bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comprehensive Evaluation of the Genetic Architecture of Sudden Cardiac Arrest
Authors: Ashar Foram N. , Mitchell Rebecca N. , Albert Christine M. , Newton-Cheh Christopher , Brody Jennifer A. , Muller-Nurasyid Martina , Moes Anna , Meitinger Thomas , Mak Angel , Huikuri Heikki , Junttila M. Juhani , Goyette Philippe , Pulit Sara L. , Pazoki Raha , Tanck Michael W. , Blom Marieke T. , Zhao XiaoQing , Hauvlinna Aki S. , Jabbari Reza , Glinge Charlotte , Tragante Vinicius , Escher Stefan A. , Chakravarti Aravinda , Ehret Georg , Coresh Josef , Li Man , Prineas Ronald J. , Franco Oscar H. , Kwok Pui-Yan , Lumley Thomas , Dumas Florence , McKnight Barbara , Rotter Jerome I. , Lemaitre Rozenn N. , Heckbert Susan R. , O’Donnell Christopher J. , Hwang Shih-Jen , Tardif Jean-Claude , Kortelainen Marja-Leena , VanDenburgh Martin , Uitterlinden Andre G. , Hofman Albert , Stricker Bruno H.C. , de Bakker Paul I.W. , Franks Paul W. , Jansson Jan-Hakan , Asselbergs Folkert W. , Halushka Marc K. , Maleszewski Joseph J. , Tfelt-Hansen Jacob , Engstrom Thomas , Salomaa Veikko , Virmani Renu , Kolodgie Frank , Wilde Arthur A.M. , Tan Hanno L. , Bezzina Connie R. , Eijgelsheim Mark , Rioux John D. , Jouven Xavier , Kaab Stefan , Psaty Bruce M. , Siscovick David S. , Arking Dan , Sotoodehnia Nona ,   for the SCD working group of the CHARGE Consortium
Published: December 2017

Background

Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. While several risk factors are observationally associated with SCA, the genetic architecture of SCA in the general population remains unknown. Furthermore, understanding which risk factors are causal may help target prevention strategies.

Methods

We carried out a large genome-wide association study (GWAS) for SCA (n=3,939 cases, 25,989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA.

Results

No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (1) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (2) height and BMI, and (3) electrical instability traits (QT and atrial fibrillation), suggesting etiologic roles for these traits in SCA risk.

Conclusions

Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in highrisk populations and the general community.
Ultraconserved elements occupy specific arenas of three-dimensional mammalian genome organization
Authors: McCole Ruth B. , Erceg Jelena , Saylor Wren , Wu Chao-ting
Published: December 2017

This study explores the relationships between three-dimensional genome organization and the ultraconserved elements (UCEs), an enigmatic set of DNA elements that show very high DNA sequence conservation between vertebrate reference genomes. Examining both human and mouse genomes, we interrogate the relationship of UCEs to three features of chromosome organization derived from Hi-C studies. Firstly, we report that UCEs are enriched within contact ‘domains’ and, further, that the UCEs that fall into domains shared across diverse cell types are linked to kidney-related and neuronal processes. In ‘boundaries’, UCEs are generally depleted, with those that do overlap boundaries being overrepresented in exonic UCEs. Regarding loop anchors, UCEs are neither over- nor under-represented, with those present in loop anchors being enriched for splice sites compared to all UCEs. Finally, as all of the relationships we observed between UCEs and genomic features are conserved in the mouse genome, our findings suggest that UCEs contribute to interspecies conservation of genome organization and, thus, genome stability.
Global, multiplexed dendritic computations under in vivo-like conditions
Authors: Ujfalussy Balázs B , Lengyel Máté , Branco Tiago
Published: December 2017

Dendrites integrate inputs in highly non-linear ways, but it is unclear how these non-linearities contribute to the overall input-output transformation of single neurons. Here, we developed statistically principled methods using a hierarchical cascade of linear-nonlinear subunits (hLN) to model the dynamically evolving somatic response of neurons receiving complex spatio-temporal synaptic input patterns. We used the hLN to predict the membrane potential of a detailed biophysical model of a L2/3 pyramidal cell receiving in vivo-like synaptic input and reproducing in vivo dendritic recordings. We found that more than 90% of the somatic response could be captured by linear integration followed a single global non-linearity. Multiplexing inputs into parallel processing channels could improve prediction accuracy by as much as additional layers of local non-linearities. These results provide a data-driven characterisation of a key building block of cortical circuit computations: dendritic integration and the input-output transformation of single neurons during in vivo-like conditions.
Growth and extended survival ofEscherichia coliO157:H7 in soil organic matter
Authors: NandaKafle Gitanjali , Christie Amy A. , Vilain Sébastien , Brözel Volker S.
Published: December 2017

EnterohaemorrhagicEscherichia colisuch as serotype O157:H7 are a leading cause of food-associated outbreaks. While the primary reservoir is associated with cattle, plant foods have been associated as sources of human infection.E. coliis able to grow in the tissue of food plants such as spinach. While fecal contamination is the primary suspect, soil has been underestimated as a potential reservoir. Persistence of bacterial populations in open systems is the product of growth, death, predation, and competition. Here we report thatE. coliO157:H7 can grow using the soluble compounds in soil, and characterize the effect of soil growth in the stationary phase proteome.E. coli933D (stxII-) was cultured in Soil Extracted Soluble Organic Matter (SESOM) and the culturable count determined for 24 d. The proteomes of exponential and stationary phase populations were characterized by 2D gel electrophoresis and protein spots were identified by MALDI-TOF mass spectrometry. While LB controls displayed a death phase, SESOM grown population remained culturable for 24 d, indicating an altered physiological state with superior longevity. This was not due to decreased cell density on entry to stationary phase as 24h SESOM populations concentrated 10-fold retained their longevity. Principal component analysis showed that stationary phase proteomes from SESOM and LB were different. Differences included proteins involved in stress response, motility, membrane and wall composition, nutrient uptake, translation and protein turnover, and anabolic and catabolic pathways, indicating an altered physiological state of soil-grown cells entering stationary phase. The results suggest thatE. colimay be a soil commensal that in absence of predation and competition maintains stable populations in soil.
A cortical pathway modulates sensory input into the olfactory striatum
Authors: White Kate A. , Zhang Yun-Feng , Zhang Zhijian , Bhattarai Janardhan P. , Moberly Andrew H. , in ‘t Zandt Estelle , Mi Huijie , Jia Xianglian , Fuccillo Marc V. , Xu Fuqiang , Ma Minghong , Wesson Daniel W.
Published: December 2017

Sensory cortices process stimuli in manners essential for perception. The piriform ‘primary’ olfactory cortex (PCX) extends dense association fibers into the ventral striatum’s olfactory tubercle (OT), yet the function of this cortico-striatal pathway is unknown. We optically stimulated channelrhodopsin-transduced PCX glutamatergic neurons or their association fibers while recording OT neural activity in mice performing an olfactory task. Activation of PCX neurons or their association fibers within the OT controlled the firing of some OT neurons and bidirectionally modulated odor coding dependent upon the neuron’s intrinsic odor responsivity. Further, patch clamp recordings and retroviral tracing from D1 and D2 dopamine receptor-expressing OT medium spiny neurons revealed this input can be monosynaptic and that both cell types receive most of their input from a specific spatial zone localized within the ventro-caudal PCX. These results demonstrate that the PCX functionally accesses the direct and indirect pathways of the basal ganglia within the OT.
Modulation of formin processivity by profilin and mechanical tension
Authors: Kerleau Mikael , Cao Luyan , Suzuki Emiko , Wioland Hugo , Jouet Sandy , Guichard Bérengère , Lenz Martin , Romet-Lemonne Guillaume , Jégou Antoine
Published: December 2017

Formins are major regulators of actin networks. They enhance actin filament dynamics by remaining processively bound to filament barbed ends. How biochemical and mechanical factors affect formin processivity are open questions. Monitoring individual actin filaments in a microfluidic flow, we report that formin mDia1 dissociates faster under higher ionic strength and when actin concentration is increased. Profilin, known to increase the elongation rate of formin-associated filaments, surprisingly decreases the formin dissociation rate, by bringing formin FH1 domains in transient contact with the barbed end. In contrast, piconewton tensile forces applied to actin filaments accelerate formin dissociation by orders of magnitude, largely overcoming profilin-mediated stabilization. We developed a model of formin conformations and its confrontation to our data indicates the existence of two different dissociation pathways, with force favoring one over the other. How cells limit formin dissociation under tension is now a key question for future studies.
Multiple stable states in microbial communities explained by the stable marriage problem
Authors: Goyal Akshit , Dubinkina Veronika , Maslov Sergei
Published: December 2017

Experimental studies of microbial communities routinely reveal that they have multiple stable states. While each of these states is generally resilient, certain perturbations such as antibiotics, probiotics and diet shifts, result in transitions to other states. Can we reliably both predict such stable states as well as direct and control transitions between them? Here we present a new conceptual model — inspired by the stable marriage problem in game theory and economics — in which microbial communities naturally exhibit multiple stable states, each state with a different species’ abundance profile. Our model’s core ingredient is that microbes utilize nutrients one at a time while competing with each other. Using only two ranked tables, one with microbes’ nutrient preferences and one with their competitive abilities, we can determine all possible stable states as well as predict inter-state transitions, triggered by the removal or addition of a specific nutrient or microbe. Further, using an example of 7 Bacteroides species common to the human gut utilizing 9 polysaccharides, we predict that mutual complementarity in nutrient preferences enables these species to coexist at high abundances.
Performance Assessment and Selection of Normalization Procedures for Single-Cell RNA-seq
Authors: Cole Michael B. , Risso Davide , Wagner Allon , DeTomaso David , Ngai John , Purdom Elizabeth , Dudoit Sandrine , Yosef Nir
Published: December 2017

Systematic measurement biases make data normalization an essential preprocessing step in single-cell RNA sequencing (scRNA-seq) analysis. There may be multiple, competing considerations behind the assessment of normalization performance, some of them study-specific. Because normalization can have a large impact on downstream results (e.g., clustering and differential expression), it is critically important that practitioners assess the performance of competing methods.

We have developedscone— a flexible framework for assessing normalization performance based on a comprehensive panel of data-driven metrics. Through graphical summaries and quantitative reports,sconesummarizes performance trade-offs and ranks large numbers of normalization methods by aggregate panel performance. The method is implemented in the open-source Bioconductor R software package scone. We demonstrate the effectiveness ofsconeon a collection of scRNA-seq datasets, generated with different protocols, including Fluidigm C1 and 10x platforms. We show that top-performing normalization methods lead to better agreement with independent validation data.
Does 10-Hz cathodal oscillating current of the parieto-occipital lobe modulate target detection?
Authors: Sheldon Sarah S. , Mathewson Kyle E.
Published: December 2017

The phase of alpha (8-12 Hz) brain oscillations have been associated with moment to moment changes in visual attention and awareness. Previous work has demonstrated that endogenous oscillations and subsequent behavior can be modulated by oscillating transcranial current stimulation (otCS). The purpose of the current study is to establish the efficacy of cathodal otCS for modulation of the ongoing alpha brain oscillations, allowing for modulation of individual’s visual perception. Thirty-six participants performed a target detection with sham and 10-Hz cathodal otCS. Each participant had two practice and two experimental sets composed of three blocks of 128 trials per block. Stimulating electrodes were small square sponges (20 cm2) placed on the participant’s head with the anode electrode at Cz and the cathode electrode at Oz. A 0.5 mA current was applied at the cathode electrode every 100 ms (10 Hz frequency) during the otCS condition. The same current and frequency was applied for the first 10-20 s of the sham condition, after which the current was turned off. Target detection rates were separated into ten 10-ms bins based on the latency between the stimulation/sham pulse and target onset. Target detection rates were then compared between the sham and otCS experimental conditions across the ten bins in order to test for effects of otCS phase on target detection. We found no significant difference in target detection rates between the sham and otCS conditions, and discuss potential reasons for the apparent inability of cathodal otCS to effectively modulate visual perception.
Comparison of video-based and sensor-based head impact exposure
Authors: Kuo Calvin , Wu Lyndia , Loza Jesus , Senif Daniel , Anderson Scott C. , Camarillo David B.
Published: December 2017

Previous research has sought to quantify head impact exposure using wearable kinematic sensors. However, many sensors suffer from poor accuracy in estimating impact kinematics and count, motivating the need for additional independent impact exposure quantification for comparison. Here, we equipped seven collegiate American football players with instrumented mouthguards, and video recorded practices and games to compare video-based and sensor-based exposure rates and impact location distributions. Over 50 player-hours, we identified 271 helmet contact periods in video, while the instrumented mouthguard sensor recorded 2,032 discrete head impacts. Matching video and mouthguard real-time stamps yielded 193 video-identified helmet contact periods and 217 sensor-recorded impacts. To compare impact locations, we binned matched impacts into frontal, rear, side, oblique, and top locations based on video observations and sensor kinematics. While both video-based and sensor-based methods found similar location distributions, our best method utilizing integrated linear and angular position only correctly predicted 81 of 217 impacts. Finally, based on the activity timeline from video assessment, we also developed a new exposure metric unique to American football quantifying number of cross-verified sensor impacts per player-play. We found significantly higher exposure during games (0.35, 95% CI: 0.29-0.42) than practices (0.20, 95% CI: 0.17-0.23) (p<0.05). In the traditional impacts per player-hour metric, we observed higher exposure during practices (4.7) than games (3.7) due to increased player activity in practices. Thus, our exposure metric accounts for variability in on-field participation. While both video-based and sensor-based exposure datasets have limitations, they can complement one another to provide more confidence in exposure statistics.
High throughput single cell RNA-seq of developing mouse kidney and human kidney organoids reveals a roadmap for recreating the kidney
Authors: Combes Alexander N. , Phipson Belinda , Zappia Luke , Lawlor Kynan T. , Er Pei Xuan , Oshlack Alicia , Little Melissa H.
Published: December 2017

Recent advances in our capacity to differentiate human pluripotent stem cells to human kidney tissue are moving the field closer to novel approaches for renal replacement. Such protocols have relied upon our current understanding of the molecular basis of mammalian kidney morphogenesis. To date this has depended upon population based-profiling of non-homogenous cellular compartments. In order to improve our resolution of individual cell transcriptional profiles during kidney morphogenesis, we have performed 10x Chromium single cell RNA-seq on over 6000 cells from the E18.5 developing mouse kidney, as well as more than 7000 cells from human iPSC-derived kidney organoids. We identified 16 clusters of cells representing all major cell lineages in the E18.5 mouse kidney. The differentially expressed genes from individual murine clusters were then used to guide the classification of 16 cell clusters within human kidney organoids, revealing the presence of distinguishable stromal, endothelial, nephron, podocyte and nephron progenitor populations. Despite the congruence between developing mouse and human organoid, our analysis suggested limited nephron maturation and the presence of ‘off target’ populations in human kidney organoids, including unidentified stromal populations and evidence of neural clusters. This may reflect unique human kidney populations, mixed cultures or aberrant differentiation in vitro. Analysis of clusters within the mouse data revealed novel insights into progenitor maintenance and cellular maturation in the major renal lineages and will serve as a roadmap to refine directed differentiation approaches in human iPSC-derived kidney organoids.
Metals enable a non-enzymatic acetyl CoA pathway
Authors: Varma Sreejith J. , Muchowska Kamila B. , Chatelain Paul , Moran Joseph
Published: December 2017

The evolutionary origins of carbon fixation, the biological conversion of CO2to metabolites, remain unclear. Phylogenetics indicates that the AcCoA pathway, the reductive fixation of CO2to acetyl and pyruvate, was a key biosynthetic route used by the Last Universal Common Ancestor (LUCA) to build its biochemistry. However, debate exists over whether CO2fixation is a relatively late invention of pre-LUCA evolution or whether it dates back to prebiotic chemistry. Here we show that zero-valent forms of the transition metals known to act as co-factors in the AcCoA pathway (Fe0, Ni0, Co0) fix CO2on their surface in a manner closely resembling the biological pathway, producing acetate and pyruvate in near mM concentrations following cleavage from the surface. The reaction is robust over a wide range of temperatures and pressures with acetate and pyruvate constituting the major products in solution at 1 bar of CO2and 30 °g;C. The discovered conditions also promote 7 of the 11 steps of the rTCA cycle and amino acid synthesis, providing a stunning direct connection between simple inorganic chemistry and ancient CO2-fixation pathways. The results strongly sup-port the notion that CO2-fixation pathways are an outgrowth of spontaneous geochemistry.
Complementary studies of lipid membrane dynamics using iSCAT and super-resolved Fluorescence Correlation Spectroscopy
Authors: Reina Francesco , Galiani Silvia , Shrestha Dilip , Sezgin Erdinc , de Wit Gabrielle , Cole Daniel , Lagerholm B. Christoffer , Kukura Philip , Eggeling Christian
Published: December 2017

Observation techniques with high spatial and temporal resolution, such as single-particle tracking (SPT) based on interferometric Scattering (iSCAT) microscopy, and fluorescence correlation spectroscopy applied on a super-resolution STED microscope (STED-FCS), have revealed new insights of the molecular organization of membranes. While delivering complementary information, there are still distinct differences between these techniques, most prominently the use of fluorescent dye-tagged probes for STED-FCS and a need for larger scattering gold nanoparticle tags for iSCAT. In this work we have used lipid analogues tagged with a hybrid fluorescent tag – gold nanoparticle construct, to directly compare the results from STED-FCS and iSCAT measurements of phospholipid diffusion on a homogeneous Supported Lipid Bilayer (SLB). These comparative measurements showed that while the mode of diffusion remained free, at least at the spatial (>40 nm) and temporal (50 ≤ t ≤ 100 ms) scales probed, the diffussion coefficient was reduced by 20- to 60-fold when tagging with 20 and 40 nm large gold particles as compared to when using dye-tagged lipid analogues. These FCS measurements of hybrid fluorescent tag – gold nanoparticle labeled lipids also revealed that commercially supplied streptavidin-coated gold nanoparticles contain large quantities of free streptavidin. Finally, the values of apparent diffusion coefficients obtained by STED-FCS and iSCAT differed by a factor of 2-3 across the techniques, while relative differences in mobility between different species of lipid analogues considered were identical in both approaches. In conclusion, our experiments reveal that large and potentially crosslinking scattering tags introduce a significant slow-down in diffusion on SLBs but no additional bias, and our labeling approach creates a new way of exploiting complementary information from STED-FCS and iSCAT measurements.
Sleep spindle refractoriness segregates periods of memory reactivation
Authors: Antony James W. , Piloto Luis , Wang Margaret , Pacheco Paula , Norman Kenneth A. , Paller Ken A.
Published: December 2017

The stability of long-term memories is enhanced by reactivation during sleep. Correlative evidence has linked memory reactivation with thalamocortical sleep spindles, although their functional role is poorly understood. Our initial study replicated this correlation but also demonstrated a novel rhythmicity to spindles, such that spindles are less likely to occur immediately following other spindles. We leveraged this rhythmicity to test the role of spindles in memory by using real-time spindle tracking to present cues inside versus outside the presumptive refractory period; as predicted, cues presented outside the refractory period led to better memory. Our findings reveal a previously undescribed neural mechanism whereby spindles segment sleep into two distinct substates: prime opportunities for reactivation and gaps that segregate reactivation events.

One Sentence Summary

The characteristic timing of sleep spindles regulates when memories can be reactivated during sleep.
S1PR3 mediates itch and pain via distinct TRP channel-dependent pathways
Authors: Hill Rose Z. , Morita Takeshi , Brem Rachel B. , Bautista Diana M.
Published: December 2017

Sphingosine 1-phosphate (S1P) is a bioactive signaling lipid associated with a variety of chronic pain and itch disorders. S1P signaling has been linked to cutaneous pain, but its role in itch has not yet been studied. Here we find that S1P triggers itch and pain in mice in a concentration-dependent manner, with low levels triggering acute itch alone, and high levels triggering both pain and itch. Calcium imaging and electrophysiological experiments revealed that S1P signals via S1PR3 and TRPA1 in a subset of pruriceptors, and via S1PR3 and TRPV1 in a subset of heat nociceptors. And in behavioral assays, S1P-evoked itch was selectively lost in mice lacking TRPA1, whereas S1P-evoked acute pain and heat hypersensitivity were selectively lost in mice lacking TRPV1. We conclude that S1P acts via different cellular and molecular mechanisms to trigger itch and pain. Our discovery elucidates the diverse roles that S1P signaling plays in somatosensation and provides insight into how itch and pain are discriminated in the periphery.

Significance Statement

Itch and pain are major health problems with few effective treatments. Here, we show that the pro-inflammatory lipid S1P and its receptor S1PR3 trigger itch and pain behaviors via distinct molecular and cellular mechanisms. Our results provide a detailed understanding of the roles that S1P and S1PR3 play in somatosensation, highlighting their potential as targets for analgesics and antipruritics, and provide new insight into the mechanistic underpinnings of itch versus pain discrimination in the periphery.
Mapping mutational effects along the evolutionary landscape of HIV envelope
Authors: Haddox Hugh K. , Dingens Adam S. , Hilton Sarah K. , Overbaugh Julie , Bloom Jesse D.
Published: December 2017

The immediate evolutionary space accessible to HIV is largely determined by how single amino-acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here we quantify the effects on viral growth of all amino-acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino-acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs -- and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env's mutational tolerance during HIV evolution, although the amino-acid preferences of most sites are conserved between moderately diverged viral strains.
Experimental study of EUV mirror radiation damage resistance under long-term free-electron laser exposures below the single-shot damage threshold
Authors: Makhotkin Igor A. , Sobierajski Ryszard , Chalupský Jaromir , Tiedtke Kai , de Vries Gosse , Störmer Michael , Scholze Frank , Siewert Frank , van de Kruijs Robbert W. E. , Milov Igor , Louis Eric , Jacyna Iwanna , Jurek Marek , Klinger Dorota , Nittler Laurent , Syryanyy Yevgen , Juha Libor , Hájková Věra , Vozda Vojtěch , Burian Tomáš , Saksl Karel , Faatz Bart , Keitel Barbara , Plönjes Elke , Schreiber Siegfried , Toleikis Sven , Loch Rolf , Hermann Martin , Strobel Sebastian , Nienhuys Han-Kwang , Gwalt Grzegorz , Mey Tobias , Enkisch Hartmut
Published: December 2017

The durability of grazing- and normal-incidence optical coatings has been experimentally assessed under free-electron laser irradiation at various numbers of pulses up to 16 million shots and various fluence levels below 10% of the single-shot damage threshold. The experiment was performed at FLASH, the Free-electron LASer in Hamburg, using 13.5 nm extreme UV (EUV) radiation with 100 fs pulse duration. Polycrystalline ruthenium and amorphous carbon 50 nm thin films on silicon substrates were tested at total external reflection angles of 20° and 10° grazing incidence, respectively. Mo/Si periodical multilayer structures were tested in the Bragg reflection condition at 16° off-normal angle of incidence. The exposed areas were analysed post-mortem using differential contrast visible light microscopy, EUV reflectivity mapping and scanning X-ray photoelectron spectroscopy. The analysis revealed that Ru and Mo/Si coatings exposed to the highest dose and fluence level show a few per cent drop in their EUV reflectivity, which is explained by EUV-induced oxidation of the surface.
Caesarean section wound infection surveillance: Information for action
Authors: Scheck Simon M. , Blackmore Timothy , Maharaj Dushyant , Langdana Fali , Elder Rosalie E.
Published: December 2017

Surgical site infection (SSI) following caesarean section is common, resulting in significant morbidity. Several factors are known to contribute to wound infection, including maternal, procedural and antibiotic factors. We sought to clarify these issues and sought opportunities to make improvements. A retrospective cohort study was performed assessing all women who underwent caesarean section in 2014 and 2015 at Wellington Hospital. Any women with culture‐positive wound samples within 30 days of surgery were identified, and clinical notes reviewed. Odds ratios (OR) were calculated for available maternal, procedural and antibiotic risk factors. Two simplified surveillance techniques were also tested for their abilities to identify significant trends. The study included 2231 women, of whom 116 (5.2%) were identified as having SSI. Maternal obesity (body mass index (BMI) ≥ 30) was associated with significant SSI risk (OR 4.1, P < 0.001). The pathogen distribution was significantly different between women with BMI < 30 and BMI ≥ 30 (P < 0.001). Increased cefazolin dose based on BMI (3 g dose for BMI ≥ 30) was associated with a significant reduction in SSI (OR 0.309, P < 0.001) and was administered in 74.1% of obese women receiving cefazolin. Māori women had an increased SSI risk (OR 2.1, P = 0.019), as did Samoan women (OR 3.0, P = 0.002). The study reinforces other studies showing that raised BMI is the single biggest risk factor for surgical site infection post‐caesarean section. Surveillance using simplified techniques appears to be adequate to identify trends. We believe that concentrating on appropriate antibiotic dosing and targeting special wound care measures will be pivotal interventions in improving outcomes in high‐risk groups.
Heightened parental stress in mothers of children with visual impairment
Authors: Huurneman Bianca
Published: December 2017

This commentary is on the original article by Sakkalou et al. on pages 290–298 of this issue.
A complex ventricular septal defect following transcatheter aortic valve implantation evaluated by 3D transthoracic echocardiography
Authors: Barbati Giovanni , Zeppellini Roberto , Erente Giovanna , Ramondo Angelo B.
Published: December 2017

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of elderly patients with symptomatic severe aortic valve stenosis. Among the possible TAVI complications, a rare one is the annular/left ventricular outflow tract rupture. We report a rare case of a late complex ventricular septal defect (VSD) following TAVI with a balloon‐expandable prosthesis, conservatively managed. Our case demonstrates the role of 3D transthoracic echocardiography (3DTTE) in the accurate diagnosis of this TAVI complication and suggests that, in some cases, it can be used as an alternative to other diagnostic tools, such as transesophageal echocardiography, cardiac catheterization, and computed tomography.
Perspectives of patients with non‐insulin‐treated type 2 diabetes on self‐monitoring of blood glucose: A qualitative study
Authors: Chen Chen‐Mei , Hung Li‐Chen , Chen Yang‐Lin , Yeh Mei Chang
Published: December 2017

Aims and objectives

To explore experiences of self‐monitoring of blood glucose among patients with non‐insulin‐treated type 2 diabetes.

Background

Self‐monitoring of blood glucose is essential to diabetes care and facilitates glycaemic control. Patients’ perspectives of self‐monitoring of blood glucose have seldom been discussed in the literature, and engagement in self‐monitoring of blood glucose is consistently low.

Design

The descriptive phenomenological method was used.

Methods

Purposive sampling was conducted to recruit participants from the endocrinology departments of medical institutions in Taiwan based on the following criteria: (i) having a medical diagnosis of type 2 diabetes, (ii) not being treated with insulin, (iii) having engaged in self‐monitoring of blood glucose at least once within the preceding 6 months, (iv) being at least 20 years old and (v) not having any major mental or cognitive disorders. Data were collected in outpatient consultation rooms, the participants’ homes and other settings where the participants felt secure and comfortable. In‐depth interviews were conducted to collect data from 16 patients with diabetes.

Results

The participants perceived that lifestyle affected blood glucose levels and did not know how to handle high or low blood glucose levels. Their willingness to continue self‐monitoring of blood glucose depended on whether healthcare professionals checked or discussed their blood glucose levels with them.

Conclusions

The patients’ knowledge regarding blood glucose variation and healthcare professionals’ attitudes affected the patients’ self‐monitoring of blood glucose behaviours. The empirical findings illustrated self‐monitoring of blood glucose experiences and recommended that healthcare professionals’ closely attend to patients’ requirements and responses to diabetes and incorporate the self‐monitoring of blood glucose into therapy plans.

Relevance to clinical practice

Healthcare professionals should reinforce patients’ knowledge on appropriate responses to high and low blood glucose levels, intervene appropriately, discuss self‐monitoring of blood glucose results with patients and track these results.
Maxima in the thermodynamic response and correlation functions of deeply supercooled water
Authors: Kim Kyung Hwan , Späh Alexander , Pathak Harshad , Perakis Fivos , Mariedahl Daniel , Amann-Winkel Katrin , Sellberg Jonas A. , Lee Jae Hyuk , Kim Sangsoo , Park Jaehyun , Nam Ki Hyun , Katayama Tetsuo , Nilsson Anders
Published: December 2017

Pointing to a second critical point

One explanation for the divergence of many of the thermodynamic properties of water is that there is a critical point in deeply supercooled water at some positive pressure. For bulk water samples, these conditions are described as “no man's land,” because ice nucleates before such temperatures can be reached. Kim
et al.
used femtosecond x-ray laser pulses to probe micrometer-sized water droplets cooled to 227 K (see the Perspective by Gallo and Stanley). The temperature dependence of the isothermal compressibility and correlation length extracted from x-ray scattering functions showed maxima at 229 K for H
2
O and 233 K for D
2
O, rather than diverging to infinity. These results point to the existence of the Widom line, a locus of maximum correlation lengths emanating from a critical point in the supercooled regime.

Science
, this issue p.
1589
; see also p.
1543
Aminoarabinosylation of Lipid A Is Critical for the Development of Colistin Resistance in Pseudomonas aeruginosa
Authors: Lo Sciuto Alessandra , Imperi Francesco
Published: December 2017

Lipid A aminoarabinosylation is invariably associated with colistin resistance in
Pseudomonas aeruginosa
; however, the existence of alternative aminoarabinosylation-independent colistin resistance mechanisms in this bacterium has remained elusive. By combining reverse genetics with experimental evolution assays, we demonstrate that a functional lipid A aminoarabinosylation pathway is critical for the acquisition of colistin resistance in reference and clinical
P. aeruginosa
isolates. This highlights lipid A aminoarabinosylation as a promising target for the design of colistin adjuvants against
P. aeruginosa
.
All-cause mortality in adults with and without type 2 diabetes: findings from the national health monitoring in Germany
Authors: Röckl Susanne , Brinks Ralph , Baumert Jens , Paprott Rebecca , Du Yong , Heidemann Christin , Scheidt-Nave Christa
Published: December 2017

Objective

To estimate age-specific and sex-specific all-cause mortality among adults with and without type 2 diabetes (T2D) in Germany.

Research design and methods

The German National Health Interview and Examination Survey 1998 (GNHIES98) included a mortality follow-up (median follow-up time 12.0 years) of its nationwide sample representative of the population aged 18–79 years. After exclusion of participants with type 1 diabetes, age- and sex-stratified mortality rates (MR) were calculated for 330 GNHIES98 participants with diagnosed T2D (self-reported diagnosis or antidiabetic medication), 245 with undiagnosed T2D (no diagnosed T2D, glycated hemoglobin A1c ≥6.5% (≥48 mmol/mol)), and 5975 without T2D. Mortality rate ratios (MRR) comparing MR of persons with and without T2D were estimated. Age-/sex-standardized MR and MRR were calculated including persons aged 45 years or older. MRR were used to estimate the number of years of life lost (YLL) due to diagnosed diabetes in 2010.

Results

Over 75 994 person-years, 73 persons with undiagnosed T2D, 103 with diagnosed T2D, and 425 persons without T2D died. MRR were significantly higher in younger age groups, except for analyses limited to women or diagnosed T2D. Age- and sex-standardized MRR (95% CI) among persons aged 45 years or older were 1.96 (1.41 to 2.71) for undiagnosed, 1.68 (1.26 to 2.23) for diagnosed, and 1.82 (1.45 to 2.28) for total (undiagnosed or diagnosed) T2D. Sex-stratified analysis revealed similar age-standardized MRR for undiagnosed (1.56 (0.79 to 3.06)) and diagnosed T2D (1.56 (1.03 to 2.37)) among women, and a higher age-standardized MRR for undiagnosed (2.06 (1.43 to 2.97)) than diagnosed T2D (1.70 (1.10 to 2.63)) among men. YLL due to diagnosed diabetes in Germany in 2010 were 164 600 (35 000 to 279 300) among women and 169 900 (28 300 to 328 300) among men.

Conclusions

In Germany, age- and sex-standardized all-cause mortality is almost twice as high for adults with T2D as for adults without T2D. The T2D-associated excess risk of mortality appears to be most pronounced in younger adults and among men unaware of their T2D.
Confidence in palliative care issues by medical students and internal medicine residents
Authors: Storarri Ana Carolina Montouro , de Castro Giovana Dalmedico , Castiglioni Lilian , Cury Patricia Maluf
Published: December 2017

Background

Palliative care (PC) is a relatively new field in Brazil, but this knowledge is of great importance in medical practice.

Objective

To evaluate the degree of confidence among medical students and first-year and second-year internal medicine residents in addressing issues of death and terminal illness with patients and their families.

Method

A modified version of the Self-Efficacy in Palliative Care Scale was applied to 293 students in their first year to sixth year at the School of Medicine of São José do Rio Preto and to 43 residents in their first year or second year of medical practice at the same institution in Brazil, in 2015. The questionnaire evaluated students' opinions on the need to include theoretical and practical classes on PC in the medical school.

Results

Students in their fifth year of medical school were more confident than the students in their first, second, third and fourth years; there were no statistically significant differences between fifth-year students, sixth-year students and the internal medicine residents.

Conclusion

Residents were more confident than all of the medical school students except those in their fifth year (P<0.05) because they have more contact with terminally ill patients than other students do; fifth-year medical students are likely overestimating their abilities.
Factors associated with condom use among men and women living with HIV in Lilongwe, Malawi: a cross-sectional study
Authors: Haddad Lisa B , Tang Jennifer H , Krashin Jamie , Ng’ambi Wingston , Tweya Hannock , Samala Bernadette , Chiwoko Jane , Chaweza Thomas , Hosseinipour Mina C , Lathrop Eva , Jamieson Denise J , Phiri Sam
Published: December 2017

Background

Understanding the influences on condom use among men and women living with HIV is critical to tailoring sexually transmitted infection/HIV prevention efforts.

Methods

This is a sub-analysis of a cross-sectional survey including 255 women and 220 men who were sexually active, HIV-positive, and attending HIV care visits in Lilongwe, Malawi. We estimated adjusted prevalence ratios (aPRs) to evaluate for factors associated with consistent condom use (always using condoms in the past month) and use at last coitus for men and women in separate models.

Results

Among women: 38% and 55% reported consistent condom use and condom use at last coitus, respectively. For women, consistent use and use at last coitus were positively associated with the ability to refuse sex without condoms and shared decision-making compared with making the decision alone regarding condom use, and negatively associated with desire for children in the future. Consistent use also increased with longer antiretroviral therapy (ART) use (≥1 year compared with no ART use). Among men: 51% and 69% reported consistent condom use and condom use at last coitus, respectively. For men, the ability to refuse sex without condoms was associated with consistent use and use at last coitus, and believing that condoms should be used with other contraception was associated with consistent use.

Conclusions

Our findings demonstrate ongoing low condom utilisation among HIV-positive individuals, and highlight that ART and contraceptive use do not deter condom use. Efforts to increase condom utilisation must recognise individual-level factors that influence use and should focus on relationship dynamics and promotion of empowerment and self-efficacy.
The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure
Authors: Marinaccio Alessandro , Corfiati Marisa , Binazzi Alessandra , Di Marzio Davide , Scarselli Alberto , Ferrante Pierpaolo , Bonafede Michela , Verardo Marina , Mirabelli Dario , Gennaro Valerio , Mensi Carolina , Schallemberg Gert , Mazzoleni Guido , Merler Enzo , Girardi Paolo , Negro Corrado , D’Agostin Flavia , Romanelli Antonio , Chellini Elisabetta , Silvestri Stefano , Pascucci Cristiana , Calisti Roberto , Stracci Fabrizio , Romeo Elisa , Ascoli Valeria , Trafficante Luana , Carrozza Francesco , Angelillo Italo Francesco , Cavone Domenica , Cauzillo Gabriella , Tallarigo Federico , Tumino Rosario , Melis Massimo , Iavicoli Sergio
Published: December 2017

Introduction

The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register.

Methods

Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated.

Results

In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries.

Conclusions

The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.
Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study
Authors: Wang Zhang , Singh Richa , Miller Bruce E , Tal-Singer Ruth , Van Horn Stephanie , Tomsho Lynn , Mackay Alexander , Allinson James P , Webb Adam J , Brookes Anthony J , George Leena M , Barker Bethan , Kolsum Umme , Donnelly Louise E , Belchamber Kylie , Barnes Peter J , Singh Dave , Brightling Christopher E , Donaldson Gavin C , Wedzicha Jadwiga A , Brown James R
Published: December 2017

Background

Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon.

Methods

We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium.

Results

The microbiome composition was similar among centres and between stable and exacerbations except for a small significant decrease ofVeillonellaat exacerbations. The abundance ofMoraxellawas negatively associated with bacterial alpha diversity. Microbiomes were distinct between exacerbations associated with bacteria versus eosinophilic airway inflammation. Dysbiosis at exacerbations, measured as significant within subject deviation of microbial composition relative to baseline, was present in 41% of exacerbations. Dysbiosis was associated with increased exacerbation severity indicated by a greater fall in forced expiratory volume in one second, forced vital capacity and a greater increase in CAT score, particularly in exacerbations with concurrent eosinophilic inflammation. There was a significant difference of temporal variability of microbial alpha and beta diversity among centres. The variation of beta diversity significantly decreased in those subjects with frequent historical exacerbations.

Conclusions

Microbial dysbiosis is a feature of some exacerbations and its presence, especially in concert with eosinophilic inflammation, is associated with more severe exacerbations indicated by a greater fall in lung function.

Trial registration number

Results,NCT01620645.
Canine pododermatitis caused by Pichia jadinii
Authors: Pieper Jason , Piccione Michelle
Published: December 2017

A five‐year‐old male neutered mixed breed dog was presented with asymmetric pododermatitis. The left front paw was characterised by interdigital hyperplasia and erythema, particularly between the third and fourth digits on the palmar aspect. The area was sampled with a 6‐mm punch biopsy for histopathological evaluation, aerobic culture and anaerobic culture. Histopathology from the footpad lesion revealed pyogranulomatous dermatitis and panniculitis. Periodic acid‐Schiff (PAS) stain of the tissues revealed several hair shafts containing PAS‐positive hyphae. Fungal PCR was positive and the fungal organism was identified as Pichia jadinii by DNA sequencing. The dog was treated systemically with the antifungal ketoconazole. After initiation of therapy the lesion resolved within eight weeks; the ketoconazole was discontinued after three months and no relapse was seen over the following year. P jadinii should be considered as a differential diagnosis for pododermatitis in dogs. Identification via PCR and DNA sequencing may be needed to identify this organism.