bluuebunny/crossref_metadata_2025 huggingface dataset:
Modified Levenberg–Marquardt Algorithm for Backpropagation Neural Network Training in Dynamic Model Identification of Mechanical Systems
Authors: Li Ming , Wu Huapeng , Wang Yongbo , Handroos Heikki , Carbone Giuseppe
Published: October 2016

For modeling a dynamic system in practice, it often faces the difficulty in improving the accuracy of the constructed analytical model, since some components of the dynamic model are often ignored deliberately due to the difficulty of identification. It is also unwise to apply the neural network to approximate the entire dynamic system as a black box, when the comprehensive knowledge of most components of the dynamics of a large system are available. This paper proposes a method that utilizes the backpropagation (BP) neural network to identify the unknown components of the dynamic system based on the experimental front-end inputs–outputs data of the entire system. It can avoid the difficulty in getting the direct training data for the unknown components, and brings great benefits in the practical application, since to get the front-end inputs–outputs data of the entire dynamic system is easier and cost-effective. In order to train such neural network for the unknown components of dynamics, a modified Levenberg–Marquardt algorithm, which can utilize the front-end inputs–outputs data of the entire dynamic system, has been developed in the paper. Three examples from different application points of view are presented in the paper, and the results show that the proposed modified Levenberg–Marquardt algorithm is efficient to train the neural network for the unknown components of the system based on the data of entire system. The constructed dynamics model, in which the unknown components are substituted by the neural network, can satisfy the requisite accuracy successfully in the computation.
25+ Years of the Hubble Space Telescope and a Simple Error that Cost Millions
Authors: Shakerin Said
Published: October 2016

A simple mistake in properly setting up a measuring device caused millions of dollars to be spent in correcting the initial optical failure of the Hubble Space Telescope (HST). This short article is intended as a lesson for a physics laboratory and discussion of errors in measurement.
Measuring magnification of virtual images using digital cameras
Authors: Kutzner Mickey D. , Snelling Samantha
Published: October 2016

The concept of virtual images and why they lead to angular rather than linear magnification of optical images can be vague for students. A particularly straightforward method of obtaining quantitative magnification for simple magnifiers, microscopes, and telescopes uses the technology that students carry in their backpacks—their camera phones.
Which schools are included?
Authors: White Susan C.
Published: October 2016

We are continuing our examination of very different physics availability numbers reported by AIP Statistics and the U.S. Department of Education’s Office of Civil Rights (OCR). The essential difference appears to be the number of schools included in the denominator. The U.S. Department of Education classifies schools into one of five types based upon the curriculum offered: regular, special education, vocational, alternative, and a fifth classification for schools that do not fit into any of the first four. In AIP Statistics’ Quadrennial Survey of High School Physics Teachers, data are collected from a nationally representative sample of all public and private regular and vocational schools that have at least three seniors (students enrolled in 12th grade).
Robotic QM/MM-driven maturation of antibody combining sites
Authors: Smirnov Ivan V. , Golovin Andrey V. , Chatziefthimiou Spyros D. , Stepanova Anastasiya V. , Peng Yingjie , Zolotareva Olga I. , Belogurov Alexey A. , Kurkova Inna N. , Ponomarenko Natalie A. , Wilmanns Matthias , Blackburn G. Michael , Gabibov Alexander G. , Lerner Richard A.
Published: October 2016

Robotic QM/MM maturation in silico markedly improved targeted Ig reactivity.
‘Green hell’ has long been home for humans
Authors: Curry Andrew
Published: October 2016

By burning trees and tending crops, prehistoric people left a lasting mark on rainforests.
A photoreceptor's on-off switch
Authors: Fankhauser Christian , Ulm Roman
Published: October 2016

Light-induced protein interaction controls the signaling of a plant cryptochrome
Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia
Authors: Zhang Yange , Sakthivel Senthilkumar K. , Bramley Anna , Jain Seema , Haynes Amber , Chappell James D. , Hymas Weston , Lenny Noel , Patel Anami , Qi Chao , Ampofo Krow , Arnold Sandra R. , Self Wesley H. , Williams Derek J. , Hillyard David , Anderson Evan J. , Grijalva Carlos G. , Zhu Yuwei , Wunderink Richard G. , Edwards Kathryn M. , Pavia Andrew T. , McCullers Jonathan A. , Erdman Dean D.
Published: October 2016

Both molecular and serological assays have been used previously to determine the etiology of community-acquired pneumonia (CAP). However, the extent to which these methods are correlated and the added diagnostic value of serology for respiratory viruses other than influenza virus have not been fully evaluated. Using data from patients enrolled in the Centers for Disease Control and Prevention (CDC) Etiology of Pneumonia in the Community (EPIC) study, we compared real-time reverse transcription-PCR (RT-PCR) and serology for the diagnosis of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus 1 to 3 (PIV1, PIV2, and PIV3), and adenovirus (AdV) infections. Of 5,126 patients enrolled, RT-PCR and serology test results were available for 2,023, including 1,087 children below the age of 18 years and 936 adults. For RSV, 287 (14.2%) patients were positive by RT-PCR and 234 (11.6%) were positive by serology; for HMPV, 172 (8.5%) tested positive by RT-PCR and 147 (7.3%) by serology; for the PIVs, 94 (4.6%) tested positive by RT-PCR and 92 (4.6%) by serology; and for AdV, 111 (5.5%) tested positive by RT-PCR and 62 (3.1%) by serology. RT-PCR provided the highest number of positive detections overall, but serology increased diagnostic yield for RSV (by 11.8%), HMPV (by 25.0%), AdV (by 32.4%), and PIV (by 48.9%). The method concordance estimated by Cohen's kappa coefficient (κ) ranged from good (for RSV; κ = 0.73) to fair (for AdV; κ = 0.27). Heterotypic seroresponses observed between PIVs and persistent low-level AdV shedding may account for the higher method discordance observed with each of these viruses. Serology can be a helpful adjunct to RT-PCR for research-based assessment of the etiologic contribution of respiratory viruses other than influenza virus to CAP.
Performance of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Identifying Clinical Malassezia Isolates
Authors: Denis Julie , Machouart Marie , Morio Florent , Sabou Marcela , Kauffmann-LaCroix Catherine , Contet-Audonneau Nelly , Candolfi Ermanno , Letscher-Bru Valérie
Published: October 2016

The genus
Malassezia
comprises commensal yeasts on human skin. These yeasts are involved in superficial infections but are also isolated in deeper infections, such as fungemia, particularly in certain at-risk patients, such as neonates or patients with parenteral nutrition catheters. Very little is known about
Malassezia
epidemiology and virulence. This is due mainly to the difficulty of distinguishing species. Currently, species identification is based on morphological and biochemical characteristics. Only molecular biology techniques identify species with certainty, but they are time-consuming and expensive. The aim of this study was to develop and evaluate a matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) database for identifying
Malassezia
species by mass spectrometry. Eighty-five
Malassezia
isolates from patients in three French university hospitals were investigated. Each strain was identified by internal transcribed spacer sequencing. Forty-five strains of the six species
Malassezia
furfur
,
M. sympodialis
,
M. slooffiae
,
M. globosa
,
M. restricta
, and
M. pachydermatis
allowed the creation of a MALDI-TOF database. Forty other strains were used to test this database. All strains were identified by our
Malassezia
database with log scores of >2.0, according to the manufacturer's criteria. Repeatability and reproducibility tests showed a coefficient of variation of the log score values of <10%. In conclusion, our new
Malassezia
database allows easy, fast, and reliable identification of
Malassezia
species. Implementation of this database will contribute to a better, more rapid identification of
Malassezia
species and will be helpful in gaining a better understanding of their epidemiology.
Potent Inhibition of Human Cytomegalovirus by Modulation of Cellular SNARE Syntaxin 5
Authors: Cruz Linda , Streck Nicholas T. , Ferguson Kevin , Desai Trisha , Desai Dhimant H. , Amin Shantu G. , Buchkovich Nicholas J.
Published: October 2016

Formation of the cytoplasmic viral assembly compartment (cVAC) is an important step for efficient human cytomegalovirus (HCMV) assembly. To do this, the virus must alter and repurpose the normal cellular balance of membrane and protein flux, a process that is not well understood. Although a recent screen identified three viral proteins essential for cVAC formation, less is known about the contribution of cellular factors. We show that HCMV infection increases the protein level of a cellular trafficking factor, syntaxin 5 (STX5), a member of the syntaxin family of SNARE proteins. STX5 is recruited to the cVAC in infected cells and is required for the efficient production of infectious virions. We find that STX5 is important for normal cVAC morphology and the proper localization of viral proteins. A previously identified inhibitor of trafficking, Retro94, causes the mislocalization of STX5, an altered cVAC morphology, and dispersal of viral proteins. The presence of Retro94 results in severely impaired production of infectious virions, with a decrease as great as 5 logs. We show that this inhibition is conserved among different strains of HCMV and the various cell types that support infection, as well as for murine CMV. Thus, our data identify a key cellular trafficking factor important for supporting HCMV infection.

IMPORTANCE
Human cytomegalovirus (HCMV) infection causes severe disease and mortality in immunocompromised individuals, including organ transplant and AIDS patients. In addition, infection of a developing fetus may result in lifelong complications such as deafness and learning disabilities. Understanding in detail the processes involved in HCMV replication is important for developing novel treatments. One of these essential processes, assembly of infectious virions, takes places in the cytoplasmic viral assembly compartment. We identify a cellular protein, syntaxin 5, important for generating this compartment, and show that it is required for the efficient production of infectious virions. We also show that a small molecule that disrupts this protein also significantly reduces the amount of infectious virions that are generated. Thus, by pinpointing a cellular protein that is important in the replication cycle of HCMV, we identified a novel target that can be pursued for therapeutic intervention.
Host Cellular Protein TRAPPC6AΔ Interacts with Influenza A Virus M2 Protein and Regulates Viral Propagation by Modulating M2 Trafficking
Authors: Zhu Pengyang , Liang Libin , Shao Xinyuan , Luo Weiyu , Jiang Shuitao , Zhao Qingqing , Sun Nan , Zhao Yuhui , Li Junping , Wang Jinguang , Zhou Yuan , Zhang Jie , Wang Guangwen , Jiang Li , Chen Hualan , Li Chengjun
Published: October 2016

Influenza A virus (IAV) matrix protein 2 (M2) plays multiple roles in the early and late phases of viral infection. Once synthesized, M2 is translocated to the endoplasmic reticulum (ER), travels to the Golgi apparatus, and is sorted at the
trans
-Golgi network (TGN) for transport to the apical plasma membrane, where it functions in virus budding. We hypothesized that M2 trafficking along with its secretory pathway must be finely regulated, and host factors could be involved in this process. However, no studies examining the role of host factors in M2 posttranslational transport have been reported. Here, we used a yeast two-hybrid (Y2H) system to screen for host proteins that interact with the M2 protein and identified transport protein particle complex 6A (TRAPPC6A) as a potential binding partner. We found that both TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6A delta (TRAPPC6AΔ), interact with M2. Truncation and mutation analyses showed that the highly conserved leucine residue at position 96 of M2 is critical for mediating this interaction. The role of TRAPPC6AΔ in the viral life cycle was investigated by the knockdown of endogenous TRAPPC6AΔ with small interfering RNA (siRNA) and by generating a recombinant virus that was unable to interact with TRAPPC6A/TRAPPC6AΔ. The results indicated that TRAPPC6AΔ, through its interaction with M2, slows M2 trafficking to the apical plasma membrane, favors viral replication
in vitro
, and positively modulates virus virulence in mice.

IMPORTANCE
The influenza A virus M2 protein regulates the trafficking of not only other proteins but also itself along the secretory pathway. However, the host factors involved in the regulation of the posttranslational transport of M2 are largely unknown. In this study, we identified TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6AΔ, as interacting partners of M2. We found that the leucine (L) residue at position 96 of M2 is critical for mediating this interaction, which leads us to propose that the high level of conservation of 96L is a consequence of M2 adaptation to its interacting host factor TRAPPC6A/TRAPPC6AΔ. Importantly, we discovered that TRAPPC6AΔ can positively regulate viral replication
in vitro
by modulating M2 trafficking to the plasma membrane.
HIV-1 Tat Recruits HDM2 E3 Ligase To Target IRF-1 for Ubiquitination and Proteasomal Degradation
Authors: Remoli Anna Lisa , Marsili Giulia , Perrotti Edvige , Acchioni Chiara , Sgarbanti Marco , Borsetti Alessandra , Hiscott John , Battistini Angela
Published: October 2016

In addition to its ability to regulate HIV-1 promoter activation, the viral transactivator Tat also functions as a determinant of pathogenesis and disease progression by directly and indirectly modulating the host anti-HIV response, largely through the capacity of Tat to interact with and modulate the activities of multiple host proteins. We previously demonstrated that Tat modulated both viral and host transcriptional machinery by interacting with the cellular transcription factor interferon regulatory factor 1 (IRF-1). In the present study, we investigated the mechanistic basis and functional significance of Tat−IRF-1 interaction and demonstrate that Tat dramatically decreased IRF-1 protein stability. To accomplish this, Tat exploited the cellular HDM2 (human double minute 2 protein) ubiquitin ligase to accelerate IRF-1 proteasome-mediated degradation, resulting in a quenching of IRF-1 transcriptional activity during HIV-1 infection. These data identify IRF-1 as a new target of Tat-induced modulation of the cellular protein machinery and reveal a new strategy developed by HIV-1 to evade host immune responses.

IMPORTANCECurrent therapies have dramatically reduced morbidity and mortality associated with HIV infection and have converted infection from a fatal pathology to a chronic disease that is manageable via antiretroviral therapy. Nevertheless, HIV-1 infection remains a challenge, and the identification of useful cellular targets for therapeutic intervention remains a major goal. The cellular transcription factor IRF-1 impacts various physiological functions, including the immune response to viral infection. In this study, we have identified a unique mechanism by which HIV-1 evades IRF-1-mediated host immune responses and show that the viral protein Tat accelerates IRF-1 proteasome-mediated degradation and inactivates IRF-1 function. Restoration of IRF-1 functionality may thus be regarded as a potential strategy to reinstate both a direct antiviral response and a more broadly acting immune regulatory circuit.
Identification of Residues in the Lipopolysaccharide ABC Transporter That Coordinate ATPase Activity with Extractor Function
Authors: Simpson Brent W. , Owens Tristan W. , Orabella Matthew J. , Davis Rebecca M. , May Janine M. , Trauger Sunia A. , Kahne Daniel , Ruiz Natividad
Published: October 2016

The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, Gram-negative bacteria must extract newly synthesized LPS from the inner membrane, transport it across the aqueous periplasm, and translocate it across the outer membrane. The LptA to -G proteins assemble into a transenvelope complex that transports LPS from the inner membrane to the cell surface. The Lpt system powers LPS transport from the inner membrane by using a poorly characterized ATP-binding cassette system composed of the ATPase LptB and the transmembrane domains LptFG. Here, we characterize a cluster of residues in the groove region of LptB that is important for controlling LPS transport. We also provide the first functional characterization of LptFG and identify their coupling helices that interact with the LptB groove. Substitutions at conserved residues in these coupling helices compromise both the assembly and function of the LptB
2
FG complex. Defects in LPS transport conferred by alterations in the LptFG coupling helices can be rescued by changing a residue in LptB that is adjacent to functionally important residues in the groove region. This suppression is achieved by increasing the ATPase activity of the LptB
2
FG complex. Taken together, these data identify a specific binding site in LptB for the coupling helices of LptFG that is responsible for coupling of ATP hydrolysis by LptB with LptFG function to achieve LPS extraction.

IMPORTANCE
Lipopolysaccharide (LPS) is synthesized at the cytoplasmic membrane of Gram-negative bacteria and transported across several compartments to the cell surface, where it forms a barrier that protects these organisms from antibiotics. The LptB
2
FG proteins form an ATP-binding cassette (ABC) transporter that uses energy from ATP hydrolysis in the cytoplasm to facilitate extraction of LPS from the outer face of the cytoplasmic membrane prior to transport to the cell surface. How ATP hydrolysis is coupled with LPS release from the membrane is not understood. We have identified residues at the interface between the ATPase and the transmembrane domains of this heteromeric ABC complex that are important for LPS transport, some of which coordinate ATPase activity with LPS release.
Antifungal Drugs: The Current Armamentarium and Development of New Agents
Authors: Robbins Nicole , Wright Gerard D. , Cowen Leah E.
Published: October 2016

Invasive fungal infections are becoming an increasingly important cause of human mortality and morbidity, particularly for immunocompromised populations. The fungal pathogens
Candida albicans
,
Cryptococcus neoformans
, and
Aspergillus fumigatus
collectively contribute to over 1 million human deaths annually. Hence, the importance of safe and effective antifungal therapeutics for the practice of modern medicine has never been greater. Given that fungi are eukaryotes like their human host, the number of unique molecular targets that can be exploited for drug development remains limited. Only three classes of molecules are currently approved for the treatment of invasive mycoses. The efficacy of these agents is compromised by host toxicity, fungistatic activity, or the emergence of drug resistance in pathogen populations. Here we describe our current arsenal of antifungals and highlight current strategies that are being employed to improve the therapeutic safety and efficacy of these drugs. We discuss state-of-the-art approaches to discover novel chemical matter with antifungal activity and highlight some of the most promising new targets for antifungal drug development. We feature the benefits of combination therapy as a strategy to expand our current repertoire of antifungals and discuss the antifungal combinations that have shown the greatest potential for clinical development. Despite the paucity of new classes of antifungals that have come to market in recent years, it is clear that by leveraging innovative approaches to drug discovery and cultivating collaborations between academia and industry, there is great potential to bolster the antifungal armamentarium.
Host-Microsporidia Interactions in
Caenorhabditis elegans
, a Model Nematode Host
Authors: Troemel Emily R.
Published: October 2016

Microsporidia comprise a phylum of obligate intracellular pathogens related to fungi that infect virtually all animals. Recently, the nematode
Caenorhabditis elegans
has been developed as a convenient model for studying microsporidia infection in a whole-animal host through the identification and characterization of a natural microsporidian pathogen of this commonly studied laboratory organism. The
C. elegans
natural microsporidian pathogen is named
Nematocida parisii
, and it causes a lethal intestinal infection in
C. elegans
. Comparison of the genomes of
N. parisii
and its closely related species
Nematocida
sp. 1, together with the genomes of other microsporidian species, has provided insight into the evolutionary events that led to the emergence of the large, specialized microsporidia phylum. Cell biology studies of
N. parisii
infection in
C. elegans
have shown how
N. parisii
restructures host intestinal cells and, in particular, how it hijacks host exocytosis for nonlytic exit to facilitate transmission. Recent results also show how the host responds to infection with ubiquitin-mediated responses, and how a natural variant of
C. elegans
is able to clear
N. parisii
infection, but only during early life. Altogether, these studies provide insight into the mechanisms of microsporidia pathogenesis using a whole-animal host.
Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals
Authors: Weisman Ronit
Published: October 2016

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.
‘Omics’ biomarkers associated with chronic low back pain: protocol of a retrospective longitudinal study
Authors: Allegri Massimo , De Gregori Manuela , Minella Cristina E , Klersy Catherine , Wang Wei , Sim Moira , Gieger Christian , Manz Judith , Pemberton Iain K , MacDougall Jane , Williams Frances MK , Van Zundert Jan , Buyse Klaas , Lauc Gordan , Gudelj Ivan , Primorac Dragan , Skelin Andrea , Aulchenko Yurii S , Karssen Lennart C , Kapural Leonardo , Rauck Richard , Fanelli Guido
Published: October 2016

Introduction

Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the ‘-omics’ level (glycomics, Activomics and genome-wide association studies—GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP.

Methods and analysis

The study follows a two-phase, 1:2 case–control model. A total of 12 000 individuals (4000casesand 8000controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform -omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP.

Ethics and dissemination

The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals.

Trial registration number

NCT02037789; Pre-results.
Incidence and risk factors for capecitabine-induced symptomatic cardiotoxicity: a retrospective study of 452 consecutive patients with metastatic breast cancer
Authors: Polk Anne , Shahmarvand Nahid , Vistisen Kirsten , Vaage-Nilsen Merete , Larsen Finn Ole , Schou Morten , Nielsen Dorte Lisbeth
Published: October 2016

Objectives

Case reports of capecitabine cardiotoxicity resemble those seen with intravenous 5-fluorouracil (5-FU) with chest pain as the predominant manifestation, but few studies of capecitabine cardiotoxicity are available. We aimed to determine the incidence of symptomatic cardiotoxicity from capecitabine in patients with breast cancer and to identify risk factors.

Methods

We reviewed medical records of consecutive women with breast cancer treated with capecitabine (1000 mg/m2two times per day) from 2002 to 2012 at one institution.

Results

22 of 452 patients (4.9%) (95% CI 2.9% to 6.9%) had symptoms of cardiotoxicity (chest pain: n=13, dyspnoea: n=9, palpitations: n=2). 11 patients had changes on ECG (atrial fibrillation: n=5, ST deviations: n=3, T-wave abnormalities: n=2 and QTc prolongation: n=1). 2 patients (0.4%) sustained acute myocardial infarction. 1 patient (0.2%) developed cardiac arrest with lethal outcome. 4 of 6 patients (66%) retreated with capecitabine had recurrent symptoms at retreatment. Cardiac comorbidity (p=0.001), hypercholesterolaemia (p=0.005) and current smoking (p=0.023) were risk factors for cardiotoxicity in univariate analyses and remained significant when adjusted for age. Patients with cardiac comorbidity were 5.5 times (95% CI 2.0 to 14.8) more likely to develop cardiotoxicity. In the subgroup of patients with apparently no cardiac comorbidity, the incidence of cardiotoxicity was lower (3.7%) and hypercholesterolaemia (p=0.035) and current smoking (p=0.020) were risk factors of cardiotoxicity.

Conclusions

The incidence of cardiotoxicity from capecitabine resembles that of intravenous 5-FU (≈5%). Cardiac comorbidity, hypercholesterolaemia and current smoking were associated with development of cardiotoxicity.
Parenting acceptance and commitment therapy: a randomised controlled trial of an innovative online course for families of children with cerebral palsy
Authors: Whittingham Koa , Sheffield Jeanie , Boyd Roslyn N
Published: October 2016

Introduction

Cerebral palsy (CP) impacts on the entire family in a manner that is long-term, complex and multifactorial. In addition, the quality of the parent–child relationship impacts on many and varied child outcomes, making the provision of easily accessible and evidence-based support to parents of children with CP a priority. This paper reports the protocol of a randomised controlled trial of an innovative and translatable online intervention, parenting acceptance and commitment therapy (PACT), for families of children with CP. We predict that participating in the PACT programme will be associated with improvements in the parent–child relationship, in child functioning and in adjustment and quality of life for both parent and child.

Methods and analysis

We aim to recruit 66 parents of children (2–10 years old) diagnosed with CP to this study. Families will be randomly assigned to two groups: wait-list control and PACT. PACT is a parenting intervention grounded in acceptance and commitment therapy (ACT) and developed into an online course ‘PARENT101 Parenting with Purpose’ using the edX platform. All participants will be offered PACT before completion of the study. Assessments will take place at baseline, following completion of PACT and at 6-month follow-up (retention) and will focus on the parent–child relationship, parent and child adjustment and parent and child quality of life. Analysis will follow standard methods for randomised controlled trials using general linear models, specifically analysis of variance or analysis of covariance.

Ethics and dissemination

Ethics approvals have been obtained through the Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/15/QRCH/115) and The University of Queensland (2015001743). If efficacy is demonstrated, then the PARENT101 course has the potential to be disseminated widely in an accessible manner and at minimal cost. Further, the PACT framework may provide a blueprint for similar online courses with parents in a full range of contexts.

Trial registration number

ACTRN12616000351415; Pre-results.
Abstracts from international Emergency Medicine journals
Authors: Weber Ellen J
Published: October 2016

Editor's note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors.
An outcomes-based grading scale for the evaluation of cerebral aneurysms treated with flow diversion
Authors: Park Min S , Mazur Marcus D , Moon Karam , Nanaszko Michael J , Kestle John R W , Shah Lubdha M , Winegar Blair , Albuquerque Felipe C , Taussky Philipp , McDougall Cameron G
Published: October 2016

Object

Despite the popularity of flow-diverting stents for the treatment of cerebral aneurysms, there is no widely accepted scale for the characterization of results. We present an outcomes-based grading scale that considers factors related to failure of flow diversion.

Methods

The grading scale was developed using the results from consecutive patients at two institutions who were treated with flow diversion for a cerebral aneurysm. The initial treatment results were graded on patient, aneurysm, and treatment characteristics. A 6-point grading scale was developed based on these data.

Results

One hundred and seventy-one patients were included in the patient cohort. When compared by multivariate analysis with patients without residuals, patients with aneurysm residuals were found to be older (age ≥60 years, p=0.01, OR 1.17, 95% CI 1.03 to 1.33), to have larger aneurysms (size ≥15 mm, p<0.01, OR 1.38, 95% CI 1.17 to 1.62), to have aneurysms with associated side branches (p=0.02, OR 1.17, 95% CI 1.03 to 1.33), and to have a post-treatment Raymond score of 2 or 3 (p=0.01, OR 1.28, 95% CI 1.06 to 1.56). Using the Raymond score (1–3) as the foundation for the grading scale, additional points (0 or 1) were given for the other three identified factors, creating a 6-point scale. We found that patients with residual aneurysms had statistically higher final tabulated scores (p<0.01).

Conclusions

We propose a novel straightforward outcomes-based scale to characterize results after flow diversion treatment of cerebral aneurysms. This scale may provide the basis for the common reporting of results in future studies.
Silver-catalyzed carbon–selenium cross-coupling usingN-(phenylseleno)phthalimide: an alternate approach to the synthesis of organoselenides
Authors: Mukherjee Nirmalya , Pal Subhajit , Saha Amit , Ranu Brindaban C.
Published: October 2016

Silver(I) catalyzed phenylselenylation of terminal alkynes and organoboronic acids has been demonstrated using N-(phenylseleno)phthalimide as an electrophilic SePh donor. A wide variety of terminal alkynes and organoboronic acids are selenylated efficiently to produce the corresponding alkynyl and diaryl selenides, respectively, in good yields. Silver(I) acts as a Lewis acid in this process.
Discussion of “Glacier velocities and dynamic discharge from the ice masses of Baffin Island and Bylot Island, Nunavut, Canada”
Authors: Ommanney C. Simon L.
Published: October 2016

A similar investigation into calving glaciers and iceberg production on Baffin and Bylot islands was initiated by the Canadian Government in the 1970s. This is described and reference made to the Glacier Atlas of Canada, which, in identifying all individual glaciers in this region of the Canadian Arctic, obviates the need to develop an independent numbering system when individual glaciers need to be identified.
Electron–electron two-stream instability in embedded assembly of nanoparticle (NP) cluster in n-GaAs
Authors: Ghosh S. , Dubey Priya
Published: October 2016

The electron–electron two-stream instability has been studied in two-valley n-GaAs embedded with nanoparticle (NP) cluster. We considered polar optical phonon as the dominant intravalley scattering mechanism and drifted Maxwellian to approximate the distribution of carriers between each valley. We derived the dispersion relation for electrostatic wave using hydrodynamic model of plasmas. While investigating temporal behaviour, we found two novel modes of propagation. These two novel modes are found to be evanescent by nature and propagate with equal phase velocities, but in opposite directions. The pre-existing modes retained their profile structures even in the presence of NP cluster. On the other hand, in the case of convective instability, no new modes are obtained but the propagation and gain profiles of the preexisting modes are significantly modified by the presence of NP cluster in the host medium.
Numerical simulation of heat transfer in a micro-cavity
Authors: Baliti J. , Hssikou M. , Alaoui M.
Published: October 2016

The behaviour of rarefied monatomic gas of Maxwell particles within a rectangular enclosure is investigated, with the Navier–Stokes and Fourier field of equations with first- (NSF) and second-order boundary conditions (NSF2) of the velocity slip and temperature jump, and the regularized 13 moments approach (R13). The enclosure considered has a heated bottom with lateral walls that have specular reflection. The effect of the three dimensionless parameters characterizing the simulated problem, the cavity aspect ratio, the Knudsen number, and the temperature ratio of the hot over the cold walls, on the flow and bulk quantities is examined. For the small Knudsen numbers the flow presents one type of streamlines from the cold to hot plate in both NSF and R13 theories, while by increasing the Knudsen number the flow becomes more complex and presents hot to cold flow streamlines in the extended approach of R13. These rarefaction effects cannot be predicted by the classical continuum approach of NSF. The increase of the temperature ratio in R13 affects the hot to cold flow, which begins to vanish, while this type of streamline does not appear by decreasing the aspect ratio.
Vortex shedding control on a bare cylinder using hexagonal perforated outer cylinder
Authors: Akar Mustafa Atakan , Kucuk Mehmet
Published: October 2016

The aim of the study is to observe the effect of outer hexagonal perforated cylinder surrounding an inner cylinder on vortex structure behind bluff body. Vortex shedding characteristics from bluff body are experimentally studied by particle image velocimetry (PIV) in deep water. The inner cylinder had seven different diameters (Di), varied from 30 to 90 mm with an increment of 10 mm and the hexagonally perforated outer cylinder placed outside of the inner cylinder was used as a control element. Experiments were carried out with six perforated cylinders with a diameters of 100 mm (Do) and six porosities, β, with hole diameter 10 mm. The porosity, β, and diameter ratio, Di/Do, had substantial effect on the flow characteristics behind the cylinder. For the range of diameter ratios of 0.3 ≤ Di/Do ≤ 0.5 the optimum porosity that controls the flow structure is found to be β = 0.6. For 0.6 ≤ Di/Do ≤ 0.7 it is β = 0.5 and β = 0.4 for 0.8 ≤ Di/Do ≤ 0.9. With increasing diameter ratio, Di/Do, peak magnitude locations of Reynolds shear stress, [Formula: see text], and turbulence kinetic energy approach the inner outer cylinder system slightly. For all diameter ratios, β = 0.6 is the most effective porosity ratio.
Pointwise Error Estimation for the One-Dimensional Transport Equation Based on the Variational Multiscale Method
Authors: Irisarri Diego , Hauke Guillermo
Published: October 2016

This paper presents an exact pointwise error estimator applied to the transport equation. The error estimate, which is represented by a combination of residual-free bubble and Green’s functions, is computed by postprocessing the finite element solution. The fine or unresolved scales are analyzed applying the variational multiscale method. The technology can be applied to linear and high-order elements. Numerical examples are presented in which the satisfactory results corroborate the theoretical foundations.
Environmental Issues in Central Africa
Authors: Abernethy Katharine , Maisels Fiona , White Lee J.T.
Published: October 2016

The Central African forests, the planet's second largest rainforest block, are key to global environmental health. They influence climate change through their crucial role in carbon sinking and storage, affect weather patterns across Africa, and safeguard unique species and biodiverse communities. Their fate is important to everyone, not just today's inhabitants. The forests cover seven countries, and the differing socioeconomic histories and trajectories of these nations determine divergent fates for people, trees, and wildlife across the region. We review current knowledge of how the Central African forests have been shaped by climate and human activity within the region and assess how they may evolve under future climate change, population growth, and the Anthropocene race for wealth and energy. We highlight three different environmental trajectories for the countries of the region, identify key current regional issues that have an international dimension, and highlight five new points of future concern.
Capabilities and Limitations of Peripheral Vision
Authors: Rosenholtz Ruth
Published: October 2016

This review discusses several pervasive myths about peripheral vision, as well as what is actually true: Peripheral vision underlies a broad range of visual tasks, in spite of its significant loss of information. New understanding of peripheral vision, including likely mechanisms, has deep implications for our understanding of vision. From peripheral recognition to visual search, from change blindness to getting the gist of a scene, a lossy but relatively fixed peripheral encoding may determine the difficulty of many tasks. This finding suggests that the visual system may be more stable, and less dynamically changing as a function of attention, than previously assumed.
Evolution of Concepts and Technologies in Ophthalmic Laser Therapy
Authors: Palanker Daniel
Published: October 2016

Ophthalmology was the first medical specialty to adopt lasers right after their invention more than 50 years ago, and they gradually revolutionized ocular imaging, diagnostics, therapy, and surgery. Challenging precision, safety, and selectivity requirements for ocular therapeutic and surgical procedures keep advancing the laser technologies, which in turn continue enabling novel applications for the preservation and restoration of sight. Modern lasers can provide single-cell-layer selectivity in therapy, submicrometer precision in three-dimensional image-guided surgery, and nondamaging retinal therapy under optoacoustic temperature control. This article reviews the evolution of laser technologies; progress in understanding of the laser–tissue interactions; and concepts, misconceptions, and accidental discoveries that led to modern therapeutic and surgical applications of lasers in ophthalmology. It begins with a brief historical overview, followed by a description of the laser–tissue interactions and corresponding ophthalmic applications.
Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61
Authors: Hao Feng , Zhang Fuqiang , Wu Daniel Dongwei , An Dong , Shi Jing , Li Guohong , Xu Xuemin , Cui Mei-Zhen
Published: October 2016

Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low-density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly induced CCN1 expression (approximately six- to sevenfold) in neointimal lesions. Downregulation of CCN1 expression with the specific CCN1 siRNA in carotid arteries blocked LPA-induced neointimal formation, indicating that CCN1 is essential in LPA-induced neointimal formation. We then used LPA receptor knockout (LPA1−/−, LPA2−/−, and LPA3−/−) mice to examine LPA receptor function in CCN1 expression in vivo and in LPA-induced neointimal formation. Our data reveal that LPA1 deficiency, but not LPA2 or LPA3 deficiency, prevents LPA-induced CCN1 expression in vivo in mouse carotid arteries. We also observed that LPA1 deficiency blunted LPA infusion-induced neointimal formation, indicating that LPA1 is the major mediator for LPA-induced vascular remodeling. Our in vivo model of LPA-induced neointimal formation established a key role of the ECM protein CCN1 in mediating LPA-induced neointimal formation. Our data support the notion that the LPA1-CCN1 axis may be the central control for SMC migration and vascular remodeling. CCN1 may serve as an important vascular disease marker and potential target for vascular therapeutic intervention.
Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels
Authors: Matthewman Cristina , Miller-Fleming Tyne W. , Miller David M. , Bianchi Laura
Published: October 2016

Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na+ and Ca2+, raising the possibility that direct Ca2+ influx through these channels contributes to intracellular Ca2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca2+ permeable, yet it is neurotoxic, suggesting that Na+ influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca2+ block in the Xenopus oocyte expression system. Thus, MEC-4(d) and UNC-8(d) differ both in current amplitude and Ca2+ permeability. Given that these two channels show a striking difference in toxicity, we wondered how Na+ conductance vs. Ca2+ permeability contributes to cell death. To address this question, we built an UNC-8/MEC-4 chimeric channel that retains the calcium permeability of MEC-4 and characterized its properties in Xenopus oocytes. Our data support the hypothesis that for Ca2+-permeable DEG/ENaC channels, both Ca2+ permeability and Na+ conductance contribute to toxicity. However, for Ca2+-impermeable DEG/ENaCs (e.g., UNC-8), our evidence shows that constitutive Na+ conductance is sufficient to induce toxicity, and that this effect is enhanced as current amplitude increases. Our work further refines the contribution of different channel properties to cellular toxicity induced by hyperactive DEG/ENaC channels.
Advanced spatiotemporal mapping methods give new insights into the coordination of contractile activity in the stomach of the rat
Authors: Lentle R. G. , Reynolds G. W. , Hulls C. M. , Chambers J. P.
Published: October 2016

We used spatiotemporal mapping of strain rate to determine the direction of propagation and amplitudes of the longitudinal and circumferential components of antrocorporal (AC) contractions and fundal contractions in the rat stomach maintained ex vivo and containing a volume of fluid that was within its normal functional capacity. In the region of the greater curvature the longitudinal and circular components of AC contractions propagated synchronously at right angles to the arciform geometric axis of the stomach. However, the configuration of AC contractions was U shaped, neither the circular nor the longitudinal component of contractions being evident in the upper proximal corpus. Similarly, in the distal upper antrum of some preparations, circumferential components propagated more rapidly than longitudinal components. Ongoing “high-frequency, low-amplitude myogenic contractions” were identified in the upper proximal gastric corpus and on the anterior and posterior wall of the fundus. The amplitudes of these contractions were modulated in the occluded stomach by low-frequency pressure waves that occurred spontaneously. Hence the characteristics of phasic contractions vary regionally in the antrum and corpus and a previously undescribed high-frequency contractile component was identified in the proximal corpus and fundus, the latter being modulated in synchrony with cyclic variation in intrafundal pressure in the occluded fundus.