bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale interaction effects reveal missing heritability in schizophrenia, bipolar disorder and posttraumatic stress disorder
Authors: Woo H J , Yu C , Kumar K , Reifman J
Published: April 2017

Genetic susceptibility factors behind psychiatric disorders typically contribute small effects individually. A possible explanation for the missing heritability is that the effects of common variants are not only polygenic but also non-additive, appearing only when interactions within large groups are taken into account. Here, we tested this hypothesis for schizophrenia (SZ) and bipolar disorder (BP) disease risks, and identified genetic factors shared with posttraumatic stress disorder (PTSD). When considered independently, few single-nucleotide polymorphisms (SNPs) reached genome-wide significance. In contrast, when SNPs were selected in groups (containing up to thousands each) and the collective effects of all interactions were estimated, the association strength for SZ/BP rose dramatically with a combined sample size of 7187 cases and 8309 controls. We identified a large number of genes and pathways whose association was significant only when interaction effects were included. The gene with highest association wasCSMD1, which encodes a negative regulator of complement activation. Pathways for glycosaminoglycan (GAG) synthesis exhibited strong association in multiple contexts. Taken together, highly associated pathways suggested a pathogenesis mechanism where maternal immune activation causes disruption of neurogenesis (compounded by impaired cell cycle, DNA repair and neuronal migration) and deficits in cortical interneurons, leading to symptoms triggered by synaptic pruning. Increased risks arise from GAG deficiencies causing complement activation and excessive microglial action. Analysis of PTSD data sets suggested an etiology common to SZ/BP: interneuron deficiency can also lead to impaired control of fear responses triggered by trauma. We additionally found PTSD risk factors affecting synaptic plasticity and fatty acid signaling, consistent with the fear extinction model. Our results suggest that much of the missing heritability of psychiatric disorders resides in non-additive interaction effects.
Dual antioxidant/pro-oxidant behavior of the tryptophan metabolite 3-hydroxyanthranilic acid: a theoretical investigation of reaction mechanisms and kinetics
Authors: Pérez-González Adriana , Alvarez-Idaboy Juan Raúl , Galano Annia
Published: April 2017

Potent antioxidant in the absence of metal ions, responsible for the activity usually attributed to tryptophan. Pro-oxidant in the presence of metal ions; this effect increases with the pH.
Thermodynamic and morphological characterization of Turing patterns in non-isothermal reaction–diffusion systems
Authors: Serna Horacio , Muñuzuri Alberto P. , Barragán Daniel
Published: April 2017

The morphology and entropy production of Turing patterns are studied under real non-isothermal conditions in order to gain insights into their energy economy.
An approximate full-dimensional quantum dynamics study of the mode specificity in the dissociative chemisorption of D2O on rigid Cu(111)
Authors: Liu Tianhui , Fu Bina , Zhang Dong H.
Published: April 2017

The approximate 9D dissociation probabilities for D2O/Cu(111) are obtained to investigate the influence of mode specificity on reaction dynamics.
Ab initio study of the role of oxygen and excess electrons in the degradation of CH3NH3PbI3
Authors: Zhang Linghai , Sit Patrick H.-L.
Published: April 2017

Excess electrons from photo-excitation, impurities and defects play a significant role in the degradation of CH3NH3PbI3 (MAPbI3) perovskite in air.
Crystallographic orientation propagation in metal halide perovskite thin films
Authors: Chen Alexander Z. , Foley Benjamin J. , Ma Jennifer H. , Alpert Matthew R. , Niezgoda J. Scott , Choi Joshua J.
Published: April 2017

Preferential crystallographic orientation can propagate through metal halide perovskite thin films.
Pro-inflammatory cytokine-driven PI3K/Akt/Sp1 signalling and H2S production facilitates the pathogenesis of severe acute pancreatitis
Authors: Liu Ying , Liao Ribin , Qiang Zhanrong , Zhang Cheng
Published: April 2017

Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulphide (H2S) that impairs the gastrointestinal (GI) system. However, the exact mechanism of H2S in the regulation of SAP is yet to be elucidated. In the present paper, we used a rat model of SAP to evaluate the role of H2S on intestinal motility by counting the number of bowel movements and investigating the effect of H2S on inflammation. We treated colonic muscle cells (CMCs) with SAP plasma, tumour necrosis factor-α (TNF-α) or interleukin-6 (IL-6) and measured the expressions of H2S-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and Sp1 and PI3K/Akt by using quantitative PCR, Western blotting and immunohistochemical detection. We used the PI3K inhibitor LY294002 and the siRNA si-Sp1 to suppress the activity of the PI3K/Akt/Sp1 signalling pathway. We found that, in the SAP rat model, H2S facilitated an inhibitory effect on intestinal motility and enhanced the inflammatory response caused by SAP (P<0.05). The expressions of CSE and CBS in CMCs were significantly increased after treatment with TNF-α or IL-6 (P<0.05). Blocking the PI3K/Akt/Sp1 pathway remarkably inhibited the synthesis of CSE and CBS. Our data demonstrated that H2S plays a vital role in the pathogenesis of SAP and that SAP is modulated by inflammation driven by the PI3K/Akt/Sp1 signalling pathway.
Finite element modeling of melting and fluid flow in the laser-heated diamond-anvil cell
Authors: Gomez-Perez N. , Rodriguez J. F. , McWilliams R. S.
Published: April 2017

The laser-heated diamond anvil cell is widely used in the laboratory study of materials behavior at high-pressure and high-temperature, including melting curves and liquid properties at extreme conditions. Laser heating in the diamond cell has long been associated with fluid-like motion in samples, which is routinely used to determine melting points and is often described as convective in appearance. However, the flow behavior of this system is poorly understood. A quantitative treatment of melting and flow in the laser-heated diamond anvil cell is developed here to physically relate experimental motion to properties of interest, including melting points and viscosity. Numerical finite-element models are used to characterize the temperature distribution, melting, buoyancy, and resulting natural convection in samples. We find that continuous fluid motion in experiments can be explained most readily by natural convection. Fluid velocities, peaking near values of microns per second for plausible viscosities, are sufficiently fast to be detected experimentally, lending support to the use of convective motion as a criterion for melting. Convection depends on the physical properties of the melt and the sample geometry and is too sluggish to detect for viscosities significantly above that of water at ambient conditions, implying an upper bound on the melt viscosity of about 1 mPa s when convective motion is detected. A simple analytical relationship between melt viscosity and velocity suggests that direct viscosity measurements can be made from flow speeds, given the basic thermodynamic and geometric parameters of samples are known.
Note: Experimental setup for measuring the barocaloric effect in polymers: Application to natural rubber
Authors: Bom N. M. , Usuda E. O. , Guimarães G. M. , Coelho A. A. , Carvalho A. M. G.
Published: April 2017

Barocaloric materials have shown to be promising alternatives to the conventional vapor-compression refrigeration technologies. Nevertheless, barocaloric effect (σb-CE) has not been extensively examined for many classes of materials up to now. Aiming at fulfilling this gap, the present paper describes the development of a high-pressure experimental setup for measuring the σb-CE in polymers. The design allows simultaneous measurements of temperature, pressure, and strain during the barocaloric cycle. The system proved to be fully functional through basic experiments using natural rubber. Samples exhibited large temperature variations associated with the σb-CE. Strain-temperature curves were also obtained, which could allow indirect measurements of the isothermal entropy change.
Anomalous sound attenuation in Voronoi liquid
Authors: Ruscher C. , Semenov A. N. , Baschnagel J. , Farago J.
Published: April 2017

The physics of simple fluids in the hydrodynamic limit and notably the connection between the proper microscopic scales and the macroscopic hydrodynamical description are nowadays well understood. In particular, the three peak shape of the dynamical structure factor S(k,ω) is a universal feature, as well as the k-dependence of the peak position (∝k) and width ∝k2, the latter accounting for the sound attenuation rate. In this paper, we present a theoretical model of monodisperse fluid, whose interactions are defined via the Voronoi tessellations of the configurations [called the Voronoi liquid and first studied in Ruscher et al., Europhys. Lett. 112, 66003 (2015)], which displays at low temperatures a marked violation of the universal features of S(k,ω) with a sound attenuation rate only ∝k. This anomalous behaviour, which apparently violates the basic symmetries of the liquid state, is traced back to the existence of a time scale which is both short enough for the viscoelastic features of the liquid to impact the relaxational dynamics and however long enough for the momentum diffusion to be substantially slower than the sound propagation on that characteristic time.
Observation of oxygen vacancy migration in memory devices based on ZnO nanoparticles
Authors: Li Cheng , Vaynzof Yana , Lakhwani Girish , Beirne Gareth J. , Wang Jianpu , Greenham Neil C.
Published: April 2017

We investigate the mechanism of resistive switching in non-volatile memory devices based on an ITO/ZnO nanoparticles/Al structure using electroabsorption (EA) spectroscopy and X-ray photoelectron spectroscopy (XPS). By incorporating a small amount of low-bandgap organic semiconductor, poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT), as a probe molecule for EA characterization, we study the change in the built-in potential during the switching process under different ambient conditions. We compare the concentrations of oxygen vacancies between the Al/ZnO interface and the bulk of the ZnO nanoparticle film by XPS. We also investigate the effect of an external electrical field on the concentration of oxygen vacancies at the Al/ZnO interface. We find that the resistive switching can be attributed to the migration of oxygen vacancies driven by the electrical field, accompanied by adsorption/desorption of oxygen molecules at the Al/ZnO interface. This process gives rise to the formation of a dipole layer, which modulates the injection barrier, and is responsible for switching the resistance state of the memory device.
Relation between Debye temperature and energy band gap of semiconductors
Authors: Ullrich Bruno , Bhowmick Mithun , Xi Haowen
Published: April 2017

The work addresses an unresolved topic in solid-state physics, i.e., the dependence of the Debye temperature (TD) on the energy band gap (Eg) of semiconducting materials. The systematic calculation of TD by using the ratio of sound velocity and lattice constant from the literature resulted in the relation TD∝exp(Eg). The exponential relationship is confirmed by a theoretical model based on the microscopic analysis of the electrical conductivity in metals and semiconductors.
Investigation into the Use of a Diaminodihydroxyaryl Derivative of Ethylenediaminetetraacetic Acid (DAHA-EDTA) for Cu-64 PET Imaging and Radioimmunotherapy
Authors: Ramli Martalena , Schmidt Peter F. , Di Bartolo Nadine , Smith Suzanne V.
Published: April 2017

A diaminodihydroxyaryl derivative of ethylenediaminetetraacetic acid (DAHA-EDTA) was synthesised in two steps and evaluated for Cu-64 radiolabelling of the B72.3 antibody. The ligand complexes Cu-64 rapidly in a pH range 4 to 7. The Cu-64 complex of the parent species N,N′-bis(carboxymethyl)-N,N′-bis(2-hydroxyacetanilido)-1,2-diaminoethane (DHA-EDTA) shows good stability in serum at 37°C for up to 72 h. Conjugation of the Cu-64-DAHA-EDTA to the B72.3 antibody was achieved using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the activating agent. The reaction conditions were optimized for protein concentration and molar ratio of Cu-64-DAHA-EDTA and EDC to antibody. The specific activity of the final [Cu-64-DAHA-EDTA]-B72.3 product was 49 MBq mg−1 at the end of synthesis. The biodistribution of [Cu-64-DAHA-EDTA]-B72.3 in LS174t tumour-bearing nude mice was monitored over a 24 h period. Maximum tumour uptake (25.8 ± 7.5 % ID g−1) was achieved at 16 h and maintained at 24 h (21.6 ± 1.8 % ID g−1). Rapid clearance of the [Cu-64-DAHA-EDTA]-B72.3 from the blood resulted in good tumour-to-blood ratios (≈ 3.3) within a shorter period (6 h) than previously reported with B72.3 whole antibody and the LS174t tumour bearing nude mouse model.
Plugging in microbial metabolism for industrial applications
Authors: Bell Carolyn A , Franks Ashley E
Published: April 2017

The ability of electric microbes to electrically interact with electrodes is opening up a number of possibilities with industrial applications. Microbes are able to utilise the electrode as an electron source to reduce CO2 for the production of organic compounds directly or produce H2 as a reducing equivalent for partner microbes for the production of commodity chemicals. Electrodes can also allow redox unbalanced fermentation processes to occur through the addition or subtraction of reducing equivalents that remove bottle necks in these pathways. Electrodes are also providing a physical refuge for electric microbes to maintain anaerobic fermenter stability. It can be expected that the role for electric microbes will continued to be expanded as part of industrial applications in the future.
Supplementation of culture medium with L-carnitine improves the development and cryotolerance of in vitro-produced porcine embryos
Authors: Lowe J. L. , Bartolac L. K. , Bathgate R. , Grupen C. G.
Published: April 2017

Porcine oocytes and embryos contain substantial amounts of lipid, with little known regarding its metabolic role during development. This study investigated the role of lipid metabolism and the interaction between carbohydrate and lipid substrates in porcine embryos. Following in vitro fertilisation, presumptive zygotes were transferred to culture medium supplemented with L-carnitine, a co-factor required for the metabolism of fatty acids. In porcine zygote medium-3 (PZM-3), which contains pyruvate and lactate, 3 mM L-carnitine was the only dose that improved cleavage rates compared with the control. In the absence of carbohydrates, all doses of L-carnitine from 1.5 to 12 mM increased cleavage rates compared with the control. Culture in a PZM-3-based sequential media system (Days 0–3: pyruvate and lactate; Days 4–7: glucose) significantly increased blastocyst cell numbers compared with culture in standard PZM-3. Supplementing PZM-3 with 3 mM L-carnitine produced blastocysts with cell numbers equivalent to those obtained in the sequential media system. After vitrification, the post-warming survival rates of blastocysts obtained in media supplemented with 3 mM L-carnitine were significantly greater than those of blastocysts obtained in standard PZM-3. In conclusion, L-carnitine supplementation improved embryo development when the medium contained pyruvate and lactate or was lacking carbohydrates completely, indicating a role for fatty-acid metabolism when the embryo’s requirements for carbohydrates are not adequately met.
Social interactions among grazing reef fish drive material flux in a coral reef ecosystem
Authors: Gil Michael A. , Hein Andrew M.
Published: April 2017

Significance

Social behaviors pervade natural ecosystems, but their effects on ecosystem processes have been difficult to measure. Here, we demonstrate that coral reef fish base decisions to feed on algae or flee from predators on the density and actions of other fish in the landscape, inducing strong temporal correlations in foraging behavior. Using field experiments and a modeling framework, we show that these behavioral interactions can strongly affect the ecological function of reef fish, including the amount of algae fish consume, and the resulting rate at which fish move energy and materials through the reef ecosystem. More generally, our results illustrate that behavioral correlations can exert a dominant effect on ecosystem processes.
Cyclooxygenase-derived proangiogenic metabolites of epoxyeicosatrienoic acids
Authors: Rand Amy A. , Barnych Bogdan , Morisseau Christophe , Cajka Tomas , Lee Kin Sing Stephen , Panigrahy Dipak , Hammock Bruce D.
Published: April 2017

Significance

This study furthers our understanding of epoxyeicosatrienoic acid metabolism by cyclooxygenase (COX) enzymes as a physiologically relevant metabolic pathway, producing signaling molecules that are angiogenic. It explains, in part, why inhibiting the soluble epoxide hydrolase (sEH) in some systems is angiogenic whereas combining sEH inhibition with COX inhibition is dramatically antiangiogenic, which in turn may suppress tumor growth.
PIK3CA
mutant tumors depend on oxoglutarate dehydrogenase
Authors: Ilic Nina , Birsoy Kıvanç , Aguirre Andrew J. , Kory Nora , Pacold Michael E. , Singh Shambhavi , Moody Susan E. , DeAngelo Joseph D. , Spardy Nicole A. , Freinkman Elizaveta , Weir Barbara A. , Tsherniak Aviad , Cowley Glenn S. , Root David E. , Asara John M. , Vazquez Francisca , Widlund Hans R. , Sabatini David M. , Hahn William C.
Published: April 2017

Significance

Oncogenic lesions give rise to genotype-specific dependencies in tumors by altering cell physiology. Understanding how oncogenes drive cell transformation will therefore help identify strategies to target tumors harboring these mutations. Although targeting certain oncogenes has led to clinical responses in some cases, PIK3CA inhibition has been disappointing to date. Here, we show that cell proliferation and tumor growth of
PIK3CA
mutant cancers is inhibited by suppression 2-oxoglutarate dehydrogenase, which leads to increased metabolite 2-oxoglutarate (2OG) levels. Elevated 2OG affects the function of the malate–aspartate shuttle, which is important because of the glycolytic nature of these cancers. This work provides novel insights into how mutant PIK3CA drives tumor proliferation and identifies a metabolic dependency that can be exploited in these cancers.
Salting our freshwater lakes
Authors: Dugan Hilary A. , Bartlett Sarah L. , Burke Samantha M. , Doubek Jonathan P. , Krivak-Tetley Flora E. , Skaff Nicholas K. , Summers Jamie C. , Farrell Kaitlin J. , McCullough Ian M. , Morales-Williams Ana M. , Roberts Derek C. , Ouyang Zutao , Scordo Facundo , Hanson Paul C. , Weathers Kathleen C.
Published: April 2017

Significance

In lakes, chloride is a relatively benign ion at low concentrations but begins to have ecological impacts as concentrations rise into the 100s and 1,000s of mg L
−1
. In this study, we investigate long-term chloride trends in 371 freshwater lakes in North America. We find that in Midwest and Northeast North America, most urban lakes and rural lakes that are surrounded by >1% impervious land cover show increasing chloride trends. Expanding on this finding, thousands of lakes in these regions are at risk of long-term salinization. Keeping lakes “fresh” is critically important for protecting the ecosystem services freshwater lakes provide, such as drinking water, fisheries, recreation, irrigation, and aquatic habitat.
CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel
Authors: James Zachary M. , Borst Andrew J. , Haitin Yoni , Frenz Brandon , DiMaio Frank , Zagotta William N. , Veesler David
Published: April 2017

Significance

Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood. We used cryoEM to determine the structure of an intact CNG channel, revealing a conformation that may represent a functional state of this channel family not captured in previous studies.
Proteolytic control of the mitochondrial calcium uniporter complex
Authors: Tsai Chen-Wei , Wu Yujiao , Pao Ping-Chieh , Phillips Charles B. , Williams Carole , Miller Christopher , Ranaghan Matthew , Tsai Ming-Feng
Published: April 2017

Significance

Mitochondrial Ca
2+
regulates several basic biological functions, including the efficiency of mitochondrial ATP production and the onset of mitochondria-mediated cell death. Ca
2+
uptake into mitochondria is mediated by the “mitochondrial calcium uniporter,” a multisubunit Ca
2+
channel complex made of four proteins: MCU, EMRE, MICU1, and MICU2. This work reveals a proteolytic pathway that maintains stoichiometrically balanced MCU and EMRE levels in the inner mitochondrial membrane. Without this mechanism, uniporter subunits can assemble into a dysfunctional subcomplex that perturbs mitochondrial Ca
2+
homeostasis by constitutively loading Ca
2+
into the matrix. The results provide new insights into the regulation of the uniporter function crucial for multicellular organisms to handle the highly dynamic intracellular Ca
2+
signaling network.
Incidence, aetiology and prevention of musculoskeletal injuries in volleyball: A systematic review of the literature
Authors: Kilic O. , Maas M. , Verhagen E. , Zwerver J. , Gouttebarge V.
Published: April 2017

Currently, there is no overview of the incidence and (volleyball‐specific) risk factors of musculoskeletal injuries among volleyball players, nor any insight into the effect of preventive measures on the incidence of injuries in volleyball. This study aimed to review systematically the scientific evidence on the incidence, prevalence, aetiology and preventive measures of volleyball injuries. To this end, a highly sensitive search strategy was built based on two groups of keywords (and their synonyms). Two electronic databases were searched, namely Medline (biomedical literature) via Pubmed, and SPORTDiscus (sports and sports medicine literature) via EBSCOhost. The results showed that ankle, knee and shoulder injuries are the most common injuries sustained while playing volleyball. Results are presented separately for acute and overuse injuries, as well as for contact and non‐contact injuries. Measures to prevent musculoskeletal injuries, anterior knee injuries and ankle injuries were identified in the scientific literature. These preventive measures were found to have a significant effect on decreasing the occurrence of volleyball injuries (for instance on ankle injuries with a reduction from 0.9 to 0.5 injuries per 1000 player hours). Our systematic review showed that musculoskeletal injuries are common among volleyball players, while effective preventive measures remain scarce. Further epidemiological studies should focus on other specific injuries besides knee and ankle injuries, and should also report their prevalence and not only the incidence. Additionally, high‐quality studies on the aetiology and prevention of shoulder injuries are lacking and should be a focus of future studies.
Survival processing eliminates collaborative inhibition
Authors: Reysen Matthew B , Bliss Heather , Baker Melissa A
Published: April 2017

The present experiments examined the effect of processing words for their survival value, relevance to moving and pleasantness on participants’ free recall scores in both nominal groups (non-redundant pooled individual scores) and collaborative dyads. Overall, participants recalled more words in the survival processing conditions than in the moving and pleasantness processing conditions. Furthermore, nominal groups in both the pleasantness condition (Experiment 1) and the moving and pleasantness conditions (Experiment 2) recalled more words than collaborative groups, thereby replicating the oft-observed effect of collaborative inhibition. However, processing words for their survival value appeared to eliminate the deleterious effects of collaborative remembering in both Experiments 1 and 2. These results are discussed in the context of the retrieval strategy disruption hypothesis and the effects of both expertise and collaborative skill on group remembering.
BioCIDER: a Contextualisation InDEx for biological Resources discovery
Authors: Horro Carlos , Cook Martin , Attwood Teresa K , Brazas Michelle D , Hancock John M , Palagi Patricia , Corpas Manuel , Jimenez Rafael
Published: April 2017

The vast, uncoordinated proliferation of bioinformatics resources (databases, software tools, training materials etc.) makes it difficult for users to find them. To facilitate their discovery, various services are being developed to collect such resources into registries. We have developed BioCIDER, which, rather like online shopping ‘recommendations’, provides a contextualization index to help identify biological resources relevant to the content of the sites in which it is embedded.

Availability and Implementation

BioCIDER (www.biocider.org) is an open-source platform. Documentation is available online (https://goo.gl/Klc51G), and source code is freely available via GitHub (https://github.com/BioCIDER). The BioJS widget that enables websites to embed contextualization is available from the BioJS registry (http://biojs.io/). All code is released under an MIT licence.
Multisensory Integration in Cochlear Implant Recipients
Authors: Stevenson Ryan A. , Sheffield Sterling W. , Butera Iliza M. , Gifford René H. , Wallace Mark T.
Published: April 2017

Speech perception is inherently a multisensory process involving integration of auditory and visual cues. Multisensory integration in cochlear implant (CI) recipients is a unique circumstance in that the integration occurs after auditory deprivation and the provision of hearing via the CI. Despite the clear importance of multisensory cues for perception, in general, and for speech intelligibility, specifically, the topic of multisensory perceptual benefits in CI users has only recently begun to emerge as an area of inquiry. We review the research that has been conducted on multisensory integration in CI users to date and suggest a number of areas needing further research. The overall pattern of results indicates that many CI recipients show at least some perceptual gain that can be attributable to multisensory integration. The extent of this gain, however, varies based on a number of factors, including age of implantation and specific task being assessed (e.g., stimulus detection, phoneme perception, word recognition). Although both children and adults with CIs obtain audiovisual benefits for phoneme, word, and sentence stimuli, neither group shows demonstrable gain for suprasegmental feature perception. Additionally, only early-implanted children and the highest performing adults obtain audiovisual integration benefits similar to individuals with normal hearing. Increasing age of implantation in children is associated with poorer gains resultant from audiovisual integration, suggesting a sensitive period in development for the brain networks that subserve these integrative functions, as well as length of auditory experience. This finding highlights the need for early detection of and intervention for hearing loss, not only in terms of auditory perception, but also in terms of the behavioral and perceptual benefits of audiovisual processing. Importantly, patterns of auditory, visual, and audiovisual responses suggest that underlying integrative processes may be fundamentally different between CI users and typical-hearing listeners. Future research, particularly in low-level processing tasks such as signal detection will help to further assess mechanisms of multisensory integration for individuals with hearing loss, both with and without CIs.
The coccyx in clinical medicine
Authors: Protzer Lauren , Seligson David , Doursounian Levon
Published: April 2017

Coccydynia, or pain in the coccyx, is a common and important cause of impaired quality of life that can appear in all medical specialties. Usually caused by trauma, whether external, internal, or by microtrauma from perineal pressure from obesity, many patients heal with conservative modalities at home. When they do come to a physician, the diagnosis can be made from physical examination and dynamic radiographs showing luxation or subluxation of the coccyx. Initial treatment begins with a coccygeal or doughnut cushion, heat, ice, and nonsteroidal anti-inflammatory medications. Physical therapy and manual manipulation may also be of benefit. If there is no improvement, an MRI should be obtained to rule out other etiologies including chordomas. For refractory cases, steroid injections or ganglion impar blocks are appropriate. As a last resort, a coccygectomy or surgical removal of a coccyx may be in order. Most patients, with thoughtful, professional help are able to return to their baseline health and live without coccydynia.
Simultaneous Bilateral Hip Arthroscopy in Adolescent Athletes With Symptomatic Femoroacetabular Impingement
Authors: McConkey Mark O. , Chadayammuri Vivek , Garabekyan Tigran , Mayer Stephanie W. , Kraeutler Matthew J. , Mei-Dan Omer
Published: April 2017

Background:

Femoroacetabular impingement represents a common cause of hip pain in adolescents. The purpose of the present study was to evaluate the safety and efficacy of simultaneous bilateral hip arthroscopy for bilateral symptomatic femoroacetabular impingement in adolescent athletes.

Methods:

Clinical data were collected in a prospective database on patients who underwent unilateral or simultaneous bilateral hip arthroscopy and included complications, reoperation rate, and return to play time. Differences in International Hip Outcome Tool (iHOT)-12 scores according to hip side and postoperative follow-up time (preoperative, 1.5, 3, 6, 12, and 24 mo) were evaluated using a 2×6 repeated-measures analysis of variance with post hoc repeated-measures 1-way analysis of variance and Bonferroni-corrected paired t tests.

Results:

In total, 24 patients (36 hips) were studied, of whom 12 underwent simultaneous bilateral hip arthroscopy (24 hips) and a case-matched control group of 12 patients underwent unilateral hip arthroscopy. There were 5 males in each group (41.7%). Average age was 15.7 and 16.5 years in the bilateral and unilateral groups, respectively. No patients were lost to follow-up. In the bilateral group, a significant increase in mean iHOT-12 score was observed between 1.5- and 3-month follow-up (61.8 vs. 82.8, respectively; P=0.003), and 6-, 12-, and 24-month follow-up (91.4, 95.1, and 96.6, respectively, P=0.004). At all follow-up times, there were no significant differences in mean iHOT-12 scores or other outcome measures between bilateral and unilateral cohorts. Time to return to preinjury level of activity was similar between the bilateral and unilateral groups (4.7 vs. 4.9 mo, respectively; P=0.40). One transient lateral femoral cutaneous nerve palsy occurred in each group, though no other complications were documented. No patients required revision surgery by latest follow-up.

Conclusions:

Bilateral simultaneous hip arthroscopy is safe and reproducible in adolescent athletes, achieving equivalent outcomes, and similar rehabilitation time when compared with unilateral surgery.

Level of Evidence:

Level II—therapeutic study.
Simultaneous Keratolimbal Autograft and Penetrating Autokeratoplasty: A Single-Stage Procedure to Restore Monocular Vision of a Blind Patient With Limbal Stem Cell Deficiency
Authors: Jarade Elias , Amro Mazen , Haydar Ali A. , Hemade Adib
Published: April 2017

Purpose:

To describe the technique of simultaneous keratolimbal autograft and penetrating autokeratoplasty to restore monocular vision of a blind patient with limbal stem cell deficiency (LSCD).

Methods:

A patient with acquired monocular vision due to loss of the left eye owing to LSCD postblast injury presented with acute loss of vision in the right eye due to central retinal artery occlusion. Simultaneous keratolimbal autograft and penetrating autokeratoplasty were performed in attempt to restore his vision in the left eye.

Results:

Postoperatively, the anterior chamber was well formed along with mild graft edema on day 1. Topo-guided suture removal was started at 4 months. The graft maintained clear transparency at 1-year follow-up, and the best-corrected visual acuity improved from hand movement to 20/50.

Conclusions:

Keratolimbal autograft and penetrating autokeratoplasty, as a one-stage procedure, proved to be effective in restoring monocular vision in a patient with LSCD.
Influence of genetic variations in the SOD1 gene on the development of ascites and spontaneous bacterial peritonitis in decompensated liver cirrhosis
Authors: Schwab Sebastian , Lehmann Jennifer , Lutz Philipp , Jansen Christian , Appenrodt Beate , Lammert Frank , Strassburg Christian P. , Spengler Ulrich , Nischalke Hans-Dieter , Trebicka Jonel
Published: April 2017

Background

The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated.

Patients and methods

Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing liver transplantation. In addition, 344 cirrhotic patients with ascites were analyzed in a cohort of 521 individuals in terms of the relationship of these polymorphisms with spontaneous bacterial peritonitis (SBP).

Results

Although rs3844942 showed no associations with complications of cirrhosis, we observed a significant association between rs1041740 and the presence of ascites and SBP in the discovery cohort of patients with cirrhosis. Importantly, the association with SBP was not confirmed in the validation cohort of patients with ascites. By contrast, a trend toward lower SBP rates was observed in carriers of rs1041740. In this cohort, rs1041740 was not associated with survival.

Conclusion

These data suggest a complex role of SOD1 in different processes leading to complications of liver cirrhosis. rs1041740 might be associated with the development of ascites and possibly plays a role in SBP once ascites has developed.
Increased Epicardial Fat Thickness in Sudden Death From Stable Coronary Artery Atherosclerosis
Authors: Fuller Belinda , Garland Jack , Anne Sravan , Beh Raymond , McNevin Dennis , Tse Rexson
Published: April 2017

Background

Sudden death from stable coronary artery atherosclerosis (SCAA) is well recognized. However, individuals can have ischemic heart disease or coronary artery atherosclerosis but die of noncardiac causes. Recently, it has been recognized that increased epicardial fat is detrimental to normal heart function. We hypothesize that individuals who die of SCAA have increased epicardial fat.

Aim

The aim of this study was to investigate whether there is an increase in epicardial fat in individuals who suddenly died of SCAA.

Methods

This was a 1-year retrospective study comparing the average epicardial fat thickness using postmortem computed tomography scan between individuals who suddenly died of SCAA (SCAA group) with individuals who primarily died of natural noncardiac causes but had established ischemic heart disease or significant coronary artery atherosclerosis (NCC group).

Results

Average epicardial fat thickness was significantly higher in the SCAA group (8 ± 2 mm) than in the NCC group (6 ± 2 mm, P = 0.008).

Conclusions

Individuals who die of SCAA appear to have higher epicardial fat thickness. The increase in epicardial fat may have an additional detrimental effect to the heart predisposing sudden death in individuals with coronary artery atherosclerosis.
The Ebola outbreak, 2013–2016: old lessons for new epidemics
Authors: Coltart Cordelia E. M. , Lindsey Benjamin , Ghinai Isaac , Johnson Anne M. , Heymann David L.
Published: April 2017

Ebola virus causes a severe haemorrhagic fever in humans with high case fatality and significant epidemic potential. The 2013–2016 outbreak in West Africa was unprecedented in scale, being larger than all previous outbreaks combined, with 28 646 reported cases and 11 323 reported deaths. It was also unique in its geographical distribution and multicountry spread. It is vital that the lessons learned from the world's largest Ebola outbreak are not lost. This article aims to provide a detailed description of the evolution of the outbreak. We contextualize this outbreak in relation to previous Ebola outbreaks and outline the theories regarding its origins and emergence. The outbreak is described by country, in chronological order, including epidemiological parameters and implementation of outbreak containment strategies. We then summarize the factors that led to rapid and extensive propagation, as well as highlight the key successes, failures and lessons learned from this outbreak and the response.

This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
Characterizing risk of Ebola transmission based on frequency and type of case–contact exposures
Authors: Skrip Laura A. , Fallah Mosoka P. , Gaffney Stephen G. , Yaari Rami , Yamin Dan , Huppert Amit , Bawo Luke , Nyenswah Tolbert , Galvani Alison P.
Published: April 2017

During the initial months of the 2013–2016 Ebola epidemic, rapid geographical dissemination and intense transmission challenged response efforts across West Africa. Contextual behaviours associated with increased risk of exposure included travel to high-transmission settings, caring for sick and preparing the deceased for traditional funerals. Although such behaviours are widespread in West Africa, high-transmission pockets were observed. Superspreading and clustering are typical phenomena in infectious disease outbreaks, as a relatively small number of transmission chains are often responsible for the majority of events. Determining the characteristics of contacts at greatest risk of developing disease and of cases with greatest transmission potential could therefore help curb propagation of infection. Our analysis of contact tracing data from Montserrado County, Liberia, suggested that the probability of transmission was 4.5 times higher for individuals who were reported as having contact with multiple cases. The probability of individuals developing disease was not significantly associated with age or sex of their source case but was higher when they were in the same household as the infectious case. Surveillance efforts for rapidly identifying symptomatic individuals and effectively messaged campaigns encouraging household members to bring the sick to designated treatment centres without administration of home care could mitigate transmission.

This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
Command and control of Sierra Leone's Ebola outbreak response: evolution of the response architecture
Authors: Ross Emma
Published: April 2017

Management, coordination and logistics were critical for responding effectively to the Ebola outbreak in Sierra Leone, and the duration of the epidemic provided a rare opportunity to study the management of an outbreak that endured long enough for the response to mature. This qualitative study examines the structures and systems used to manage the response, and how and why they changed and evolved. It also discusses the quality of relationships between key responders and their impact. Early coordination mechanisms failed and the President took operational control away from the Ministry of Health and Sanitation and established a National Ebola Response Centre, headed by the Minister of Defence, and District Ebola Response Centres. British civilian and military personnel were deeply embedded in this command and control architecture and, together with the United Nations Mission for Ebola Emergency Response lead, were the dominant coordination partners at the national level. Coordination, politics and tensions in relationships hampered the response, but as the response mechanisms matured, coordination improved and rifts healed. Simultaneously setting up new organizations, processes and plans as well as attempting to reconcile different cultures, working practices and personalities in such an emergency was bound to be challenging.

This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.
Electrochemical measurement of acetylcholine in the dorsolateral prefrontal cortex: A technical report
Authors: Vartak Devavrat , van der Togt Chris , van Vugt Bram , Roelfsema Pieter R.
Published: April 2017

Ever since the discovery of acetylcholine in 1913, its role as neuromodulator has been extensively studied in a variety of model systems. These previous studies revealed that acetylcholine is of critical importance for several cognitive functions including attention, learning and memory. In spite of these previous findings, it has proven difficult to determine the amount of acetylcholine that is released during cognitive tasks with sub-second temporal resolution. One method that might be used to measure acetylcholine release is the use of an enzyme-coupled amperometric sensor, which has been suggested to measure acetylcholine with high sensitivity, selectivity and relatively high temporal resolution (< 1 second). In the present study, we have tried to adapt the technique developed in the rodent model system by Parikh and colleagues1,2for use in non-human primates. We aimed to measure in-vivo levels of acetylcholine in the macaque dorsolateral prefrontal cortex while the monkey performed an attention demanding curve-tracing task3,4. We report that our attempts to measure acetylcholine using amperometry in an awake behaving macaque monkey proved difficult and tedious and that our results are inconsistent and prone to noise. In the discussion, we will outline the challenges that will need to be addressed to use this technique in non-human primates and hope that our observations inspire solutions to help future research on the role of this important neurotransmitter.
The sequence of a male-specific genome region containing the sex determination switch inAedes aegypti
Authors: Turner Joe , Krishna Ritesh , Van’t Hof Arjen E. , Sutton Elizabeth R. , Matzen Kelly , Darby Alistair C.
Published: April 2017

Aedes aegyptiis the principal vector of several important arboviruses. Among the methods of vector control to limit transmission of disease are genetic strategies that involve the release of sterile or genetically modified non-biting males (Alphey 2014), which has generated interest in manipulating mosquito sex ratios (Gilleset al.2014; Adelman and Tu 2016). Sex determination inAe. aegyptiis controlled by a non-recombining Y chromosome-like region called the M locus (Craiget al. 1960), yet characterisation of this locus has been thwarted by the repetitive nature of the genome (Hallet al.2015). In 2015, an M locus gene named Nix was identified that displays the qualities of a sex determination switch (Hallet al.2015). With the use of a whole-genome BAC library, we amplified and sequenced a ~200kb region containing this male-determining gene. In this study, we show that Nix is comprised of two exons separated by a 99kb intron, making it an unusually large gene. The intron sequence is highly repetitive and exhibits features in common with old Y chromosomes, and we speculate that the lack of recombination at the M locus has allowed the expansion of repeats in a manner characteristic of a sex-limited chromosome, in accordance with proposed models of sex chromosome evolution in insects.
Looking into Pandora’s Box: The Content ofSci-Huband its Usage
Authors: Greshake Bastian
Published: April 2017

Despite the growth of Open Access, illegally circumventing paywalls to access scholarly publications is becoming a more mainstream phenomenon. The web serviceSci-Hubis amongst the biggest facilitators of this, offering free access to around 62 million publications. So far it is not well studied how and why its users are accessing publications throughSci-Hub. By utilizing the recently released corpus ofSci-Huband comparing it to the data of ˜28 million downloads done through the service, this study tries to address some of these questions. The comparative analysis shows that both the usage and complete corpus is largely made up of recently published articles, with users disproportionately favoring newer articles and 35% of downloaded articles being published after 2013. These results hint that embargo periods before publications become Open Access are frequently circumnavigated using Guerilla Open Access approaches likeSci-Hub. On a journal level, the downloads show a bias towards some scholarly disciplines, especially Chemistry, suggesting increased barriers to access for these. Comparing the use and corpus on a publisher level, it becomes clear that only 11% of publishers are highly requested in comparison to the baseline frequency, while 45% of all publishers are significantly less accessed than expected. Despite this, the oligopoly of publishers is even more remarkable on the level of content consumption, with 80% of all downloads being published through only 9 publishers. All of this suggests thatSci-Hubis used by different populations and for a number of different reasons, and that there is still a lack of access to the published scientific record. A further analysis of these openly available data resources will undoubtedly be valuable for the investigation of academic publishing.