k}(p) ? Pr [p = 1] ? O(d)^k. This quadratically strengthens an earlier bound that was implicit in [Omer Reingold et al., 2013]. - We show that any read-? degree-d m F?-polynomial p has L_{1,k}(p) ? Pr [p = 1] ? (k ? d)^{O(k)}. - We establish a composition theorem which gives L_{1,k} bounds on disjoint compositions of functions that are closed under restrictions and admit L_{1,k} bounds. Finally, we apply the above structural results to obtain new unconditional pseudorandom generators and new correlation bounds for various classes of m F?-polynomials

Prioritized Sweeping Neural DynaQ with Multiple Predecessors, and Hippocampal Replays

During sleep and awake rest, the hippocampus replays sequences of place cells that have been activated during prior experiences. These have been interpreted as a memory consolidation process, but recent results suggest a possible interpretation in terms of reinforcement learning. The Dyna reinforcement learning algorithms use off-line replays to improve learning. Under limited replay budget, a prioritized sweeping approach, which requires a model of the transitions to the predecessors, can be used to improve performance. We investigate whether such algorithms can explain the experimentally observed replays. We propose a neural network version of prioritized sweeping Q-learning, for which we developed a growing multiple expert algorithm, able to cope with multiple predecessors. The resulting architecture is able to improve the learning of simulated agents confronted to a navigation task. We predict that, in animals, learning the world model should occur during rest periods, and that the corresponding replays should be shuffled.Comment: Living Machines 2018 (Paris, France