bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013
Authors: Nelson Martha I. , Stucker Karla M. , Schobel Seth A. , Trovão Nídia S. , Das Suman R. , Dugan Vivien G. , Nelson Sarah W. , Sreevatsan Srinand , Killian Mary L. , Nolting Jacqueline M. , Wentworth David E. , Bowman Andrew S.
Published: September 2016

The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio (
n
= 262) and Indiana (
n
= 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans.

IMPORTANCE
Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.
Immune- and Nonimmune-Compartment-Specific Interferon Responses Are Critical Determinants of Herpes Simplex Virus-Induced Generalized Infections and Acute Liver Failure
Authors: Parker Zachary M. , Pasieka Tracy Jo , Parker George A. , Leib David A.
Published: September 2016

The interferon (IFN) response to viral pathogens is critical for host survival. In humans and mouse models, defects in IFN responses can result in lethal herpes simplex virus 1 (HSV-1) infections, usually from encephalitis. Although rare, HSV-1 can also cause fulminant hepatic failure, which is often fatal. Although herpes simplex encephalitis has been extensively studied, HSV-1 generalized infections and subsequent acute liver failure are less well understood. We previously demonstrated that IFN-αβγR
−/−
mice are exquisitely susceptible to liver infection following corneal infection with HSV-1. In this study, we used bone marrow chimeras of IFN-αβγR
−/−
(AG129) and wild-type (WT; 129SvEv) mice to probe the underlying IFN-dependent mechanisms that control HSV-1 pathogenesis. After infection, WT mice with either IFN-αβγR
−/−
or WT marrow exhibited comparable survival, while IFN-αβγR
−/−
mice with WT marrow had a significant survival advantage over their counterparts with IFN-αβγR
−/−
marrow. Furthermore, using bioluminescent imaging to maximize data acquisition, we showed that the transfer of IFN-competent hematopoietic cells controlled HSV-1 replication and damage in the livers of IFN-αβγR
−/−
mice. Consistent with this, the inability of IFN-αβγR
−/−
immune cells to control liver infection in IFN-αβγR
−/−
mice manifested as profoundly elevated aspartate transaminase (AST) and alanine transaminase (ALT) levels, indicative of severe liver damage. In contrast, IFN-αβγR
−/−
mice receiving WT marrow exhibited only modest elevations of AST and ALT levels. These studies indicate that IFN responsiveness of the immune system is a major determinant of viral tropism and damage during visceral HSV infections.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) infection is an incurable viral infection with the most significant morbidity and mortality occurring in neonates and patients with compromised immune systems. Severe pathologies from HSV include the blindness-inducing herpetic stromal keratitis, highly debilitating and lethal herpes simplex encephalitis, and generalized infections that can lead to herpes simplex virus-induced acute liver failure. While immune compromise is a known factor, the precise mechanisms that lead to generalized HSV infections are unknown. In this study, we used and developed a mouse model system in combination with real-time bioluminescence imaging to demonstrate the relative importance of the immune and nonimmune compartments for containing viral spread and promoting host survival after corneal infection. Our results shed light on the pathogenesis of HSV infections that lead to generalized infection and acute liver failure.
TRIM5α Resistance Escape Mutations in the Capsid Are Transferable between Simian Immunodeficiency Virus Strains
Authors: Wu Fan , Kirmaier Andrea , White Ellen , Ourmanov Ilnour , Whitted Sonya , Matsuda Kenta , Riddick Nadeene , Hall Laura R. , Morgan Jennifer S. , Plishka Ronald J. , Buckler-White Alicia , Johnson Welkin E. , Hirsch Vanessa M.
Published: September 2016

TRIM5α polymorphism limits and complicates the use of simian immunodeficiency virus (SIV) for evaluation of human immunodeficiency virus (HIV) vaccine strategies in rhesus macaques. We previously reported that the TRIM5α-sensitive SIV from sooty mangabeys (SIVsm) clone SIVsmE543-3 acquired amino acid substitutions in the capsid that overcame TRIM5α restriction when it was passaged in rhesus macaques expressing restrictive TRIM5α alleles. Here we generated TRIM5α-resistant clones of the related SIVsmE660 strain without animal passage by introducing the same amino acid capsid substitutions. We evaluated one of the variants in rhesus macaques expressing permissive and restrictive TRIM5α alleles. The SIVsmE660 variant infected and replicated in macaques with restrictive TRIM5α genotypes as efficiently as in macaques with permissive TRIM5α genotypes. These results demonstrated that mutations in the SIV capsid can confer SIV resistance to TRIM5α restriction without animal passage, suggesting an applicable method to generate more diverse SIV strains for HIV vaccine studies.

IMPORTANCE
Many strains of SIV from sooty mangabey monkeys are susceptible to resistance by common rhesus macaque TRIM5α alleles and result in reduced virus acquisition and replication in macaques that express these restrictive alleles. We previously observed that spontaneous variations in the capsid gene were associated with improved replication in macaques, and the introduction of two amino acid changes in the capsid transfers this improved replication to the parent clone. In the present study, we introduced these mutations into a related but distinct strain of SIV that is commonly used for challenge studies for vaccine trials. These mutations also improved the replication of this strain in macaques with the restrictive TRIM5α genotype and thus will eliminate the confounding effects of TRIM5α in vaccine studies.
Bipartite Network Analysis of the Archaeal Virosphere: Evolutionary Connections between Viruses and Capsidless Mobile Elements
Authors: Iranzo Jaime , Koonin Eugene V. , Prangishvili David , Krupovic Mart
Published: September 2016

Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order
Caudovirales
and the families
Turriviridae
and
Sphaerolipoviridae
that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere.

IMPORTANCE
Viruses infecting archaea are among the most mysterious denizens of the virosphere. Many of these viruses display no genetic or even morphological relationship to viruses of bacteria and eukaryotes, raising questions regarding their origins and position in the global virosphere. Analysis of 5,740 protein sequences from 116 genomes allowed dissection of the archaeal virus network and showed that most groups of archaeal viruses are evolutionarily connected to capsidless mobile genetic elements, including various plasmids and transposons. This finding could reflect actual independent origins of the distinct groups of archaeal viruses from different nonviral elements, providing important insights into the emergence and evolution of the archaeal virome.
Single-Nucleotide Resolution Mapping of Hepatitis B Virus Promoters in Infected Human Livers and Hepatocellular Carcinoma
Authors: Altinel Kübra , Hashimoto Kosuke , Wei Yu , Neuveut Christine , Gupta Ishita , Suzuki Ana Maria , Dos Santos Alexandre , Moreau Pierrick , Xia Tian , Kojima Soichi , Kato Sachi , Takikawa Yasuhiro , Hidaka Isao , Shimizu Masahito , Matsuura Tomokazu , Tsubota Akihito , Ikeda Hitoshi , Nagoshi Sumiko , Suzuki Harukazu , Michel Marie-Louise , Samuel Didier , Buendia Marie Annick , Faivre Jamila , Carninci Piero
Published: September 2016

Hepatitis B virus (HBV) is a major cause of liver diseases, including hepatocellular carcinoma (HCC), and more than 650,000 people die annually due to HBV-associated liver failure. Extensive studies of individual promoters have revealed that heterogeneous RNA 5′ ends contribute to the complexity of HBV transcriptome and proteome. Here, we provide a comprehensive map of HBV transcription start sites (TSSs) in human liver, HCC, and blood, as well as several experimental replication systems, at a single-nucleotide resolution. Using CAGE (cap analysis of gene expression) analysis of 16 HCC/nontumor liver pairs, we identify 17 robust TSSs, including a novel promoter for the X gene located in the middle of the gene body, which potentially produces a shorter X protein translated from the conserved second start codon, and two minor antisense transcripts that might represent viral noncoding RNAs. Interestingly, transcription profiles were similar in HCC and nontumor livers, although quantitative analysis revealed highly variable patterns of TSS usage among clinical samples, reflecting precise regulation of HBV transcription initiation at each promoter. Unlike the variety of TSSs found in liver and HCC, the vast majority of transcripts detected in HBV-positive blood samples are pregenomic RNA, most likely generated and released from liver. Our quantitative TSS mapping using the CAGE technology will allow better understanding of HBV transcriptional responses in further studies aimed at eradicating HBV in chronic carriers.

IMPORTANCE
Despite the availability of a safe and effective vaccine, HBV infection remains a global health problem, and current antiviral protocols are not able to eliminate the virus in chronic carriers. Previous studies of the regulation of HBV transcription have described four major promoters and two enhancers, but little is known about their activity in human livers and HCC. We deeply sequenced the HBV RNA 5′ ends in clinical human samples and experimental models by using a new, sensitive and quantitative method termed cap analysis of gene expression (CAGE). Our data provide the first comprehensive map of global TSS distribution over the entire HBV genome in the human liver, validating already known promoters and identifying novel locations. Better knowledge of HBV transcriptional activity in the clinical setting has critical implications in the evaluation of therapeutic approaches that target HBV replication.
Pathogenesis and Transmission Assessments of Two H7N8 Influenza A Viruses Recently Isolated from Turkey Farms in Indiana Using Mouse and Ferret Models
Authors: Sun Xiangjie , Belser Jessica A. , Pulit-Penaloza Joanna A. , Zeng Hui , Lewis Amanda , Shieh Wun-Ju , Tumpey Terrence M. , Maines Taronna R.
Published: September 2016

Avian influenza A H7 viruses have caused multiple outbreaks in domestic poultry throughout North America, resulting in occasional infections of humans in close contact with affected birds. In early 2016, the presence of H7N8 highly pathogenic avian influenza (HPAI) viruses and closely related H7N8 low-pathogenic avian influenza (LPAI) viruses was confirmed in commercial turkey farms in Indiana. These H7N8 viruses represent the first isolation of this subtype in domestic poultry in North America, and their virulence in mammalian hosts and the potential risk for human infection are largely unknown. In this study, we assessed the ability of H7N8 HPAI and LPAI viruses to replicate
in vitro
in human airway cells and
in vivo
in mouse and ferret models. Both H7N8 viruses replicated efficiently
in vitro
and
in vivo
, but they exhibited substantial differences in disease severity in mammals. In mice, while the H7N8 LPAI virus largely remained avirulent, the H7N8 HPAI virus exhibited greater infectivity, virulence, and lethality. Both H7N8 viruses replicated similarly in ferrets, but only the H7N8 HPAI virus caused moderate weight loss, lethargy, and mortality. The H7N8 LPAI virus displayed limited transmissibility in ferrets placed in direct contact with an inoculated animal, while no transmission of H7N8 HPAI virus was detected. Our results indicate that the H7N8 avian influenza viruses from Indiana are able to replicate in mammals and cause severe disease but with limited transmission. The recent appearance of H7N8 viruses in domestic poultry highlights the need for continued influenza surveillance in wild birds and close monitoring of the potential risk to human health.

IMPORTANCE
H7 influenza viruses circulate in wild birds in the United States, but when the virus emerges in domestic poultry populations, the frequency of human exposure and the potential for human infections increases. An H7N8 highly pathogenic avian influenza (HPAI) virus and an H7N8 low-pathogenic avian influenza (LPAI) virus were recently isolated from commercial turkey farms in Indiana. To determine the risk that these influenza viruses pose to humans, we assessed their pathogenesis and transmission
in vitro
and in mammalian models. We found that the H7N8 HPAI virus exhibited enhanced virulence, and although transmission was only observed with the H7N8 LPAI virus, the ability of this H7 virus to transmit in a mammalian host and quickly evolve to a more virulent strain is cause for concern. Our findings offer important insight into the potential for emerging H7 avian influenza viruses to acquire the ability to cause disease and transmit among mammals.
Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells
Authors: Lacombe Benoît , Morel Marina , Margottin-Goguet Florence , Ramirez Bertha Cecilia
Published: September 2016

Tat protein, the HIV transactivator, regulates transcription of the HIV genome by the host transcription machinery. Efficient inhibitors of HIV transcription that target Tat or the cellular cofactor NF-κB are well known. However, inhibition of HIV Tat-dependent transcription by targeting the general transcription and DNA repair factor II human (TFIIH) has not been reported. Here, we show that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4
+
T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat-dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection. Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy.

IMPORTANCE
Transcription from the HIV promoter is regulated by the combined activities of the host transcription machinery and the viral transactivator Tat protein. Here, we report that the drug spironolactone—an antagonist of aldosterone—blocks viral Tat-dependent transcription, thereby inhibiting both HIV-1 and HIV-2 infection of permissive T cells. This inhibition relies on the degradation of the cellular helicase XPB, a component of the TFIIH transcription factor complex. Consequently, XPB appears to be a novel HIV cofactor. Our discovery of the HIV-inhibitory activity of spironolactone opens the way for the development of novel anti-HIV strategies targeting a cellular cofactor without the limitations of antiretroviral therapy of drug resistance and high cost.
How many children and young people with life-limiting conditions are clinically unstable? A national data linkage study
Authors: Jarvis Stuart , Parslow Roger C , Carragher Pat , Beresford Bryony , Fraser Lorna K
Published: September 2016

Objective

To determine the clinical stage (stable, unstable, deteriorating or dying) for children and young people (CYP) aged 0–25 years in Scotland with life-limiting conditions (LLCs).

Design

National cohort of CYP with LLCs using linked routinely collected healthcare data.

Setting

Scotland.

Patients

20 436 CYP identified as having LLCs and resident in Scotland between 1 April 2009 and 31 March 2014.

Main outcome

Clinical stage based on emergency inpatient and intensive care unit admissions and date of death.

Results

Over 2200 CYP with LLCs in Scotland were unstable, deteriorating or dying in each year. Compared with 1-year-olds to 5-year-olds, children under 1 year of age had the highest risk of instability (OR 6.4, 95% CI 5.7 to 7.1); all older age groups had lower risk. Girls were more likely to be unstable than boys (OR 1.15, 95% CI 1.06 to 1.24). CYP of South Asian (OR 1.61, 95% CI 1.28 to 2.01), Black (OR 1.58, 95% CI 1.04 to 2.41) and Other (OR 1.33, 95% CI 1.02 to 1.74) ethnicity were more likely to experience instability than White CYP. Deprivation was not a significant predictor of instability. Compared with congenital abnormalities, CYP with most other primary diagnoses had a higher risk of instability; only CYP with a primary perinatal diagnosis had significantly lower risk (OR 0.23, 95% CI 0.19 to 0.29).

Conclusions

The large number of CYP with LLCs who are unstable, deteriorating or dying may benefit from input from specialist paediatric palliative care. The age group under 1 and CYP of South Asian, Black and Other ethnicities should be priority groups.
Bleomycin-induced skin toxicity: is it always flagellate erythema?
Authors: Verma Shailendra Prasad , Subbiah Arunkumar , Kolar Vishwanath Vinod , Dutta Tarun Kumar
Published: September 2016

Bleomycin-induced skin toxicity is a rare and unique complication. We report a 35-year-old man with nodular lymphocytic predominant Hodgkin's lymphoma, stage IVB, who was started on adriamycin, bleomycin, vinblastin and dacarbazine (ABVD) chemotherapy. He developed pruritic hyperpigmented, patchy skin lesions on the neck, back, chest and thighs after IA cycle of ABVD chemotherapy. Lesions were not typical flagellate rash but hyperpigmented, patchy and mildly pruritic lesions over the trunk and proximal extremities. Lesions increased with continuation of bleomycin and improved gradually after removing the drug from chemotherapy schedule. The patient was in complete remission after VI cycles of chemotherapy (AVD Regimen) and skin lesions healed with minimal residual hyperpigmentation.
Online self-assessment of cardiovascular risk using the Joint British Societies (JBS3)-derived heart age tool: a descriptive study
Authors: Patel Riyaz S , Lagord Catherine , Waterall Jamie , Moth Martin , Knapton Mike , Deanfield John E
Published: September 2016

Objective

A modified version of the Joint British Societies (JBS3) ‘heart age’ tool was introduced online to broaden access to personalised risk assessment to the general population and encourage participation in the National Health Service (NHS) Health Check programme. This study reports on its early uptake and the profiles of those who used the self-assessment tool to determine their own cardiovascular risk.

Design

Observational, retrospective analysis of online tool use.

Setting

Between February and July 2015, user data collected from the NHS Choices website, where the tool was hosted, were analysed anonymously using standard analytic packages.

Results

The online tool landing page was viewed 1.4 million times in the first 5 months, with increased activity following limited media coverage. Of the 575 782 users completing the data journey with a valid ‘heart age’ result, their demographic and risk factor profiles broadly resembled the population of England, although both younger users and males (60%) were over-represented. Almost 50% and 79% did not know or enter their blood pressure or total cholesterol values, respectively. Estimated heart age was higher than chronological age for 79% of all users, and also for 69% of younger users under 40 years who are at low 10-year risk and not invited for NHS Health Checks.

Conclusions

These data suggest a high level of public interest in self-assessment of cardiovascular risk when an easily understood metric is used, although a large number of users lack awareness of their own risk factors. The heart age tool was accessed by a group not easily reached by conventional approaches yet is at high cardiovascular risk and would benefit most from early and sustained risk reduction. These are both important opportunities for interventions to educate and empower the public to manage better their cardiovascular risk and promote population-level prevention.
PR and how to do it
Authors: Sheridan Libby
Published: September 2016

Public relations or PR, which focuses on building positive reputations, hasn't always had the best reputation itself. However, done right it can increase customer numbers and the uptake of services while also promoting a positive view of your practice. Libby Sheridan outlines what PR opportunities are, what they can do for your practice and how to get started.
How close are we to standardised extendedRASgene mutation testing? The UK NEQAS evaluation
Authors: Richman Susan D , Fairley Jennifer , Butler Rachel , Deans Zandra C
Published: September 2016

Aims

Since 2008,KRASmutation status in exon 2 has been used to predict response to anti-EGFR therapies. Recent evidence has demonstrated thatNRASstatus is also predictive of response. Several retrospective ‘extendedRAS’ analyses have been performed on clinical trial material. Despite this, are we really moving towards such extended screening practice in reality?

Methods

Data were analysed from four consecutive UK National External Quality Assessment Service for Molecular Genetics Colorectal cancer External Quality Assessment schemes (during the period 2014–2016), with up to 110 laboratories (worldwide) participating in each scheme. Testing of four or five tumour samples is required per scheme. Laboratories provided information on which codons were routinely screened, and provided genotyping and interpretation results for each sample.

Results

At least 85% of laboratories routinely testedKRAScodons 12, 13 and 61. Over the four schemes, an increasing number of laboratories routinely testedKRAScodons 59, 117 and 146. Furthermore, more laboratories were introducing next generation sequencing technologies. The pattern of ‘extended testing’ was reassuringly similar forNRAS, although fewer laboratories currently test for mutations in this gene. Alarmingly, still only 36.1% and 24.1% of participating laboratories met the ACP Molecular Pathology and Diagnostics Group and American Society of Clinical Oncology guidelines, respectively, for extendedRAStesting in the latest assessment.

Conclusions

Despite recommendations in the UK and USA on extendedRAStesting, there has clearly been, based on these results, a delay in implementation. Inadequate testing results in patients being subjected to harmful treatment regimens, which would not be the case, were routine practice altered, in line with evidence-based guidelines.
Regression grading in neoadjuvant treated pancreatic cancer: an interobserver study
Authors: N Kalimuthu Sangeetha , Serra Stefano , Dhani Neesha , Hafezi-Bakhtiari Sara , Szentgyorgyi Eva , Vajpeyi Rajkumar , Chetty Runjan
Published: September 2016

Aim

Several regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems.

Methods

Four gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7–20 slides from each case) of neoadjuvant chemoradiation-treated PDAC. A postscoring discussion with each pathologist was conducted. The results were entered into a standardised data collection form and statistical analyses were performed.

Results

There was little concordance across the three systems. The Kendall coefficient of concordance agreement scores were: CAP: 2-poor, 2-fair; Evans: 1-fair, 1-moderate, 2-good; MDA: 1-poor, 2-moderate, 1-good. Interpretation in all three grades in the CAP grading system was a source of discrepancy. Furthermore, using fibrosis as a criterion to assess regression was contentious. In the Evans system, quantifying tumour destruction using arbitrary percentage cut-offs (ie, 9% vs 10%; 50% vs 51%, etc) was imprecise and subjective. Although the MDA system generated greatest concordance, this was due to ‘oversimplification’ surrounding wide, arbitrarily assigned thresholds of </> 5% of tumour.

Conclusions

All systems lacked precision and clarity for accurate regression grading. Presently the clinical utility and impact of histological regression grading in patient management is questionable. There is a need to re-evaluate regression grading in the pancreas and establish a reproducible, clinically relevant grading system.
Explaining socioeconomic inequalities in self-rated health: a systematic review of the relative contribution of material, psychosocial and behavioural factors
Authors: Moor Irene , Spallek Jacob , Richter Matthias
Published: September 2016

Background

Material, psychosocial and behavioural factors are important explanatory pathways for socioeconomic inequalities in health. The aim of this systematic review was to summarise the available evidence on empirical studies and to analyse the relative contribution of these factors for explaining inequalities in self-rated health.

Methods

The study was performed in compliance with PRISMA guidelines. The literature search was conducted in the electronic databases PubMed and Web of Science (1996–2016) as well as by screening of reference lists of obtained articles. Two reviewers performed the search and critical appraisal of the studies. All studies that focus on explaining socioeconomic inequalities in self-rated health, including at least 2 of the 3 main pathways and analysing the relative contribution of these approaches in separate and joint models, were included.

Results

Eleven publications were included. Separate analyses showed that material, psychosocial and behavioural factors contribute to the explanation of socioeconomic inequalities in self-rated health. However, the combined analyses revealed that material factors contributed most to differences in self-rated health because of their higher independent (direct) effect and additional shared (indirect) effect (through psychosocial and behavioural factors). These results were largely independent of age, gender and indicator of socioeconomic status.

Conclusions

The evidence presented might be used for policymakers to identify and to justify prioritisation in terms of prevention and health promotion. The findings show that multiple factors are important for tackling social inequalities in health. Strategies for reducing these inequalities should focus on material/structural living conditions as they shape conditions of psychosocial resources and health behaviour.
Republished: Use of aspirin as sole oral antiplatelet therapy in acute flow diversion for ruptured dissecting aneurysms
Authors: Chiu Albert Ho Yuen , Ramesh Rajalakshmi , Wenderoth Jason , Davies Mark , Cheung Andrew
Published: September 2016

Subarachnoid hemorrhage secondary to rupture of a circumferential dissecting aneurysm continues to be a treatment dilemma. Vessel sacrifice, when possible, continues to be the safest option but in certain cases this is not possible due to lack of collateral supply. In such cases, coil assisted endovascular flow diversion has become a potential option but the requirement for dual antiplatelet therapy in an unsecured intracranial aneurysm continues to raise concern.

We present a 48-year-old man with a World Federation of Neurological Surgeons grade 5 subarachnoid hemorrhage, secondary to a ruptured intradural left vertebral artery dissecting aneurysm, who was treated successfully with a pipeline embolization device with Shield technology using aspirin and a single intravenous loading dose of abciximab. To our knowledge, this is the first case of an acute flow diversion performed using only aspirin as the sole oral antiplatelet agent.
Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes
Authors: Fares Hassan , DiNicolantonio James J , O'Keefe James H , Lavie Carl J
Published: September 2016

Objectives

Hypertension is well established as a major risk factor for cardiovascular disease. Although there is undeniable evidence to support the beneficial effects of antihypertensive therapy on morbidity and mortality, adequate blood pressure management still remains suboptimal. Research into the treatment of hypertension has produced a multitude of drug classes with different efficacy profiles. These agents include β-blockers, diuretics, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers. One of the oldest groups of antihypertensives, the calcium channel blockers are a heterogeneous group of medications.

Methods

This review paper will focus on amlodipine, a dihydropyridine calcium channel blockers, which has been widely used for 2 decades.

Results

Amlodipine has good efficacy and safety, in addition to strong evidence from large randomised controlled trials for cardiovascular event reduction.

Conclusions

Amlodipine should be considered a first-line antihypertensive agent.
Clinical characteristics of canine fibrocartilaginous embolic myelopathy (FCE): a systematic review of 393 cases (1973–2013)
Authors: Bartholomew K. A. , Stover K. E. , Olby N. J. , Moore S. A.
Published: September 2016

Fibrocartilaginous embolic myelopathy (FCE) is common in dogs; however, there is conflicting information in the veterinary literature regarding clinical characteristics and data on recovery in severe cases is sparse. A systematic review of canine FCE was performed to delineate the natural history of this disease. 322 previously reported cases and 71 previously unreported cases were identified for inclusion. Source publications were identified via PubMed central search and by references from review articles. Previously unreported cases were identified via computerised medical records search at two veterinary institutions. FCE was most common in middle‐aged large breed dogs (30 per cent); however, the miniature schnauzer was the most frequently reported individual breed and small breeds comprised 24 per cent of all reported cases. The most common neuroanatomical localisation was a T3‐L3 myelopathy (33.1 per cent). Prognosis for recovery of ambulation was good to excellent with 85 per cent of cases regaining the ability to walk unassisted, most within 3 weeks. Persistent neurological deficits were common in patients that recovered ambulation (49.1 per cent). When nociception was absent in the affected limbs at initial presentation, rate of recovery was lower (10 per cent); however, this data is likely biased by limited follow‐up in more severe cases. Future prospective studies should evaluate prognosis for more severely affected patients.
Brook trout use of thermal refugia and foraging habitat influenced by brown trout
Authors: Hitt Nathaniel P. , Snook Erin L. , Massie Danielle L.
Published: September 2016

The distribution of native brook trout (Salvelinus fontinalis) in eastern North America is often limited by temperature and introduced brown trout (Salmo trutta), the relative importance of which is poorly understood but critical for conservation and restoration planning. We evaluated effects of brown trout on brook trout behavior and habitat use in experimental streams across increasing temperatures (14–23 °C) with simulated groundwater upwelling zones providing thermal refugia (6–9 °C below ambient temperatures). Allopatric and sympatric trout populations increased their use of upwelling zones as ambient temperatures increased, demonstrating the importance of groundwater as thermal refugia in warming streams. Allopatric brook trout showed greater movement rates and more even spatial distributions within streams than sympatric brook trout, suggesting interference competition by brown trout for access to forage habitats located outside thermal refugia. Our results indicate that removal of introduced brown trout may facilitate native brook trout expansion and population viability in downstream reaches depending in part on the spatial configuration of groundwater upwelling zones.
Global analysis of π± and K± fragmentation functions and their application to top quark decays considering new BABAR and Belle experimental data
Authors: Nejad S. Mohammad Moosavi , Soleymaninia M. , Khorramian A.N.
Published: September 2016

Recently, the Belle and BABAR collaborations published the single-inclusive electron–positron annihilation data at the center of mass energies ([Formula: see text]) of 10.52 and 10.54 GeV, respectively. These new data offer one the possibility to determine the nonperturbative initial conditions of fragmentation functions (FFs) much more accurately. Here, we extract the FFs of π± and K± particles at next-to-leading order (NLO) including these new data, which are in the regions of larger scaled-energy z and lower [Formula: see text]. However, the π± and K± FFs were calculated previously, but our new analysis shows that adding these new data, for instance, changes the (u, s) → π+ FFs in the large-z region while the s → π+ FF is also changed at low z. These new data also change the u → K+ FF at low z (z < 0.2) more than at large z, but the d → K+ FF is affected at z > 0.07. The FF of g → K+ is decreased everywhere, for example, about 25% at z = 0.01. We also apply, for the first time, the extracted FFs to make our predictions for the scaled-energy distributions of π± and K± inclusively produced in top quark decays at NLO.
Optimization Techniques for CNT Based VLSI Interconnects — A Review
Authors: Karthikeyan A. , Mallick P. S.
Published: September 2016

Interconnects plays an important role in integrated circuits. Copper is used as an interconnect material, but beyond 22[Formula: see text]nm technology node it faces many problems due to grain boundary scattering, and therefore carbon nanotubes are the most promising future interconnect materials. Various techniques and approaches such as driver sizing, repeater sizing, repeater insertion, wire sizing, wire spacing, shielding, boos table repeater were used by various researchers. Many of these techniques can be utilized for future CNT based VLSI interconnects as well. This paper presents a detailed discussion on the techniques and approaches of past, present and future relevant for interconnects of VLSI circuits.
An Attribute-Based Development Framework of Node Software for Various Operating Systems in Sensor Network Environment
Authors: Lee Woojin , Choi Ilwoo , Song Cheeyang , Kim Juil
Published: September 2016

This paper proposes a framework for the development of sensor node software for various operating systems in a sensor network environment. The proposed development framework consists of attributes, code templates and development support tool. Sensor node software is developed, based on the framework through four steps —sensor network modeling, PIM design, PSM design and code generation. Accordingly, this paper presents the methods for attributes design, code templates design, PIM-to-PSM mapping, and source code generation. Through the proposed technique, reusability of sensor network software will be increased since models, attributes and code templates can be reused for various operating systems through the framework. Productivity of software development will be increased, because software design is easily performed using attributes and software codes for all nodes in the sensor network can be generated at once from a model. Also, expandability of sensor network software will be increased, since new functions of existing operating systems or new operating systems can be added through the framework and sensor network software can be rebuilt by applying the added functions or operating systems.
Multi-Resource Modeling of Real-Time Software Based on Resource Timed Process Algebra
Authors: Zhu Yi , Huang Zhiqiu , Zhang Guangquan , Zhou Hang , Xiao Fangxiong
Published: September 2016

With the process of non-functional properties research on real-time systems, multi-resource estimation and analysis of real-time systems become a hotspot. Process algebra is a formal method that is fit for analyzing the functional properties of real-time systems, but it cannot analyze the multi-resource properties. Resource timed process algebra (RTPA) proposed in this paper can handle it efficiently by extending multi-resource semantics on timed communicating sequential process (TCSP). The multi-resource consumption of real-time instruction is mapped into the resource vector of RTPA, and then the multi-resource consumption of real-time systems can be modeled and optimized by using RTPA; the resource optimal checking algorithms are proposed to check the multi-resource satisfiability of instructions and calculate the minimum resource and accumulated resource of real-time systems. This formal method improves the accuracy and efficiency of multi-resource calculation, and the calculation results can be further used to quantitatively analyze and optimize the multi-resource consumption of real-time systems.
Semicomplete Finite p-Groups of Class 2
Authors: Shabani Attar M.
Published: September 2016

Let G be a group and G' be its commutator subgroup. An automorphism α of a group G is called an IA-automorphism if x-1α(x) ∈ G' for each x ∈ G. The set of all IA-automorphisms of G is denoted by IA (G). A group G is called semicomplete if and only if IA (G)= Inn (G), where Inn (G) is the inner automorphism group of G. In this paper we completely characterize semicomplete finite p-groups of class 2; we also classify all semicomplete finite p-groups of order pn(n ≤ 5), where p is an odd prime. This completes our work in 2011.
On Nilpotent Finite Alternative Rings with Planar Zero-Divisor Graphs
Authors: Kuzmina A. S.
Published: September 2016

In this paper we prove that any finite nilpotent alternative ring with planar zero-divisor graph is associative.
Great Lakes Water Levels: Decomposing Time Series for Attribution
Authors: Pietrafesa Leonard J. , Bao Shaowu , Huang Norden E. , Gayes Paul T. , Yan Tingzhuang , Slattery Michael P.
Published: September 2016

Great Lakes water levels have been trending downwards throughout the 20th and into the 21st centuries. Potential causes are numerous. There have been dredging and water diversion projects over the last 110 years, increasing demand for fresh water consumption from a rising population, and considerable variations in environmental factors (rainfall, snowfall, air temperature, and wind), all causal in nature. A thorough assessment of the National Ocean and Atmospheric Administration (NOAA) National Center for Environmental Information (NCEI) and the NOAA National Centers for Environmental Prediction and the National Center for Atmospheric Research (NCEP/NCAR) — Reanalysis Project (RP) archives of time series of winds, air temperatures, rainfall and snowfall, and water level data, reveals that falling lake levels can be linked to rising air temperatures. Nonuniform, post-glacial, isostatic adjustments of the entire Great Lakes region has further complicated the system as land mass tilting causes localized uplift or subsidence that has also altered relative water levels. A mathematical decomposition of the various data sets and accessory calculations strongly indicate regional atmospheric temperature increases over the entire 20th century and the early 21st century resulting in increased evaporation, appears to be the dominant driving factor in the continued downward trend of water levels in the Great Lakes. Moreover, a high degree of correlation was discovered in comparing water level in the Great Lakes with the comparable temporal variability and record length trends evident both the Global (Land and Ocean) Surface Temperature Anomaly (GSTA) time series and the Atlantic Multidecadal Oscillation (the AMO). It is of note that there have been several water level events since 2013 from which the long term losses of fresh water have undergone a change and the lakes have gained fresh water. This presents an apparent quandary to our nearly 120 year, record length study which revealed downward trends in water levels. To wit, this recent upward movement begs the question: Is the two-year change a precursor to increases in water levels or is it just a local blip? We will focus on data up to 2013, but comment upon recently reported increases as part of our analyses.
The role of geoarchaeology in the preservation and management of the Theban Necropolis, West Bank, Egypt
Authors: Aubry Marie-Pierre , Dupuis Christian , Berggren William A. , Ghaly Holeil , Ward David , King Chris , Knox Robert W. O'B. , Ouda Khaled , Youssef Moustafa
Published: September 2016

A World Heritage Site since 1979, the Theban Necropolis was built by the Pharaohs of the 18th to 20th Dynasties (
c.
1539 – 1075 BCE). A variety of pharaonic (and lesser nobles') tombs, funerary temples and sanctuaries were located/excavated in the lower part of the
c.
400 m high pyramidal El Qurn in a variety of lithofacies (predominantly marine limestones and shales). These monuments are located in regionally persistent structural entities as well as gravitational collapse structures (GCS) whose probable origin and timing are reviewed and updated here, based on information that was unavailable to us at the time of writing a complementary paper in 2008 (but only published in 2015). We review here the historical development of the Theban Necropolis in the framework of the geological and geomorphological landscape and the first geological map of the region prepared by our Working Group for the Theban International Geoarcheological Project (TIGA) in 2011. We conclude with a preferential prioritizing of the perceived short- and long-term threats to the preservation of the Theban Necropolis and its monuments: least vulnerable to destabilization are the Valley of the Kings, Valley of the Queens, Block of Sheik Abdel Qurnah – El Khokkah; more vulnerable are Deir El Medina, Qunet Mura'I and El Assasif; most vulnerable are the Village of the Workers, Deir El Bahari and the Valley of the Colors. Accordingly it will be necessary to devise geotechnical solutions to prevent the destruction of (at least) some of the monuments under consideration here.
Geological map fusion: OneGeology-Europe and INSPIRE
Authors: Laxton J. L.
Published: September 2016

Geological maps can be seen as a type of model and can be implemented in digital systems as geological spatial databases. In this context, geological map fusion can be implemented at different levels: harmonization of the conceptual data model describing the map objects; the use of shared concepts to describe properties in the model to give semantic harmonization; and ensuring geometric consistency. GeoSciML has been developed as an interchange language for geosciences information, derived from a common conceptual data model, along with common vocabularies of concepts to populate the object properties. GeoSciML and the vocabularies were used in the OneGeology-Europe project where a 1:1 million scale geological map of Europe was delivered using disseminated web services from 20 different data providers. The lessons learnt from the OneGeology-Europe project informed the development of the INSPIRE Geology Data Specification. The INSPIRE data specification is used to define what information must be made available through web services under the INSPIRE legislation, so has to be kept simple. The INSPIRE data model can be extended with GeoSciML and will provide a basis for geological map fusion.