bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-Fuel Simulation Near Nozzle Outlet of Fuel Injector During Closing Valve
Authors: Ishii Eiji , Yoshimura Kazuki , Yasukawa Yoshihito , Ehara Hideharu
Published: March 2016

Late fuel during closing of the valve of a fuel injector and fuel films stuck on the wall around the nozzle outlets are sources of particulate matters (PM). In this study, we focused on the effects of the valve motions on the late fuel and the fuel films stuck on the walls around the nozzle outlets. We previously developed a particle/grid hybrid method: fuel flows within the flow paths of fuel injectors were simulated by a front capturing method, and liquid-column breakup at the nozzle outlets was mainly simulated by a particle method. The velocity at the inlet boundary of a fuel injector was controlled in order to affect the valve motions on the late-fuel behavior. The simulated late fuel broke up with surface tension around the time of zero-stroke position of the valve, then liquid columns and coarse droplets formed after the bounds of the valve, and finally only coarse droplets were left. We found that the late fuel was generated by low-speed fuel-flows through the nozzles during the bounds of the valve. The effect of the bounds of the valve on the fuel films stuck on the wall around the nozzle outlets was also studied with a simulation that removed the bounds of the valve. The volume of the fuel films stuck on the wall of the nozzle outlets decreased without the bounds of the valve.
Determination of Flow Units in Carbonate Reservoir With Multiscale Karst Morphology
Authors: Yang Yang , Liu Huiqing , Wang Jing , Zhang Zhaoxiang , Chen Qingyuan , Cheng Hong
Published: March 2016

The Tahe reservoir, one of the largest scale carbonate reservoirs in western China, has very special cavities and fractures. The size of the cavities ranges from millimeter to meter scale, and the size of the fractures ranges from hundreds micrometers to millimeters scale. The length of some cavities can even reach kilometers. However, based on views of core testing results, there is insignificant flow in the rock matrix. This paper introduces a new and refined method to determine flow units in such Karst carbonate reservoirs. Based on fractal theory, fluid flow patterns can be divided into three types by using production data of the Tahe reservoir. Through porosity and permeability statistics of production layers on the established geological model, flow boundaries of different flow patterns were proposed. Flow units were classified in terms of the flow boundaries. As for refined flow units, subcategory flow units were determined by three graphical tools: the limit of dynamic synthesis coefficient (DSCL) method, modified flow coefficient (MS1 and MS2, which are derived by the Forchheimer equation) curve, and the stratigraphic modified Lorenz plot (SMLP). All the parameters of graphical tools help to reconcile geology to fluid flow by illustrating the important link between geology, petrophysics, and reservoir engineering. The use of this technique is illustrated with data from a specific block of the Tahe reservoir.
Small-Volume Fabrication of a 144-Cell Assembly for High-Concentrating Photovoltaic Receivers
Authors: Micheli Leonardo , Fernández Eduardo F. , Sarmah Nabin , Senthilarasu S. , Reddy K. S. , Mallick Tapas K.
Published: March 2016

Concentrating photovoltaic (CPV) is a solution that is gaining attention worldwide as a potential global player in the future energy market. Despite the impressive development in terms of CPV cell efficiency recorded in the last few years, a lack of information on the module's manufacturing is still registered among the documents available in literature. This work describes the challenges faced to fabricate a densely packed cell assembly for 500× CPV applications. The reasons behind the choice of components, materials, and processes are highlighted, and all the solutions applied to overtake the problems experienced after the prototype's production are reported. This article explains all the stages required to achieve a successful fabrication, proven by the results of quality tests and experimental investigations conducted on the prototype. The reliability of the components and the interconnectors is successfully assessed through standard mechanical destructive tests, and an indoor characterization is conducted to investigate the electrical performance. The fabricated cell assembly shows a fill factor as high as 84%, which proves the low series resistance and the lack of mismatches. The outputs are compared with those of commercial assemblies. A cost breakdown is reported and commented: a cost of $0.79/Wp has been required to fabricate each of the cell assembly described in this paper. This value has been found to be positively affected by the economy of scale: a larger number of assemblies produced would have reduced it by 17%.
Maximum von Mises Stress and Its Location in Trilayer Materials in Contact
Authors: Yu Chengjiao , Wang Zhanjiang , Liu Geng , Keer Leon M. , Jane Wang Q.
Published: March 2016

Trilayer materials consisting of a functional outer layer on a substrate containing one intermediate layer are widely used in data-processing devices, biomedical components, and mechanical elements. The recent analytical frequency response functions (FRFs) derived by the authors' group for the contact of multilayer materials lead to the novel deterministic modeling of frictionless and frictional contact involving a trilayer material system designed with various thickness and elastic property combinations. Displacements and stresses for point contacts are calculated effectively by employing the discrete-convolution and fast Fourier transform (FFT) method based on the influence coefficients obtained from the analytical FRFs. The maximum von Mises stress and its location, which are critical information for understanding the material contact status, are thoroughly investigated for a wide range of trilayer materials. The results provide an informative guideline for the design of bilayer coatings without contact failure.
Parameter Identification of Ship Maneuvering Model Based on Support Vector Machines and Particle Swarm Optimization
Authors: Luo Weilin , Guedes Soares C. , Zou Zaojian
Published: March 2016

Combined with the free-running model tests of KVLCC ship, the system identification (SI) based on support vector machines (SVM) is proposed for the prediction of ship maneuvering motion. The hydrodynamic derivatives in an Abkowitz model are determined by the Lagrangian factors and the support vectors in the SVM regression model. To obtain the optimized structural factors in SVM, particle swarm optimization (PSO) is incorporated into SVM. To diminish the drift of hydrodynamic derivatives after regression, a difference method is adopted to reconstruct the training samples before identification. The validity of the difference method is verified by correlation analysis. Based on the Abkowitz mathematical model, the simulation of ship maneuvering motion is conducted. Comparison between the predicted results and the test results demonstrates the validity of the proposed methods in this paper.
Study of Maneuverability of Container Ship With Nonlinear and Roll-Coupled Effects by Numerical Simulations Using RANSE-Based Solver
Authors: Rajita Shenoi R. , Krishnankutty P. , Panneer Selvam R.
Published: March 2016

The examination of maneuvering qualities of a ship is necessary to ensure its navigational safety and prediction of trajectory. The study of maneuverability of a ship is a three-step process, which involves selection of a suitable mathematical model, estimation of the hydrodynamic derivatives occurring in the equation of motion, and simulation of the standard maneuvering tests to determine its maneuvering qualities. This paper reports the maneuvering studies made on a container ship model (S175). The mathematical model proposed by Son and Nomoto (1981, “On Coupled Motion of Steering and Rolling of a High Speed Container Ship,” J. Soc. Nav. Arch. Jpn., 150, pp. 73–83) suitable for the nonlinear roll-coupled steering model for high-speed container ships is considered here. The hydrodynamic derivatives are determined by numerically simulating the planar motion mechanism (PMM) tests in pure yaw and combined sway–yaw mode using an Reynolds-Averaged Navier–Stokes Equations (RANSE)-based computational fluid dynamics (CFD) solver. The tests are repeated with the model inclined at different heel angles to obtain the roll-coupled derivatives. Standard definitive maneuvers like turning tests at rudder angle, 35 deg and 20 deg/20 deg zig-zag maneuvers are simulated using the numerically obtained derivatives and are compared with those obtained using experimental values.
Critical thickness investigation of MBE-grown GaInAs/GaAs and GaAsSb/GaAs heterostructures
Authors: Maros Aymeric , Faleev Nikolai , King Richard R. , Honsberg Christiana B. , Convey Diana , Xie Hongen , Ponce Fernando A.
Published: March 2016

GaInAs/GaAs and GaAsSb/GaAs heterostructures were grown by molecular beam epitaxy with different In/Sb compositions and thicknesses in order to obtain samples with different amounts of initial strain. High resolution x-ray diffraction was used to extract the alloys composition, specify the presence of dislocations, and determine the extent of relaxation while transmission electron microscopy and x-ray topography were used to observe these dislocations and characterize their type and density. The onset for the formation of misfit dislocations was found to be in agreement with the equilibrium theory. However, the films remained coherently strained for thicknesses far beyond this value. The onset for strain relaxation was found by considering the kinetics of plastic deformation using the approach proposed by Tsao and coworkers [Phys. Rev. Lett. 59, 2455 (1987)]. The mechanism of extended defect creation leading to measurable strain relief is described as a multistage process related with the structural stability and metastability of the epitaxial films.
Sputtering of silicon and glass substrates with polyatomic molecular ion beams generated from ionic liquids
Authors: Takeuchi Mitsuaki , Hoshide Yuki , Ryuto Hiromichi , Takaoka Gikan H.
Published: March 2016

The effect of irradiating 1-ethyl-3-methylimidazolium positive (EMIM+) or dicyanamide negative (DCA–) ion beams using an ionic liquid ion source was characterized concerning its sputtering properties for single crystalline Si(100) and nonalkaline borosilicate glass substrates. The irradiation of the DCA– ion beam onto the Si substrate at an acceleration voltage of 4 and 6 kV exhibited detectable sputtered depths greater than a couple of nanometers with an ion fluence of only 1 × 1015 ions/cm2, while the EMIM+ ion beam produced the same depths with an ion fluence 5 × 1015 ions/cm2. The irradiation of a 4 kV DCA– ion beam at a fluence of 1 × 1016 ions/cm2 also yields large etching depths in Si substrates, corresponding to a sputtering yield of Si/DCA– = 10, and exhibits a smoothed surface roughness of 0.05 nm. The interaction between DCA– and Si likely causes a chemical reaction that relates to the high sputtering yield and forms an amorphous C-N capping layer that results in the smooth surface. Moreover, sputtering damage by the DCA– irradiation, which was estimated by Rutherford backscattering spectroscopy with the channeling technique, was minimal compared to Ar+ irradiation at the same condition. In contrast, the glass substrates exhibited no apparent change in surface roughnesses when sputtered by the DCA– irradiation compared to the unirradiated glass substrates.
Automated estimation of the truncation of room impulse response by applying a nonlinear decay model
Authors: Janković Marko , Ćirić Dejan G. , Pantić Aleksandar
Published: March 2016

Noise represents one of the most significant disturbances in measured room impulse responses (RIRs), and it has a potentially large impact on evaluation of the decay parameters. In order to reduce noise effects, various methods have been applied, including truncation of an RIR. In this paper, a procedure for the response truncation based on a model of RIR (nonlinear decay model) is presented. The model is represented by an exponential decay plus stationary noise. Unknown parameters of the model are calculated by an optimization that minimizes the difference between the curve generated by the model and the target one of the response to be truncated. Different curves can be applied in the optimization—absolute value of the RIR, logarithmic decay curve, and Schroeder curve obtained by the backward integration of the RIR. The proposed procedure is tested on various synthesized and measured impulse responses. It is compared with the procedure taken from the literature, often applied in practice.
Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models
Authors: Karuppagounder Saravanan S. , Alim Ishraq , Khim Soah J. , Bourassa Megan W. , Sleiman Sama F. , John Roseleen , Thinnes Cyrille C. , Yeh Tzu-Lan , Demetriades Marina , Neitemeier Sandra , Cruz Dana , Gazaryan Irina , Killilea David W. , Morgenstern Lewis , Xi Guohua , Keep Richard F. , Schallert Timothy , Tappero Ryan V. , Zhong Jian , Cho Sunghee , Maxfield Frederick R. , Holman Theodore R. , Culmsee Carsten , Fong Guo-Hua , Su Yijing , Ming Guo-li , Song Hongjun , Cave John W. , Schofield Christopher J. , Colbourne Frederick , Coppola Giovanni , Ratan Rajiv R.
Published: March 2016

Blocking oxygen-sensing prolyl hydroxylases in the rodent CNS enhances functional recovery after brain hemorrhage.
ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma
Authors: Koschmann Carl , Calinescu Anda-Alexandra , Nunez Felipe J. , Mackay Alan , Fazal-Salom Janet , Thomas Daniel , Mendez Flor , Kamran Neha , Dzaman Marta , Mulpuri Lakshman , Krasinkiewicz Johnathon , Doherty Robert , Lemons Rosemary , Brosnan-Cashman Jacqueline A. , Li Youping , Roh Soyeon , Zhao Lili , Appelman Henry , Ferguson David , Gorbunova Vera , Meeker Alan , Jones Chris , Lowenstein Pedro R. , Castro Maria G.
Published: March 2016

The loss of ATRX impairs DNA repair, promoting glioma growth but enhancing sensitivity to DNA-damaging therapies.
Turning BiKEs into TriKEs to fight cancer
Authors: Dronca Roxana
Published: March 2016

Incorporation of IL-15 into a bispecific antibody recognizing CD16 and CD33 boosted natural killer cells’ survival and activity against acute myeloid leukemia.
Fluid dynamics of disease transmission
Authors: Heldt Thomas
Published: March 2016

Studying the fluid dynamics of violent exhalations might hold the key to a better understanding of disease transmission—and its containment.
Revolutionary Science
Authors: Casadevall Arturo , Fang Ferric C.
Published: March 2016

On rare occasions in the history of science, remarkable discoveries transform human society and forever alter mankind’s view of the world. Examples of such discoveries include the heliocentric theory, Newtonian physics, the germ theory of disease, quantum theory, plate tectonics and the discovery that DNA carries genetic information. The science philosopher Thomas Kuhn famously described science as long periods of normality punctuated by times of crisis, when anomalous observations culminate in revolutionary changes that replace one paradigm with another. This essay examines several transformative discoveries in the light of Kuhn’s formulation. We find that each scientific revolution is unique, with disparate origins that may include puzzle solving, serendipity, inspiration, or a convergence of disparate observations. The causes of revolutionary science are varied and lack an obvious common structure. Moreover, it can be difficult to draw a clear distinction between so-called normal and revolutionary science. Revolutionary discoveries often emerge from basic science and are critically dependent on nonrevolutionary research. Revolutionary discoveries may be conceptual or technological in nature, lead to the creation of new fields, and have a lasting impact on many fields in addition to the field from which they emerge. In contrast to political revolutions, scientific revolutions do not necessarily require the destruction of the previous order. For humanity to continue to benefit from revolutionary discoveries, a broad palette of scientific inquiry with a particular emphasis on basic science should be supported.
Complex Interplay of the
UL136
Isoforms Balances Cytomegalovirus Replication and Latency
Authors: Caviness Katie , Bughio Farah , Crawford Lindsey B. , Streblow Daniel N. , Nelson Jay A. , Caposio Patrizia , Goodrum Felicia
Published: March 2016

Human cytomegalovirus (HCMV), a betaherpesvirus, persists indefinitely in the human host through poorly understood mechanisms. The
UL136
gene is carried within a genetic locus important to HCMV latency termed the
UL133
/
8
locus, which also carries
UL133
,
UL135
, and
UL138
. Previously, we demonstrated that
UL136
is expressed as five protein isoforms ranging from 33-kDa to 19-kDa, arising from alternative transcription and, likely, translation initiation mechanisms. We previously showed that the
UL136
isoforms are largely dispensable for virus infection in fibroblasts, a model for productive virus replication. In our current work,
UL136
has emerged as a complex regulator of HCMV infection in multiple contexts of infection relevant to HCMV persistence: in an endothelial cell (EC) model of chronic infection, in a CD34
+
hematopoietic progenitor cell (HPC) model of latency, and in an
in vivo
NOD-
scid
IL2Rγ
c
null
humanized (huNSG) mouse model for latency. The 33- and 26-kDa isoforms promote replication, while the 23- and 19-kDa isoforms suppress replication in ECs, in CD34
+
HPCs, and in huNSG mice. The role of the 25-kDa isoform is context dependent and influences the activity of the other isoforms. These isoforms localize throughout the secretory pathway, and loss of the 33- and 26-kDa
UL136
isoforms results in virus maturation defects in ECs. This work reveals an intriguing functional interplay between protein isoforms that impacts virus replication, latency, and dissemination, contributing to the overall role of the
UL133
/
8
locus in HCMV infection.

IMPORTANCE
The persistence of DNA viruses, and particularly of herpesviruses, remains an enigma because we have not completely defined the viral and host factors important to persistence. Human cytomegalovirus, a herpesvirus, persists in the absence of disease in immunocompetent individuals but poses a serious disease threat to transplant patients and the developing fetus. There is no vaccine, and current therapies do not target latent reservoirs. In an effort to define the viral factors important to persistence, we have studied viral genes with no known viral replication function in contexts important to HCMV persistence. Using models relevant to viral persistence, we demonstrate opposing roles of protein isoforms encoded by the
UL136
gene in regulating latent and replicative states of infection. Our findings reveal an intriguing interplay between
UL136
protein isoforms and define
UL136
as an important regulator of HCMV persistence.
Balance between Coiled-Coil Stability and Dynamics Regulates Activity of BvgS Sensor Kinase in
Bordetella
Authors: Lesne E. , Krammer E.-M. , Dupre E. , Locht C. , Lensink M. F. , Antoine R. , Jacob-Dubuisson F.
Published: March 2016

The two-component system BvgAS controls the expression of the virulence regulon of
Bordetella pertussis
. BvgS is a prototype of bacterial sensor kinases with extracytoplasmic Venus flytrap perception domains. Following its transmembrane segment, BvgS harbors a cytoplasmic Per-Arnt-Sim (PAS) domain and then a predicted 2-helix coiled coil that precede the dimerization-histidine-phosphotransfer domain of the kinase. BvgS homologs have a similar domain organization, or they harbor only a predicted coiled coil between the transmembrane and the dimerization-histidine-phosphotransfer domains. Here, we show that the 2-helix coiled coil of BvgS regulates the enzymatic activity in a mechanical manner. Its marginally stable hydrophobic interface enables a switch between a state of great rotational dynamics in the kinase mode and a more rigid conformation in the phosphatase mode in response to signal perception by the periplasmic domains. We further show that the activity of BvgS is controlled in the same manner if its PAS domain is replaced with the natural α-helical sequences of PAS-less homologs. Clamshell motions of the Venus flytrap domains trigger the shift of the coiled coil’s dynamics. Thus, we have uncovered a general mechanism of regulation for the BvgS family of Venus flytrap-containing two-component sensor kinases.

IMPORTANCE
The two-component system BvgAS of the whooping cough agent
Bordetella pertussis
regulates the virulence factors necessary for infection in a coordinated manner. BvgS is the prototype of a family of sensor kinase proteins found in major bacterial pathogens. When BvgS functions as a kinase,
B. pertussis
is virulent, and the bacterium shifts to an avirulent phase after BvgS senses chemicals that make it switch to phosphatase. Our goal is to decipher the signaling mechanisms of BvgS in order to understand virulence regulation in
Bordetella
, which may lead to new antimicrobial treatments targeting those two-component systems. We discovered that the activity of BvgS is regulated in a mechanical manner. A short region of the protein that precedes the enzymatic domain switches between two states in response to signal perception by other BvgS domains. This switch region is conserved among BvgS homologs, and thus, the regulation uncovered here will likely be relevant for the family.
Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System
Authors: Bhuwan Manish , Arora Naresh , Sharma Ashish , Khubaib Mohd , Pandey Saurabh , Chaudhuri Tapan Kumar , Hasnain Seyed Ehtesham , Ehtesham Nasreen Zafar
Published: March 2016

Mycobacterium tuberculosis
is a leading cause of death worldwide. The
M. tuberculosis
TAT (twin-arginine translocation) protein secretion system is present at the cytoplasmic membrane of mycobacteria and is known to transport folded proteins. The TAT secretion system is reported to be essential for many important bacterial processes that include cell wall biosynthesis. The
M. tuberculosis
secretion and invasion protein RipA has endopeptidase activity and interacts with one of the resuscitation antigens (RpfB) that are expressed during pathogen reactivation. MoxR1, a member of the ATPase family that is associated with various cellular activities, was predicted to interact with RipA based on
in silico
analyses. A bimolecular fluorescence complementation (BiFC) assay confirmed the interaction of these two proteins in HEK293T cells. The overexpression of RipA in
Mycobacterium smegmatis
and copurification with MoxR1 further validated their interaction
in vivo
. Recombinant MoxR1 protein, expressed in
Escherichia coli
, displays ATP-enhanced chaperone activity. Secretion of recombinant RipA (rRipA) protein into the
E. coli
culture filtrate was not observed in the absence of RipA-MoxR interaction. Inhibition of this export system in
M. tuberculosis
, including the key players, will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing.

IMPORTANCE
The virulence mechanism of mycobacteria is very complex. Broadly, the virulence factors can be classified as secretion factors, cell surface components, enzymes involved in cellular metabolism, and transcriptional regulators. The mycobacteria have evolved several mechanisms to secrete its proteins. Here, we have identified one of the virulence proteins of
Mycobacterium tuberculosis
, RipA, possessing peptidoglycan hydrolase activities secreted by the TAT secretion pathway. We also identified MoxR1 as a protein-protein interaction partner of RipA and demonstrated chaperone activity of this protein. We show that MoxR1-mediated folding is critical for the secretion of RipA within the TAT system. Inhibition of this export system in
M. tuberculosis
will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing.
Loss of Multicellular Behavior in Epidemic African Nontyphoidal Salmonella enterica Serovar Typhimurium ST313 Strain D23580
Authors: Singletary Larissa A. , Karlinsey Joyce E. , Libby Stephen J. , Mooney Jason P. , Lokken Kristen L. , Tsolis Renée M. , Byndloss Mariana X. , Hirao Lauren A. , Gaulke Christopher A. , Crawford Robert W. , Dandekar Satya , Kingsley Robert A. , Msefula Chisomo L. , Heyderman Robert S. , Fang Ferric C.
Published: March 2016

Nontyphoidal
Salmonella enterica
serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for
Salmonella
survival outside the host. While these studies have not ruled out zoonotic or other means of transmission, the anthroponotic hypothesis is supported by evidence of extensive genomic decay, a hallmark of host adaptation, in the sequenced ST313 strain D23580. We have identified and demonstrated 2 loss-of-function mutations in D23580, not present in the ST19 strain 14028s, that impair multicellular stress resistance associated with survival outside the host. These mutations result in inactivation of the KatE stationary-phase catalase that protects high-density bacterial communities from oxidative stress and the BcsG cellulose biosynthetic enzyme required for the RDAR (red, dry, and rough) colonial phenotype. However, we found that like 14028s, D23580 is able to elicit an acute inflammatory response and cause enteritis in mice and rhesus macaque monkeys. Collectively, these observations suggest that African
S
. Typhimurium ST313 strain D23580 is becoming adapted to an anthroponotic mode of transmission while retaining the ability to infect and cause enteritis in multiple host species.

IMPORTANCE
The last 3 decades have witnessed an epidemic of invasive nontyphoidal
Salmonella
infections in sub-Saharan Africa. Genomic analysis and clinical observations suggest that the
Salmonella
strains responsible for these infections are evolving to become more typhoid-like with regard to patterns of transmission and virulence. This study shows that a prototypical African nontyphoidal
Salmonella
strain has lost traits required for environmental stress resistance, consistent with an adaptation to a human-to-human mode of transmission. However, in contrast to predictions, the strain remains capable of causing acute inflammation in the mammalian intestine. This suggests that the systemic clinical presentation of invasive nontyphoidal
Salmonella
infections in Africa reflects the immune status of infected hosts rather than intrinsic differences in the virulence of African
Salmonella
strains. Our study provides important new insights into the evolution of host adaptation in bacterial pathogens.
Sigmoid volvulus in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS): a rare occurrence
Authors: Hallac Alexander , Keshava Hari B , Morris-Stiff Gareth , Ibrahim Samuel
Published: March 2016

Mitochondrial diseases are rare and devastating, with a wide spectrum of clinical presentations and systemic symptoms. The majority of the published literature focuses on the neuromuscular manifestations and genetic components of this mitochondrial cytopathy, however, cardiac, renal, endocrine and gastrointestinal manifestations may also be present. The authors report a case detailing a 56-year-old woman's final hospitalisation from the gastrointestinal sequelae of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) (Co Q10 deficiency variant). She presented with abdominal pain and distension associated with lactic acidosis, and was shown on imaging to have a colon perforation. This resulted in emergent surgery at which a necrotic colon secondary to a sigmoid colon was identified. Following four subsequent operations, and the development of multiorgan failure, care was eventually withdrawn. Practitioners of patients with MELAS should be cognisant of the rare but devastating gastrointestinal consequences of mitochondrial diseases.
Cohort profile of the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register: current status and recent enhancement of an Electronic Mental Health Record-derived data resource
Authors: Perera Gayan , Broadbent Matthew , Callard Felicity , Chang Chin-Kuo , Downs Johnny , Dutta Rina , Fernandes Andrea , Hayes Richard D , Henderson Max , Jackson Richard , Jewell Amelia , Kadra Giouliana , Little Ryan , Pritchard Megan , Shetty Hitesh , Tulloch Alex , Stewart Robert
Published: March 2016

Purpose

The South London and Maudsley National Health Service (NHS) Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register and its Clinical Record Interactive Search (CRIS) application were developed in 2008, generating a research repository of real-time, anonymised, structured and open-text data derived from the electronic health record system used by SLaM, a large mental healthcare provider in southeast London. In this paper, we update this register's descriptive data, and describe the substantial expansion and extension of the data resource since its original development.

Participants

Descriptive data were generated from the SLaM BRC Case Register on 31 December 2014. Currently, there are over 250 000 patient records accessed through CRIS.

Findings to date

Since 2008, the most significant developments in the SLaM BRC Case Register have been the introduction of natural language processing to extract structured data from open-text fields, linkages to external sources of data, and the addition of a parallel relational database (Structured Query Language) output. Natural language processing applications to date have brought in new and hitherto inaccessible data on cognitive function, education, social care receipt, smoking, diagnostic statements and pharmacotherapy. In addition, through external data linkages, large volumes of supplementary information have been accessed on mortality, hospital attendances and cancer registrations.

Future plans

Coupled with robust data security and governance structures, electronic health records provide potentially transformative information on mental disorders and outcomes in routine clinical care. The SLaM BRC Case Register continues to grow as a database, with approximately 20 000 new cases added each year, in addition to extension of follow-up for existing cases. Data linkages and natural language processing present important opportunities to enhance this type of research resource further, achieving both volume and depth of data. However, research projects still need to be carefully tailored, so that they take into account the nature and quality of the source information.
Managing the screen-viewing behaviours of children aged 5–6 years: a qualitative analysis of parental strategies
Authors: Jago R , Zahra J , Edwards M J , Kesten J M , Solomon-Moore E , Thompson J L , Sebire S J
Published: March 2016

Objectives

The present study used qualitative methods to: (1) examine the strategies that were used by parents of children aged 5–6 years to manage screen viewing; (2) identify key factors that affect the implementation of the strategies and (3) develop suggestions for future intervention content.

Design

Telephone interviews were conducted with parents of children aged 5–6 years participating in a larger study. Interviews were transcribed verbatim and analysed using an inductive and deductive content analysis. Coding and theme generation was iterative and refined throughout.

Setting

Parents were recruited through 57 primary schools located in the greater Bristol area (UK).

Participants

53 parents of children aged 5–6 years.

Results

Parents reported that for many children, screen viewing was a highly desirable behaviour that was difficult to manage, and that parents used the provision of screen viewing as a tool for reward and/or punishment. Parents managed screen viewing by setting limits in relation to daily events such as meals, before and after school, and bedtime. Screen-viewing rules were often altered depending on parental preferences and tasks. Inconsistent messaging within and between parents represented a source of conflict at times. Potential strategies to facilitate reducing screen viewing were identified, including setting screen-viewing limits in relation to specific events, collaborative rule setting, monitoring that involves mothers, fathers and the child, developing a family-specific set of alternative activities to screen viewing and developing a child's ability to self-monitor their own screen viewing.

Conclusions

Managing screen viewing is a challenge for many parents and can often cause tension in the home. The data presented in this paper provide key suggestions of new approaches that could be incorporated into behaviour change programmes to reduce child screen viewing.
Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial—study protocol
Authors: Diem Ricarda , Molnar Fanni , Beisse Flemming , Gross Nikolai , Drüschler Katharina , Heinrich Sven P , Joachimsen Lutz , Rauer Sebastian , Pielen Amelie , Sühs Kurt-Wolfram , Linker Ralf Andreas , Huchzermeyer Cord , Albrecht Philipp , Hassenstein Andrea , Aktas Orhan , Guthoff Tanja , Tonagel Felix , Kernstock Christoph , Hartmann Kathrin , Kümpfel Tania , Hein Katharina , van Oterendorp Christian , Grotejohann Birgit , Ihorst Gabriele , Maurer Julia , Müller Matthias , Volkmann Martin , Wildemann Brigitte , Platten Michael , Wick Wolfgang , Heesen Christoph , Schiefer Ulrich , Wolf Sebastian , Lagrèze Wolf A
Published: March 2016

Introduction

Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function.

Methods and analysis

Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months.

Ethics and dissemination

TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP.

Trial registration number

NCT01962571.
Development of an implementation plan for the 6-PACK falls prevention programme as part of a randomised controlled trial: protocol for a series of preimplementation studies
Authors: Barker Anna L , Morello Renata T , Ayton Darshini R , Hill Keith D , Landgren Fiona S , Brand Caroline A
Published: March 2016

Background

Inhospital falls cause morbidity, staff burden and increased healthcare costs. It is unclear if the persistent problem of inhospital falls is due to the use of ineffective interventions or their suboptimal implementation. The 6-PACK programme appears to reduce fall injuries and a randomised controlled trial (RCT) was undertaken to confirm effects. This paper describes the protocol for the preimplementation studies that aimed to identify moderators of the effective use of the 6-PACK programme to inform the development of an implementation plan to be applied in the RCT.

Methods

The 6-PACK project included five preimplementation studies: (1) a profile of safety climate; (2) review of current falls prevention practice; (3) epidemiology of inhospital falls; (4) acceptability of the 6-PACK programme; and (5) barriers and enablers to implementation of the 6-PACK programme. The Theoretical Domain Framework that includes 12 behaviour change domains informed the design of these studies that involved 540 staff and 8877 patients from 24 wards from six Australian hospitals. Qualitative and quantitative methods were applied with data collected via: structured bedside observation; daily nurse unit manager verbal report of falls; audit of medical records, incident reporting and hospital administrative data; surveys of ward nurses; focus groups with ward nurses; and key informant interviews with senior staff.

Discussion

Information on contextual, system, intervention, patient and provider level factors is critical to the development of an implementation plan. Information gained from these studies was used to develop a plan applied in the RCT that addressed the barriers and harnessed enablers.

Trial registration number

The RCT is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000332921.
Implications of limiting mechanical thrombectomy to patients with emergent large vessel occlusion meeting top tier evidence criteria
Authors: Bhole Rohini , Goyal Nitin , Nearing Katherine , Belayev Andrey , Doss Vinodh T , Elijovich Lucas , Hoit Daniel A , Tsivgoulis Georgios , Alexandrov Andrei V , Arthur Adam S , Alexandrov Anne W
Published: March 2016

Background

Recent guidelines for endovascular management of emergent large vessel occlusion (ELVO) award top tier evidence to the same selective criteria in recent trials. We aimed to understand how guideline adherence would have impacted treatment numbers and outcomes in a cohort of patients from a comprehensive stroke center.

Methods

A retrospective observational study was conducted using consecutive emergent endovascular patients. Mechanical thrombectomy (MT) was performed with stent retrievers or large bore clot aspiration catheters. Procedural outcomes were compared between patients meeting, and those failing to meet, top tier evidence criteria.

Results

126 patients receiving MT from January 2012 to June 2015 were included (age 31–89 years, National Institutes of Health Stroke Scale (NIHSS) score 2–38); 62 (49%) patients would have been excluded if top tier criteria were upheld: pretreatment NIHSS score <6 (10%), Alberta Stroke Program Early CT score <6 (6.5%), premorbid modified Rankin Scale (mRS) score ≥2 (27%), M2 occlusion (10%), posterior circulation (32%), symptom to groin puncture >360 min (58%). 26 (42%) subjects had more than one top tier exclusion. Symptomatic intracerebral hemorrhage (sICH) and systemic hemorrhage rates were similar between the groups. 3 month mortality was 45% in those lacking top tier evidence compared with 26% (p=0.044), and 3 month mRS score 0–2 was 33% versus 46%, respectively (NS). After adjusting for potential confounders, top tier treatment was not associated with neurological improvement during hospitalization (β −8.2; 95% CI −24.6 to −8.2; p=0.321), 3 month mortality (OR=0.38; 95% CI 0.08 to 1.41), or 3 month favorable mRS (OR=0.97; 95% CI 0.28 to 3.35).

Conclusions

Our study showed that with strict adherence to top tier evidence criteria, half of patients may not be considered for MT. Our data indicate no increased risk of sICH and a potentially higher mortality that is largely due to treatment of patients with basilar occlusions and those treated at an extended time window. Despite this, good functional recovery is possible, and consideration of MT in patients not meeting top tier evidence criteria may be warranted.
Culture and spirituality: essential components of palliative care
Authors: Speck Peter
Published: March 2016

Palliative care advocates a holistic, multiprofessional approach to the care of people with life-threatening disease. In addition to the control of physical symptoms attention should also be paid to psychosocial, cultural and spiritual aspects of the patient's experience of illness. Guidance documents and research evidence reflect the complexity of the patient's journey and the need to regularly assess these areas of need over time. Cultural background can shape how patients respond to life-threatening illness, as can the beliefs held by the patients, whether religious or more broadly spiritual. Research evidence shows the importance of identifying and addressing cultural and spiritual aspects of care held by patients, families and staff. These are often neglected in clinical practice due to the focus on biomedical concerns and staff discomfort in engaging with beliefs and culture. Recent studies have highlighted gaps in the research, and some methodological difficulties and indicate many patients welcome healthcare staff enquiring about the importance of their beliefs and culture. Identifying research priorities is necessary to guide future research and strengthen the evidence base.
Nighttime feeding likely alters morning metabolism but not exercise performance in female athletes
Authors: Ormsbee Michael J. , Gorman Katherine A. , Miller Elizabeth A. , Baur Daniel A. , Eckel Lisa A. , Contreras Robert J. , Panton Lynn B. , Spicer Maria T.
Published: March 2016

The timing of morning endurance competition may limit proper pre-race fueling and resulting performance. A nighttime, pre-sleep nutritional strategy could be an alternative method to target the metabolic and hydrating needs of the early morning athlete without compromising sleep or gastrointestinal comfort during exercise. Therefore, the purpose of this investigation was to examine the acute effects of pre-sleep chocolate milk (CM) ingestion on next-morning running performance, metabolism, and hydration status. Twelve competitive female runners and triathletes (age, 30 ± 7 years; peak oxygen consumption, 53 ± 4 mL·kg−1·min−1) randomly ingested either pre-sleep CM or non-nutritive placebo (PL) ∼30 min before sleep and 7–9 h before a morning exercise trial. Resting metabolic rate (RMR) was assessed prior to exercise. The exercise trial included a warm-up, three 5-min incremental workloads at 55%, 65%, and 75% peak oxygen consumption, and a 10-km treadmill time trial (TT). Physiological responses were assessed prior, during (incremental and TT), and postexercise. Paired t tests and magnitude-based inferences were used to determine treatment differences. TT performances were not different (“most likely trivial” improvement with CM) between conditions (PL: 52.8 ± 8.4 min vs CM: 52.8 ± 8.0 min). RMR was “likely” increased (4.8%) and total carbohydrate oxidation (g·min−1) during exercise was “possibly” or likely increased (18.8%, 10.1%, 9.1% for stage 1–3, respectively) with CM versus PL. There were no consistent changes to hydration indices. In conclusion, pre-sleep CM may alter next-morning resting and exercise metabolism to favor carbohydrate oxidation, but effects did not translate to 10-km running performance improvements.
Evaluation of warm mix asphalt performance incorporating high RAP content
Authors: Lu Xuan Dai , Saleh Mofreh
Published: March 2016

Using reclaimed asphalt pavement (RAP) increases the sustainability benefits and can enhance the performance of warm mix asphalt (WMA) compared to traditional hot mix asphalt (HMA). However, the RAP content is generally limited in WMA because adding high RAP content may reduce the performance of WMA. In this paper, the authors studied the possibility of incorporating high RAP content from 25 to 70% by mass of WMA by using Evotherm as an additive. Laboratory performance of WMA–RAP mixtures was characterized and compared to a control HMA in terms of moisture susceptibility, rutting resistance, and fatigue characterization. Test results showed that Evotherm greatly improved the moisture resistance of WMA–RAP mixtures compared to HMA. Increasing RAP content made WMA–RAP mixtures stiffer and enhanced the rutting resistance, but decreased the fatigue resistance of the mixtures. Therefore, the maximum RAP content needs to be determined to ensure balance between the fatigue and rutting characteristics of asphalt mixtures.
Resident and cavity-nesting avian community is affected by amount but not age of white pine in central Ontario mature mixedwood forests
Authors: Thompson Ian D. , Wiebe Philip , Kirk David A.
Published: March 2016

Forests with old-growth white pines have been severely reduced compared with historical levels. We examined resident and cavity-nesting bird species abundances in winter and the breeding season, because some of these species may prefer old-forest habitats for breeding. We counted birds over 10 years in four mixedwood types: old pine, mature pine, mature nonpine, and selection-harvested stands. We expected that old pine stands would be selected by some species because of abundant snags and large trees for foraging. We assessed habitat use among years and changes following harvesting. Counts of nomadic species varied across years but counts for others did not. Species used old and mature pine mixedwoods equally and more than nonpine or harvested stands in winter and for breeding, but old stands were not preferred. Important variables included percent pine and large tree density. Selection harvesting benefitted Yellow-bellied Sapsuckers but reduced counts of Black-capped Chickadees and Brown Creepers. Black-capped Chickadees changed habitats between seasons and in some years. Black-backed Woodpeckers were most common in pine stands but abundant in harvested stands for 2 years following cutting. Regardless of stand age, large (>40 cm) pines provide important habitat for residents and cavity nesters.
Numerical investigation of three-dimensional hybrid Cu–Al2O3/water nanofluid flow over a stretching sheet with effecting Lorentz force subject to Newtonian heating
Authors: Devi S. Suriya Uma , Devi S.P. Anjali
Published: March 2016

This work compares the heat transfer characteristics of traditional nanofluid with that of emerging hybrid nanofluid. Hybrid nanofluid, a new type of conventional fluid, has been used toward the enhancement of heat transfer in the boundary layer flow. A new model of thermophysical properties is employed to investigate the effects of Lorentz force over a three-dimensional stretching surface subject to Newtonian heating. Comparisons are obtained through the numerical parametric study, which has been carried out to explore the effects of various physical parameters involved in the problem. From this study it is observed that the heat transfer rate of hybrid nanofluid (Cu–Al2O3/water) is higher than nanofluid (Cu/water) even in the presence of a magnetic field environment. By opting to use different and appropriate nanoparticle proportions in hybrid nanofluid, the desired heat transfer rate can be achieved.