bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Outcome of Antiretroviral Treatment in Patients With and Without Concomitant Tuberculosis Receiving Health Center–Based Care—Results From a Prospective Cohort Study
Authors: Reepalu Anton , Balcha Taye Tolera , Sturegård Erik , Medstrand Patrik , Björkman Per
Published: October 2017

Background

In order to increase treatment coverage, antiretroviral treatment (ART) is provided through primary health care in low-income high-burden countries, where tuberculosis (TB) co-infection is common. We investigated the long-term outcome of health center–based ART, with regard to concomitant TB.

Methods

ART-naïve adults were included in a prospective cohort at Ethiopian health centers and followed for up to 4 years after starting ART. All participants were investigated for active TB at inclusion. The primary study outcomes were the impact of concomitant TB on all-cause mortality, loss to follow-up (LTFU), and lack of virological suppression (VS). Kaplan-Meier survival estimates and Cox proportional hazards models with multivariate adjustments were used.

Results

In total, 141/729 (19%) subjects had concomitant TB, 85% with bacteriological confirmation (median CD4 count TB, 169 cells/mm3; IQR, 99–265; non-TB, 194 cells/mm3; IQR, 122–275). During follow-up (median, 2.5 years), 60 (8%) died and 58 (8%) were LTFU. After ≥6 months of ART, 131/630 (21%) had lack of VS. Concomitant TB did not influence the rates of death, LTFU, or VS. Male gender and malnutrition were associated with higher risk of adverse outcomes. Regardless of TB co-infection status, even after 3 years of ART, two-thirds of participants had CD4 counts below 500 cells/mm3.

Conclusions

Concomitant TB did not impact treatment outcomes in adults investigated for active TB before starting ART at Ethiopian health centers. However, one-third of patients had unsatisfactory long-term treatment outcomes and immunologic recovery was slow, illustrating the need for new interventions to optimize ART programs.
Strangulation
Authors: Scannell Meredith , MacDonald Andrea E. , Foster Corrine
Published: October 2017

Patients who've been strangled are at risk for negative outcomes, both medical and psychological. Learn how to spot the signs and symptoms, and how best to care for these patients.
Hand hygiene
Authors: Perkins Amanda
Published: October 2017

The most important thing you can do for your patients
High Dynamic Range Bacterial Cell Detection in a Novel “Lab-In-A-Comb” for High-Throughput Antibiotic Susceptibility Testing of Clinical Urine Samples
Authors: Pivetal Jeremy , Woodward Martin J. , Reis Nuno M. , Edwards Alexander D.
Published: October 2017

Antibiotic resistance in urinary tract infection is a major global challenge, and improved cost-effective and rapid antibiotic susceptibility tests (AST) are urgently needed to inform correct antibiotic selection. Although microfluidic technology can miniaturise AST, the high dynamic range of pathogen density found in clinical urine samples makes direct testing of clinical samples – rather than testing colonies from overnight agar plates – extremely challenging. We evaluated for the first time how pathogen concentration in urine affects microfluidic AST using a novel microplate-compatible high-throughput microfluidic AST system termed “Lab-on-a-Comb”. When tested with clinicalE. coliisolates at standardised density, these devices gave identical antibiotic susceptibility profiles to standard disc diffusion and microtitre plate tests. Bacterial detection directly in synthetic urine spiked with clinicalE. coliUTI isolates was possible over a very large dynamic range of starting cell densities, from 103– 108CFU/mL which covers the range of pathogen cell densities found in patient urine. The lowest cell density where cell growth was reproducibly detected optically was 9.6x102CFU/mL, corresponding to one single CFU detected in a 1 μL microcapillary-an unprecedented level of sensitivity. Cell growth kinetics followed a simple Monod model with fast growth limited by the substrate availability and an estimated doubling time of 24.5 min, indicating optimalE. coligrowth conditions within these microfluidic devices. There was a trade-off between sensitivity and speed of detection, with 105CFU/mL detection possible within 2h, but 6h incubation required at 103CFU/mL.
Hey2restricts cardiac progenitor addition to the developing heart
Authors: Gibb Natalie , Lazic Savo , Deshwar Ashish R. , Yuan Xuefei , Wilson Michael D. , Scott Ian C.
Published: October 2017

A key event in vertebrate heart development is the timely addition of second heart field (SHF) progenitor cells to the poles of the heart tube. This accretion process must occur to the proper extent to prevent a spectrum of congenital heart defects (CHDs). However, the factors that regulate this critical process are poorly understood. Here we demonstrate that Hey2, a bHLH transcriptional repressor, restricts SHF progenitor accretion to the zebrafish heart.hey2expression demarcated a distinct domain within the cardiac progenitor population. In the absence of Hey2 function an increase in myocardial cell number and SHF progenitors was observed. We found that Hey2 limited proliferation of SHF-derived cardiomyocytes in a cell-autonomous manner, prior to heart tube formation, and further restricted the developmental window over which SHF progenitors were deployed to the heart. Taken together, our data suggests a role for Hey2 in controlling the proliferative capacity and cardiac contribution of late-differentiating cardiac progenitors.
Peripherally-induced regulatory T cells contribute to the control of autoimmune diabetes
Authors: Schuster Cornelia , Zhao Fangzhu , Kissler Stephan
Published: October 2017

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3+regulatory T cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3+Tregs is generated in the periphery (pTregs) from Foxp3-CD4+T cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobesed diabetic (NOD) mouse model for T1D. We generated NOD mice deficient for theFoxp3enhancer CNS1 involved in pTreg induction. We show that CNS1 knockout decreased the frequency of pTregs and increased the risk of diabetes. Our results show that pTregs fulfill an important non-redundant function in the prevention of beta cell autoimmunity that causes T1D.
Short Linear Motifs In Intrinsically Disordered Regions Modulate HOG Signaling Capacity
Authors: Strome Bob , Hsu Ian , Li Cheong Man Mitchell , Zarin Taraneh , Nguyen Ba Alex , Moses Alan M
Published: October 2017

The effort to characterize intrinsically disordered regions of signaling proteins is rapidly expanding. An important class of disordered interaction modules are ubiquitous and functionally diverse elements known as short linear motifs (SLiMs). To further examine the role of SLiMs in signal transduction, we used a previously devised bioinformatics method to predict evolutionarily conserved SLiMs within a well-characterized pathway in S. cerevisiae. Using a single cell, reporter-based flow cytometry assay in conjunction with a fluorescent reporter driven by a pathway-specific promoter, we quantitatively assessed pathway output via systematic deletions of individual motifs. We found that, when deleted, 34% (10/29) of predicted SLiMs displayed a significant decrease in pathway output, providing evidence that these motifs play a role in signal transduction. In addition, we show that perturbations of parameters in a previously published stochastic model of HOG signaling could reproduce the quantitative effects of 4 out of 7 mutations in previously unknown SLiMs. Our study suggests that, even in well-characterized pathways, large numbers of functional elements remain undiscovered, and that challenges remain for application of systems biology models to interpret the effects of mutations in signalling pathways.

One-sentence Summary

Mutations of short conserved elements in disordered regions have quantitative effects on a model signaling pathway.
Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex
Authors: Guan Wuqiang , Cao Jun-Wei , Liu Lin-Yun , Zhao Zhi-Hao , Fu Yinghui , Yu Yong-Chun
Published: October 2017

Eye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (SST-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening likely crucial for cortical maturation and function.
Transgenerational dynamics of rDNA copy number inDrosophilamale germline stem cells
Authors: Lu Kevin L. , Nelson Jonathan O. , Warsinger-Pepe Natalie , Yamashita Yukiko M.
Published: October 2017

rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in theDrosophilamale germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in animals that inherit reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.
Electrophysiological indices of anterior cingulate cortex function reveal changing levels of cognitive effort and reward valuation that sustain task performance
Authors: Umemoto Akina , Inzlicht Michael , Holroyd Clay B.
Published: October 2017

Successful execution of goal-directed behaviors often requires the deployment of cognitive control, which is thought to require cognitive effort. Recent theories have proposed that anterior cingulate cortex (ACC) regulates control levels by weighing the reward-related benefits of control against its effort-related costs. However, given that the sensations of cognitive effort and reward valuation are available only to introspection, this hypothesis is difficult to investigate empirically. We have proposed that two electrophysiological indices of ACC function, frontal midline theta and the reward positivity (RewP), provide objective measures of these functions. To investigate this issue, we recorded the electroencephalogram (EEG) from participants engaged in an extended, cognitively-demanding task. Participants performed a time estimation task for 2 hours in which they received reward and error feedback according to their task performance. We observed that the amplitude of the RewP, a feedback-locked component of the event related brain potential associated with reward processing, decreased with time-on-task. Conversely, frontal midline theta power, which consists of 4-8 Hz EEG oscillations associated with cognitive effort, increased with time-on-task. We also examined how these phenomena changed over time by conducting within-participant multi-level modeling analyses. Our results suggest that extended execution of a cognitively-demanding task is characterized by an early phase in which high control levels combine with strong reward valuation to foster rapid improvements in task performance, and a later phase in which high control levels counteract waning reward valuation to maintain stable task performance.
Hierarchy of transcriptomic specialization across human cortex captured by myelin map topography
Authors: Burt Joshua B. , Demirtaş Murat , Eckner William J. , Navejar Natasha M. , Ji Jie Lisa , Martin William J. , Bernacchia Alberto , Anticevic Alan , Murray John D.
Published: October 2017

Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet the microscale bases of specialization across human cortex are poorly understood. Cortical hierarchy is conventionally informed by invasive measurements of long-range projections, creating the need for a principled proxy measure of hierarchy in humans. Moreover, cortex exhibits marked interareal variation in patterns of gene expression, yet organizing principles of its transcriptional architecture remain unclear. We hypothesized that functional specialization of human cortical microcircuitry involves hierarchical gradients of gene expression. We found that a noninvasive neuroimaging measure, the MRI-derived myelin map, reliably indexes hierarchy and closely resembles the dominant pattern of transcriptomic variation across human cortex. We found strong hierarchical gradients in expression profiles of genes related to microcircuit function and neuropsychiatric disorders. Our findings suggest that hierarchy defines an axis shared by the transcriptomic and anatomical architectures of human cortex, and that hierarchical gradients of microscale properties contribute to macroscale specialization of cortical function.
Enhancer identification and activity evaluation in the red flour beetle,Tribolium castaneum
Authors: Lai Yi-Ting , Deem Kevin D. , Borràs-Castells Ferran , Sambrani Nagraj , Rudolf Heike , Suryamohan Kushal , El-Sherif Ezzat , Halfon Marc S. , McKay Daniel J. , Tomoyasu Yoshinori
Published: October 2017

Evolution ofcis-properties (such as enhancers) often plays an important role in the production of diverse morphology. However, a mechanistic understanding is often limited by the absence of methods to study enhancers in species outside of established model systems. Here, we sought to establish methods to identify and test enhancer activity in the red flour beetle,Tribolium castaneum. To identify possible enhancer regions, we first obtained genome-wide chromatin profiles from various tissues and stages ofTriboliumvia FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements)-sequencing. Comparison of these profiles revealed a distinct set of open chromatin regions in each tissue and stage. Second, we established the first reporter assay system that works in bothDrosophilaandTribolium, usingnubbinin the wing andhunchbackin the embryo as case studies. Together, these advances will be useful to study the evolution ofcis-language and morphological diversity inTriboliumand other insects.
Idiosyncratic genome degradation in a bacterial endosymbiont of periodical cicadas
Authors: Campbell Matthew A. , Łukasik Piotr , Simon Chris , McCutcheon John P.
Published: October 2017

When a free-living bacterium transitions to a host-beneficial endosymbiotic lifestyle, it almost invariably loses a large fraction of its genome [1, 2]. The resulting small genomes often become unusually stable in size, structure, and coding capacity [3-5].CandidatusHodgkinia cicadicola (Hodgkinia), a bacterial endosymbiont of cicadas, sometimes exemplifies this genomic stability. TheHodgkiniagenome has remained completely co-linear in some cicadas diverged by tens of millions of years [6, 7]. But in the long-lived periodical cicadaMagicicada tredecim, theHodgkiniagenome has split into dozens of tiny, gene-sparse genomic circles that sometimes reside in distinctHodgkiniacells [8]. Previous data suggested that otherMagicicadaspecies harbor similarly complexHodgkiniapopulations, but the timing, number of origins, and outcomes of the splitting process were unknown. Here, by sequencingHodgkiniametagenomes from the remaining sixMagicicadaspecies and two sister species, we show that allMagicicadaspecies harborHodgkiniapopulations of at least twenty genomic circles each. We find little synteny among the 256Hodgkiniacircles analyzed except between the most closely related species. Individual gene phylogenies show thatHodgkiniafirst split in the common ancestor ofMagicicadaand its closest known relatives, but that most splitting has occurred withinMagicicadaand has given rise to highly variableHodgkiniagene dosages between cicada species. These data show thatHodgkiniagenome degradation has proceeded down different paths in differentMagicicadaspecies, and support a model of genomic degradation that is stochastic in outcome and likely nonadaptive for the host. These patterns mirror the genomic instability seen in some mitochondria.
Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy
Authors: Mosby L. S. , Hundt N. , Young G. , Fineberg A. , Polin M. , Mayor S. , Kukura P. , Köster D. V.
Published: October 2017

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect, and image individual membrane attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as a function of ATP concentration, providing evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network.

Statement of Significance

Here, we show that interferometric scattering microscopy in combination with single particle tracking enables label-free, high contrast imaging of filament dynamics on surfaces, while distinguishing different species based on their mass. These results significantly broaden the available toolkit, and associated capabilities of researchers studying dynamics of biological machines at interfaces.
Cryptic phylogeographic history sheds light on the generation of species diversity in sky-island mountains
Authors: He Kai , Wan Tao , Koepfli Klaus-Peter , Jin Wei , Liu Shao-Ying , Jiang Xue-Long
Published: October 2017

Biodiversity hotspots should be given high priority for conservation under the situation of global climate change. The sky islands in southwestern China are characterized by extraordinarily high species diversity and are among one of the world’s top biodiversity hotspots. However, neither the actual species diversity in this region or mechanisms generating this diversity are well explored. Here, we report on the phylogeographic analysis of the long-tailed mole (Scaptonyx fusicaudus), a semi-fossorial mammal that inhabits the montane cool forests across the Chinese sky islands and is considered to represent one species divided into two subspecies. Analyses using DNA sequence data from one mitochondrial and six nuclear genes revealed that populations inhabiting different mountains exhibited exceptionally strong geographic structure. The lowlands and large rivers act as “soft” and “hard” barriers to dispersal, respectively, isolating evolutionary lineages for up to 11 million years. Our results suggest that the mountain ranges act as interglacial refugia buffering populations from climate fluctuations, further facilitating allopatric diversification. Strikingly, species delimitation analyses suggests that the long-tailed mole may comprise 18 operational taxonomic units and 17 putative species. Our results suggest that for low-vagility species, the complex topography of the Chinese sky islands has shaped genetic diversity and structure and promoted exceptional diversification through a combination of eco-environmental stability as well as geographic fragmentation. The patterns observed in S. fusicaudus may be representative for other cold- adapted species, reflecting the generation of mammalian faunal diversity in the sky-island mountains of southwestern China.
Temperature and Water Quality-Related Patterns in Sediment-AssociatedSymbiodiniumCommunities Impact Symbiont Uptake and Fitness of Juvenile Acroporid Corals
Authors: Quigley Kate M. , Bay Line K. , Willis Bette L.
Published: October 2017

The majority of corals acquire their photo-endosymbiontSymbiodiniumfrom environmental sources anew each generation. Despite the critical role that environmental availability ofSymbiodiniumplays in the potential for corals to acclimate and adapt to changing environments, little is known about the diversity of free-livingSymbiodiniumcommunities and how variation in these communities influences uptake andin hospitecommunities in juvenile corals. Here we characterizeSymbiodiniumcommunity diversity in sediment samples collected from eight reefs representing latitudinal and cross-shelf variation in water quality and temperature regimes. Sediment-associatedSymbiodiniumcommunities were then compared toin hospitecommunities acquired byA. tenuisandA. milleporajuveniles following 11 – 145 days of experimental exposure to sediments from each of the reefs. Communities associated with juveniles and sediments differed substantially, with sediments harbouring four times more unique OTUs than juveniles (1125 OTUs vs. 271). Moreover, only 10.6% of these OTUs were shared between juveniles and sediments, indicating selective uptake by acroporid juveniles. The diversity and abundance ofSymbiodiniumtypes differed among sediment samples from different temperature and water quality environments.Symbiodiniumcommunities acquired by juveniles also differed among the sediment treatments, despite juveniles having similar parentage. Moreover,Symbiodiniumcommunities displayed different rates of infection, mortality, and photochemical efficiencies. This study demonstrates that the biogeography of free-livingSymbiodiniumtypes found within sediment reservoirs follows patterns along latitudinal and water quality environmental gradients on the Great Barrier Reef. We also demonstrate a bipartite strategy forSymbiodiniumuptake by juvenile corals of two horizontally-transmitting acroporid species, whereby uptake is selective within the constraints of environmental availability.
Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours
Authors: Treur Jorien L. , Gibson Mark , Taylor Amy E , Rogers Peter J , Munafò Marcus R
Published: October 2017

Study Objectives:Higher caffeine consumption has been linked to poorer sleep and insomnia complaints. We investigated whether these observational associations are the result of genetic risk factors influencing both caffeine consumption and poorer sleep, and/or whether they reflect (possibly bidirectional) causal effects.Methods:Summary-level data were available from genome-wide association studies (GWAS) on caffeine consumption (n=91,462), sleep duration, and chronotype (i.e., being a ‘morning’ versus an ‘evening’ person) (both n=128,266), and insomnia complaints (n=113,006). Linkage disequilibrium (LD) score regression was used to calculate genetic correlations, reflecting the extent to which genetic variants influencing caffeine consumption and sleep behaviours overlap. Causal effects were tested with bidirectional, two-sample Mendelian randomization (MR), an instrumental variable approach that utilizes genetic variants robustly associated with an exposure variable as an instrument to test causal effects. Estimates from individual genetic variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods.Results:There was no clear evidence for genetic correlation between caffeine consumption and sleep duration (rg=0.000,p=0.998), chronotype (rg=0.086,p=0.192) or insomnia (rg=-0.034,p=0.700). Two-sample Mendelian randomization analyses did not support causal effects from caffeine consumption to sleep behaviours, or the other way around.Conclusions:We found no evidence in support of genetic correlation or causal effects between caffeine consumption and sleep. While caffeine may have acute effects on sleep when taken shortly before habitual bedtime, our findings suggest that a more sustained pattern of high caffeine consumption is likely associated with poorer sleep through shared environmental factors.
A strategy to exploit surrogate sire technology in livestock breeding programs
Authors: Gottardo Paolo , Gorjanc Gregor , Battagin Mara , Gaynor R Chris , Jenko Janez , Ros-Freixedes Roger , Whitelaw C Bruce A , Mileham Alan J , Herring William O , Hickey John M
Published: October 2017

In this work, we performed simulations to develop and test a strategy for exploiting surrogate sire technology in animal breeding programs. Surrogate sire technology allows the creation of males that lack their own germline cells, but have transplanted spermatogonial stem cells from donor males. With this technology, a single elite male donor could give rise to huge numbers of progeny, potentially as much as all the production animals in a particular time period.

One hundred replicates of various scenarios were performed. Scenarios followed a common overall structure but differed in the strategy used to identify elite donors and how these donors were used in the product development part.

The results of this study showed that using surrogate sire technology would significantly increase the genetic merit of commercial sires, by as much as 6.5 to 9.2 years’ worth of genetic gain compared to a conventional breeding program. The simulations suggested that a strategy involving three stages (an initial genomic test followed by two subsequent progeny tests) was the most effective of all the strategies tested.

The use of one or a handful of elite donors to generate the production animals would be very different to current practice. While the results demonstrate the great potential of surrogate sire technology there are considerable risks but also other opportunities. Practical implementation of surrogate sire technology would need to account for these.
El Niño Southern Oscillation influences the abundance and movements of a marine top predator in coastal waters
Authors: Sprogis Kate R. , Christiansen Fredrik , Wandres Moritz , Bejder Lars
Published: October 2017

Large‐scale climate modes such as El Niño Southern Oscillation (ENSO) influence population dynamics in many species, including marine top predators. However, few quantitative studies have investigated the influence of large‐scale variability on resident marine top predator populations. We examined the effect of climate variability on the abundance and temporary emigration of a resident bottlenose dolphin (Tursiops aduncus) population off Bunbury, Western Australia (WA). This population has been studied intensively over six consecutive years (2007–2013), yielding a robust dataset that captures seasonal variations in both abundance and movement patterns. In WA, ENSO affects the strength of the Leeuwin Current (LC), the dominant oceanographic feature in the region. The strength and variability of the LC affects marine ecosystems and distribution of top predator prey. We investigated the relationship between dolphin abundance and ENSO, Southern Annular Mode, austral season, rainfall, sea surface salinity and sea surface temperature (SST). Linear models indicated that dolphin abundance was significantly affected by ENSO, and that the magnitude of the effect was dependent upon season. Dolphin abundance was lowest during winter 2009, when dolphins had high temporary emigration rates out of the study area. This coincided with the single El Niño event that occurred throughout the study period. Coupled with this event, there was a negative anomaly in SST and an above average rainfall. These conditions may have affected the distribution of dolphin prey, resulting in the temporary emigration of dolphins out of the study area in search of adequate prey. This study demonstrated the local effects of large‐scale climatic variations on the short‐term response of a resident, coastal delphinid species. With a projected global increase in frequency and intensity of extreme climatic events, resident marine top predators may not only have to contend with increasing coastal anthropogenic activities, but also have to adapt to large‐scale climatic changes.
Re‐evaluating pathogenicity of variants associated with the long QT syndrome
Authors: Kaltman Jonathan R. , Evans Frank , Fu Yi‐Ping
Published: October 2017

Introduction

Genetic testing for congenital long QT syndrome (LQTS) has become common. Recent studies have shown that some variants labelled as pathogenic might be misclassified due to sparse case reports and relatively common allele frequencies (AF) in the general population. This study aims to evaluate the presence of LQTS‐associated variants in the Genome Aggregation Database (gnomAD) population, and assess the functional impact of these variants.

Methods and results

Variants associated with LQTS from the Human Gene Mutation Database were extracted and matched to the gnomAD to evaluate population‐based AF. We used MetaSVM to predict the function of LQTS variants. Allele distribution by protein topology in KCNQ1, KCNH2, and SCN5A was compared between gnomAD (n = 123,136) and a cohort of LQTS patients aggregated from eight published studies (n = 2,683). Among the 1,415 LQTS‐associated single nucleotide variants in 30 genes, 347 (25%) are present in gnomAD; 24% of the 347 variants were predicted as functionally tolerated compared with 4% of variants not present in gnomAD (P < 0.001). Of the 347 pathogenic variants in gnomAD, seven (2%) had an AF of ≥ 0.001 and 65 (19%) variants had an AF of ≥ 0.0001. In KCNQ1, KCNH2, and SCN5A, allele distribution by protein functional region was significantly different with gnomAD alleles appearing less frequently in highly pathogenic domains than case alleles.

Conclusion

A significant number of LQTS variants have insufficient evidence for pathogenicity and relatively common AF in the general population. Caution should be used when ascribing pathogenicity to these variants.
Electrocardiographic features of failed and recurrent right ventricular outflow tract catheter ablation of idiopathic ventricular arrhythmias
Authors: Yamada Shinya , Chung Fa‐Po , Lin Yenn‐Jiang , Chang Shih‐Lin , Lo Li‐Wei , Hu Yu‐Feng , Tuan Ta‐Chuan , Chao Tze‐Fan , Liao Jo‐Nan , Lin Chung‐Hsing , Lin Chin‐Yu , Chang Yao‐Ting , Chang Ting‐Yung , Te Abigail Louise D. , Chen Shih‐Ann
Published: October 2017

Introduction

Various ECG algorithms have been proposed to identify the origin of idiopathic outflow tract (OT)‐ventricular arrhythmia (VA). However, electrocardiographic features of failed and recurrent right ventricular outflow tract (RVOT) ablation of idiopathic OT‐VAs have not been clearly elucidated.

Methods and results

A total of 264 consecutive patients (mean age: 44.0 ± 13.0 years, 96 male) undergoing RVOT ablation for OT‐VAs with a transition ≥V3, including 241 patients (91.6%) with initially successful procedures and 23 patients (8.4%) with failed ablation. Detailed clinical characteristics and ECG features were analyzed and compared between the two groups. VAs with failed RVOT ablation had larger peak deflection index (PDI), longer V2 R wave duration (V2Rd), smaller V2 S wave amplitude, higher R/S ratio in V2, higher V3 R wave amplitude, and larger V2 transition ratio than those with successful ablation. Multivariate analysis demonstrated that PDI, V2Rd, V2 transition ratio, and pacemapping score acquired during mapping independently predicted failed ablation (P  =  0.01, P  =  0.01, P  =  0.01, and P < 0.001, respectively). In 31 recurrent cases (12.8%) after initially successful ablation, multivariate Cox regression analysis showed that only the earliest activation time acquired during mapping predicted the recurrences after successful ablation (P  =  0.001). The recurrent cases displayed different ECG features comparing with those with failed ablation.

Conclusion

The electrocardiographic features of failed RVOT ablation of idiopathic OT‐VAs with a transition ≥V3 were characterized by PDI, V2Rd, V2 transition ratio, and pacemapping score acquired during mapping, unlike the recurrent RVOT ablation.
Usefulness of epicardial impedance evaluation for epicardial mapping and determination of epicardial ablation site for ventricular tachycardia: A pilot study
Authors: Kitamura Takeshi , Fukamizu Seiji , Miyazawa Satoshi , Kawamura Iwanari , Hojo Rintaro , Aoyama Yuya , Nishizaki Mitsuhiro , Sakurada Harumizu , Hiraoka Masayasu
Published: October 2017

Background

During epicardial mapping, determination of appropriate ablation sites in low voltage areas (LVA) is challenging because of large epicardial areas covered by adipose tissue.

Objective

To evaluate the impedance difference between epicardial fat and the epicardial LVA using multiple detector computed tomography (MDCT).

Methods

We enrolled patients who underwent ventricular tachycardia (VT) ablation via the epicardial approach after endocardial ablation failure. After the procedure, MDCT‐derived images of epicardial fat were loaded to the mapping system. Then, all points acquired during sinus rhythm were retrospectively superimposed and analyzed.

Results

This study included data from 7 patients (62.5 ± 3.9 years old) who underwent eight epicardial VT ablation procedures. After the procedure, MDCT‐derived images of epicardial fat were registered in eight procedures. Retrospective analysis of 1,595 mapping and 236 ablation points was performed. Of the 1,595 mapping points on the merged electroanatomical and epicardial fat maps, normal voltage area (NVA) and low voltage area (LVA) without fat had lower impedance than those with fat (NVA without fat 182 ± 46 Ω vs. NVA with fat 321 ± 164.0 Ω, P  =  0.001, LVA without fat 164 ± 69 Ω vs. LVA with fat 248 ± 89 Ω, P  =  0.002). Of the 236 ablation points, initial impedance before ablation was higher on epicardial fat than on epicardial LVA without fat (134 ± 16 Ω vs. 156 ± 28 Ω, P  =  0.01).

Conclusions

Real time epicardial impedance evaluation may be useful to determine effective epicardial ablation sites and avoid adipose tissue. However, the number of patients in the present study is limited. Further investigation with a large number of patients is needed to confirm our result.
Thermal latency adds to lesion depth after application of high‐power short‐duration radiofrequency energy: Results of a computer‐modeling study
Authors: Irastorza Ramiro M. , d'Avila Andre , Berjano Enrique
Published: October 2017

Introduction

The use of ultra‐short RF pulses could achieve greater lesion depth immediately after the application of the pulse due to thermal latency.

Methods and results

A computer model of irrigated‐catheter RF ablation was built to study the impact of thermal latency on the lesion depth. The results showed that the shorter the RF pulse duration (keeping energy constant), the greater the lesion depth during the cooling phase. For instance, after a 10‐second pulse, lesion depth grew from 2.05 mm at the end of the pulse to 2.39 mm (17%), while after an ultra‐short RF pulse of only 1 second the extra growth was 37% (from 2.22 to 3.05 mm). Importantly, short applications resulted in deeper lesions than long applications (3.05 mm vs. 2.39 mm, for 1‐ and 10‐second pulse, respectively). While shortening the pulse duration produced deeper lesions, the associated increase in applied voltage caused overheating in the tissue: temperatures around 100 °C were reached at a depth of 1 mm in the case of 1‐ and 5‐second pulses. However, since the lesion depth increased during the cooling period, lower values of applied voltage could be applied in short durations in order to obtain lesion depths similar to those in longer durations while avoiding overheating.

Conclusion

The thermal latency phenomenon seems to be the cause of significantly greater lesion depth after short‐duration high‐power RF pulses. Balancing the applied total energy when the voltage and duration are changed is not the optimal strategy since short pulses can also cause overheating.
The Impact of Blamer‐softening on Romantic Attachment in Emotionally Focused Couples Therapy
Authors: Burgess Moser Melissa , Johnson Susan M. , Dalgleish Tracy L. , Wiebe Stephanie A. , Tasca Giorgio A.
Published: October 2017

Emotionally Focused Couples Therapy (EFT; Johnson, ) treats relationship distress by targeting couples' relationship‐specific attachment insecurity. In this study, we used hierarchical linear modeling (Singer & Willett, ) to examine intercept and slope discontinuities in softened couples' trajectories of change in relationship satisfaction and relationship‐specific attachment over the course of therapy from a total sample of 32 couples. Softened couples (n = 16) reported a significant increase in relationship satisfaction and a significant decrease in attachment avoidance at the softening session. Although softened couples displayed an initial increase in relationship‐specific attachment anxiety at the softening session, their scores significantly decreased across post‐softening sessions. Results demonstrated the importance of the blamer‐softening change event in facilitating change in EFT.
Oral health of children and adolescents with mucopolysaccharidosis and mother's Sense of Coherence
Authors: Ruy Carneiro Natália Cristina , Duda Deps Tahyná , Campos França Esdras , Ribeiro Valadares Eugênia , Almeida Pordeus Isabela , Borges‐Oliveira Ana Cristina
Published: October 2017

Aims

The purpose of this study is assess the association between mother's Sense of Coherence (SOC) and the oral health status of children with and without mucopolysaccharidosis (MPS).

Methods

A cross‐sectional study was carried out with 29 children/adolescents with MPS and 29 children/adolescents without MPS, and their mothers in Brazil. Mothers completed the Antonovsky's SOC instrument (SOC‐13) and their children's oral cavity had been examined for developmental defects of enamel (DDE), occlusal problems, dental caries (DMFT/dmft) and oral hygiene. This study was approved by the Research Ethics Committee of the Universidade Federal de Minas Gerais.

Results

Mothers of children with MPS had lower SOC scores (mean: 33.3 [±4.0]) compared with mothers of children without MPS (mean: 36.9 [±4.5]) (p < 0.001). Mother's SOC of children with MPS were lower for those children with one or more decayed teeth (31.5 [±3.2]) than for those children/adolescents without caries (35.7 [±3.8]) (p = 0.004) and lower for those children/adolescents with one or more missing teeth (30.2 [±0.9]) than for those individuals identified without missing teeth (33.8 [±4.1]) (p = 0.046).

Conclusion

Mothers’ SOC of children/adolescents with MPS was associated with dental caries experience in their children. Improving mothers’ SOC should contribute to a better quality of life for their children.
Novel solution methods for initial boundary value problems of fractional order with conformable differentiation
Authors: Yavuz Mehmet
Published: October 2017

In this work, we develop a formulation for the approximate-analytical solution of fractional partial differential equations (PDEs) by using conformable fractional derivative. Firstly, we redefine the conformable fractional Adomian decomposition method (CFADM) and conformable fractional modified homotopy perturbation method (CFMHPM). Then, we solve some initial boundary value problems (IBVP) by using the proposed methods, which can analytically solve the fractional partial differential equations (FPDE). In order to show the efficiencies of these methods, we have compared the numerical and exact solutions of the IBVP. Also, we have found out that the proposed models are very efficient and powerful techniques in finding approximate solutions for the IBVP of fractional order in the conformable sense.
Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants
Authors: Oei Ju Lee , Finer Neil N , Saugstad Ola Didrik , Wright Ian M , Rabi Yacov , Tarnow-Mordi William , Rich Wade , Kapadia Vishal , Rook Denise , Smyth John P , Lui Kei , Vento Maximo
Published: October 2017

Objective

To determine the association between SpO2at 5 min and preterm infant outcomes.

Design

Data from 768 infants <32 weeks gestation from 8 randomised controlled trials (RCTs) of lower (≤0.3) versus higher (≥0.6) initial inspiratory fractions of oxygen (FiO2) for resuscitation, were examined.

Setting

Individual patient analysis of 8 RCTs

Interventions

Lower (≤0.3) versus higher (≥0.6) oxygen resuscitation strategies targeted to specific predefined SpO2before 10 min of age.

Patients

Infants <32 weeks gestation.

Main outcome measures

Relationship between SpO2at 5 min, death and intraventricular haemorrhage (IVH) >grade 3.

Results

5 min SpO2data were obtained from 706 (92%) infants. Only 159 (23%) infants met SpO2study targets and 323 (46%) did not reach SpO280%. Pooled data showed decreased likelihood of reaching SpO280% if resuscitation was initiated with FiO2<0.3 (OR 2.63, 95% CI 1.21 to 5.74, p<0.05). SpO2<80% was associated with lower heart rates (mean difference −8.37, 95% CI −15.73 to –1.01, *p<0.05) and after accounting for confounders, with IVH (OR 2.04, 95% CI 1.01 to 4.11, p<0.05). Bradycardia (heart rate <100 bpm) at 5 min increased risk of death (OR 4.57, 95% CI 1.62 to 13.98, p<0.05). Taking into account confounders including gestation, birth weight and 5 min bradycardia, risk of death was significantly increased with time taken to reach SpO280%.

Conclusion

Not reaching SpO280% at 5 min is associated with adverse outcomes, including IVH. Whether this is because of infant illness or the amount of oxygen that is administered during stabilisation is uncertain and needs to be examined in randomised trials
Chest compression during sustained inflation versus 3:1 chest compression:ventilation ratio during neonatal cardiopulmonary resuscitation: a randomised feasibility trial
Authors: Schmölzer Georg M , O Reilly Megan , Fray Caroline , van Os Sylvia , Cheung Po-Yin
Published: October 2017

Background

Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation.

Hypothesis

It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation.

Study design

Randomised feasibility trial.

Method

Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC.

Study interventions

Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the ‘3:1 group’ received CC using 3:1 C:V ratio until ROSC.

Primary outcome

Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011).

Conclusion

CC+SI is feasible in the delivery room.

Trial registration number

Clinicaltrials.gov NCT02083705, pre-results.
Effect of MRI on preterm infants and their families: a randomised trial with nested diagnostic and economic evaluation
Authors: Edwards A David , Redshaw Maggie E , Kennea Nigel , Rivero-Arias Oliver , Gonzales-Cinca Nuria , Nongena Phumza , Ederies Moegamad , Falconer Shona , Chew Andrew , Omar Omar , Hardy Pollyanna , Harvey Merryl Elizabeth , Eddama Oya , Hayward Naomi , Wurie Julia , Azzopardi Denis , Rutherford Mary A , Counsell Serena
Published: October 2017

Background

We tested the hypothesis that routine MRI would improve the care and well-being of preterm infants and their families.

Design

Parallel-group randomised trial (1.1 allocation; intention-to-treat) with nested diagnostic and cost evaluations (EudraCT 2009-011602-42).

Setting

Participants from 14 London hospitals, imaged at a single centre.

Patients

511 infants born before 33 weeks gestation underwent both MRI and ultrasound around term. 255 were randomly allocated (siblings together) to receive only MRI results and 255 only ultrasound from a paediatrician unaware of unallocated results; one withdrew before allocation.

Main outcome measures

Maternal anxiety, measured by the State-Trait Anxiety inventory (STAI) assessed in 206/214 mothers receiving MRI and 217/220 receiving ultrasound. Secondary outcomes included: prediction of neurodevelopment, health-related costs and quality of life.

Results

After MRI, STAI fell from 36.81 (95% CI 35.18 to 38.44) to 32.77 (95% CI 31.54 to 34.01), 31.87 (95% CI 30.63 to 33.12) and 31.82 (95% CI 30.65 to 33.00) at 14 days, 12 and 20 months, respectively. STAI fell less after ultrasound: from 37.59 (95% CI 36.00 to 39.18) to 33.97 (95% CI 32.78 to 35.17), 33.43 (95% CI 32.22 to 34.63) and 33.63 (95% CI 32.49 to 34.77), p=0.02. There were no differences in health-related quality of life. MRI predicted moderate or severe functional motor impairment at 20 months slightly better than ultrasound (area under the receiver operator characteristic curve (CI) 0.74; 0.66 to 0.83 vs 0.64; 0.56 to 0.72, p=0.01) but cost £315 (CI £295–£336) more per infant.

Conclusions

MRI increased costs and provided only modest benefits.

Trial registration

ClinicalTrials.gov NCT01049594https://clinicaltrials.gov/ct2/show/NCT01049594.

EudraCT: EudraCT: 2009-011602-42 (https://www.clinicaltrialsregister.eu/).