bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of body mass index with efficacy of exenatide twice daily added to insulin glargine in patients with type 2 diabetes
Authors: Wolffenbuttel B. H. R. , Van Gaal L. , Durán‐Garcia S. , Han J.
Published: March 2016

This post hoc analysis assessed the evidence behind common reimbursement practices by evaluating the relationship of body mass index (BMI) ranges (<30, 30–35 and >35 kg/m2) with treatment effects of exenatide twice daily among patients with type 2 diabetes. Patients received exenatide twice daily added to insulin glargine in two 30‐week studies (exenatide twice daily vs insulin lispro, n = 627; exenatide twice daily vs placebo, n = 259). No association of baseline BMI with changes in efficacy variables was observed. Glycated haemoglobin (HbA1c) reductions were significant (p < 0.0001) and similar across BMI range groups in the lispro‐comparator study and greater for exenatide versus placebo in the placebo‐controlled study. Significant weight loss occurred with exenatide across BMI range groups (p < 0.0001), while weight increased with both comparators. Achievement of HbA1c <7.0% (<53 mmol/mol) without weight gain was greater for exenatide versus comparators. Systolic blood pressure decreased across BMI range groups with exenatide in the lispro‐comparator study (p < 0.0001); changes in lipids were not clinically meaningful. Minor hypoglycaemia was less frequent for exenatide versus insulin lispro. These findings suggest that BMI alone should not limit clinical decision‐making or patient access to medication.
Dual antiplatelet therapy after stroke or transient ischaemic attack – how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta‐analysis
Authors: Ge F. , Lin H. , Liu Y. , Li M. , Guo R. , Ruan Z. , Chang T.
Published: March 2016

Background and purpose

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 90 days was recommended as the secondary prevention of minor ischaemic strokes or transient ischaemic attacks (TIAs) in 2014. However, whether the duration of 90 days is optimal for each patient remains unclear. Therefore, the efficacy and safety of short‐term (≤3 months) and prolonged (≥1 year) DAPT after stroke or TIA were assessed via a systematic review and meta‐analysis.

Methods

The Cochrane Library, Clinical Trials.gov and PubMed were searched up to December 2014 and nine randomized controlled trials were included involving 21 923 patients.

Results

Short‐term DAPT significantly reduced the risk of ischaemic stroke recurrence by 41% and major vascular events by 30%, without increasing the risk of intracranial haemorrhage. Prolonged DAPT reduced the risk of ischaemic stroke recurrence by 12% and major vascular events by 10%. However, the risk of major bleeding and intracranial haemorrhage increased.

Conclusions

Short‐term DAPT appears to be superior to prolonged DAPT. However, the difference in efficacy outcome needs to be carefully explained and confirmed by further well‐designed randomized controlled trials.
Small temporal pole encephalocele: A hidden cause of “normal” MRI temporal lobe epilepsy
Authors: Toledano Rafael , Jiménez‐Huete Adolfo , Campo Pablo , Poch Claudia , García‐Morales Irene , Gómez Angulo Juan Carlos , Coras Roland , Blümcke Ingmar , Álvarez‐Linera Juan , Gil‐Nagel Antonio
Published: March 2016

Objective

Small temporal pole encephalocele (STPE) can be the pathologic substrate of epilepsy in a subgroup of patients with noninformative magnetic resonance imaging (MRI). Herein, we analyzed the clinical, neurophysiologic, and radiologic features of the epilepsy found in 22 patients with STPE, and the frequency of STPE in patients with refractory focal epilepsy (RFE).

Methods

We performed an observational study of all patients with STPE identified at our epilepsy unit from January 2007 to December 2014. Cases were detected through a systematic search of our database of RFE patients evaluated for surgery, and a prospective collection of patients identified at the outpatient clinic. The RFE database was also employed to analyze the frequency of STPE among the different clinical subgroups.

Results

We identified 22 patients with STPE (11 women), including 12 (4.0%) of 303 patients from the RFE database, and 10 from the outpatient clinic. The median age was 51.5 years (range 29–75) and the median age at seizure onset was 38.5 years (range 15–73). Typically, 12 (80%) of 15 patients with left STPE reported seizures with impairment of language. Among the RFE cases, STPE were found in 9.6% of patients with temporal lobe epilepsy (TLE), and in 0.5% of those with extra‐TLE (p = 0.0001). STPEs were more frequent in TLE patients with an initial MRI study reported as normal (23.3%) than in those with MRI‐visible lesions (1.4%; p = 0.0002). Stereo‐electroencephalography was performed in four patients, confirming the localization of the epileptogenic zone at the temporal pole with late participation of the hippocampus. Long‐term seizure control was achieved in four of five operated patients.

Significance

STPE can be a hidden cause of TLE in a subgroup of patients with an initial report of “normal” MRI. Early identification of this lesion may help to select patients for presurgical evaluation and tailored resection.
Understanding the Formation of Consumers' Stock Market Expectations
Authors: Chin Alycia , Bruine De Bruin Wändi
Published: March 2016

To understand consumers' investment decisions, national surveys such as the Health and Retirement Study elicit consumers' expectations about stock market movements. Analyses of stock market expectations show substantial heterogeneity between consumers. It is commonly speculated that this heterogeneity reflects variations in the beliefs underlying consumers' stock market expectations, that is, their “mental models.” In an online survey of American adults, we find that consumers think about different economic and political issues when generating stock market expectations for the next year. Regardless of the specific issues on which consumers focused, however, their assessments of the issues seemed to reflect a single underlying perception of changes in economic conditions. Regression analyses show that variation in stock market expectations is related to consumers' overall assessments of economic developments. We discuss the implications of these results for economic surveys and investment communications.
Effect of occlusal vertical dimension on swallowing patterns and perioral electromyographic activity
Authors: MacAvoy S. K. , Jack H. C. , Kieser J. , Farella M.
Published: March 2016

Abnormal swallow patterns have been associated with specific dentofacial traits, such as an anterior open bite, but the cause–effect relationship between swallowing and malocclusion remains highly controversial. The aim of this research was to determine the effects of acute change in occlusal vertical dimension (OVD) on intraoral pressure swallow patterns and perioral electromyographic activity (EMG) during swallowing. Ten volunteers (five female, five male; 27–32 years) repeated standardised swallowing tasks as the OVD was progressively increased using mandibular trays of different heights. Standardised swallowing tasks were performed repetitively with each tray in place. Individual swallowing waveforms were quantitatively and qualitatively analysed. Peak pressure, swallow duration, time to peak pressure and lip EMG peak activity were assessed for each swallow. Data were analysed using mixed‐model analysis. As OVD increased, lip peak pressure during swallowing increased almost threefold (+2·1 kPa; P ≤ 0·001), whereas swallow duration increased by 12·7 per cent (+160 ms; P = 0·01) at lip level and by 26·4 per cent (+270 ms; P < 0·001) at tongue level. Perioral muscle activity during swallows increased by 43·7 per cent (P ≤ 0·01) up to the OVD where resting lip seal was not attainable. Swallowing waveforms varied markedly between individuals, but interindividual waveforms were only minimally affected. The adaptive response and the waveform similarities associated with OVD variation supports the existence of a central control mechanism for swallowing, which may be modified by peripheral inputs.
Determination of mammalian deoxyribonucleic acid (DNA) in commercial vegetarian and vegan diets for dogs and cats
Authors: Kanakubo K. , Fascetti A. J. , Larsen J. A.
Published: March 2016

The determination of undeclared ingredients in pet food using different analytical methods has been reported in recent years, raising concerns regarding adequate quality control, dietary efficacy and the potential for purposeful adulteration. The objective of this study was to determine the presence or absence of mammalian DNA using multiplex polymerase chain reaction (PCR) on diets marketed as vegetarian or vegan for dogs and cats. The diets were tested in duplicate; two samples were purchased approximately 3 to 4 months apart with different lot numbers. Multiplex PCR‐targeted mitochondrial DNA with two species‐specific primers was used to amplify and sequence two sections of the cytochrome b gene for each of the 11 mammalian species. Half of the diets assessed (7/14) were positive for one or more undeclared mammalian DNA source (bovine, porcine, or ovine), and the result was repeatable for one or more species in six diets. While most of the detected DNA was found at both time points, in some cases, the result was positive only at one time point, suggesting the presence may have been due to unintentional cross‐contact with animal‐sourced ingredients. DNA from feline, cervine, canine, caprine, equine, murine (mouse and rat) and leporine was not identified in any samples. However, evidence of mammalian DNA does not confirm adulteration by the manufacturer nor elucidate its clinical significance when consumed by animals that may benefit from a vegetarian or vegan diet.
Effects of Vocational Training on a Group of People with Intellectual Disabilities
Authors: Gomes‐Machado Maria Luiza , Santos Flavia Heloisa , Schoen Teresa , Chiari Brasilia
Published: March 2016

Intellectual disability (ID) is the most restraining disability for professional inclusion, mainly due to the lack of adaptive skills focused on the work environment observed in people with ID. The aims of this study were (i) to describe and analyze the effects of a vocational training program on the adaptive behavior of people with ID and (ii) to evaluate the social impact of employability on the life of the employees with ID. Participants were 43 people with mild or moderate ID, age between 18 and 28 years. The Supports Intensity Scale was applied at two stages: T1‐PRETRAINING and T2‐POSTTRAINING, while the Social Impact Questionnaire was used at the third stage, after employment (T3 POSTINCLUSION). The authors found that there were differences in total scores between stages T1 and T2 in relation to all the adaptive skills assessed, with a reduction of around 50% in the need for support. One year after inclusion in the labor market (T3), participants were still employed, with significant improvements in such aspects as learning, autonomy, affective and social development, as well as in family and community relations. The vocational training contributed to the global development of persons, favoring their professional inclusion, and as a result, sustenance, autonomy, and a decrease in the need for assistance and support.
Riots and a blank canvas: young people creating texts, creating spaces
Authors: McIntyre Joanna
Published: March 2016

This article draws on research into the work of Greenshoots, a small company of creative practitioners who provide opportunities for young people to work on projects involving visual and creative practices with a strong link to local heritage. Two specific projects form the focus of the paper: Riot and Blank Canvas. Both aimed to provide opportunities for young people to work with professional artists and performers to create a site‐specific exhibition and performance in a disused warehouse space on the edge of the developing Creative Quarter in Nottingham. The projects took place out of school, and the research focused on the creative processes and practices involved in the production of texts created by the young people as they inhabited the space and developed, within a community of peers and artists, representations of that urban space. This article explores the ways in which the projects open up the potential for young people to engage with literacy practices, which traverse the boundaries of space, of art forms and of notions of culture and heritage. Two theoretical frames are used in the paper: Lave and Wenger's “legitimate peripheral participation” (1991) and various scholars' explorations of place‐based approaches. In this way, the article aims to contribute to understandings of the diverse roles and potentials of young peoples' creative practices and literacies in and out of school contexts.
A comparative study using WHO and binary oral epithelial dysplasia grading systems in actinic cheilitis
Authors: Câmara PR , Dutra SN , Takahama Júnior A , Fontes KBFC , Azevedo RS
Published: March 2016

Objective

To evaluate comparatively the influence of histopathological features on epithelial dysplasia (ED) and the effectiveness in usage of WHO and binary grading systems in actinic cheilitis (AC).

Material and methods

Cytological and architectural alterations established by WHO for ED were evaluated in 107 cases of AC. Epithelial dysplasia was graded using WHO and binary systems. The comparisons were performed using kappa, chi‐square, and phi coefficient tests (P < 0.05).

Results

Most cases were classified as mild ED (44.5%) in the WHO system and as low risk for malignant transformation (64.5%) in the binary system. There was a positive correlation between WHO and binary systems (k = 0.33; P < 0.0002). Loss of basal cell polarity (P < 0.001) was associated with severity of ED grade in the WHO system. Anisonucleosis (P < 0.0001), nuclear pleomorphism (P < 0.0001), anisocytosis (P = 0.03), cell pleomorphism (P = 0.002) increased nuclear/cytoplasm ratio (P < 0.0001), increased nuclear size (P < 0.0001), increased number of mitotic figures (P = 0.0006), and dyskeratosis (P = 0.008) were associated with severity of ED grade in the binary system.

Conclusions

It seems that usage of binary ED grading system in AC may be more precise because there is correlation between many of cytological and some of architectural microscopic alterations with increased grade of ED.
Fertility Assessment in Sorraia Stallions by Sperm‐Fish and Fkbp6 Genotyping
Authors: Kjöllerström HJ , do Mar Oom M , Chowdhary BP , Raudsepp T
Published: March 2016

Contents

The Sorraia, a critically endangered indigenous Iberian horse breed, is characterized by low genetic variability, high rate of inbreeding, bad sperm quality and subfertility. Here, we studied 11 phenotypically normal but subfertile Sorraia stallions by karyotyping, sex chromosome sperm‐FISH and molecular analysis of FKBP6 – a susceptibility locus for impaired acrosome reaction (IAR). The stallions had normal sperm concentration (>300 million cells/ml), but the numbers of progressively motile sperm (21%) and morphologically normal sperm (28%) were invariably low. All stallions had a normal 64,XY karyotype. The majority of sperm (89%) had normal haploid sex chromosome content, although 11% of sperm carried various sex chromosome aneuploidies. No correlation was found between the percentage of sperm sex chromosome abnormalities and inbreeding, sperm morphology or stallion age. Direct sequencing of FKBP6 exon 4 for SNPs g.11040315G>A and g.11040379C>A revealed that none of the stallions had the susceptibility genotype (A/A‐A/A) for IAR. Instead, all animals had a G/G‐A/A genotype – a testimony of low genetic variability. The findings ruled out chromosomal abnormalities and genetic predisposition for IAR as contributing factors for subfertility. However, low fertility of the Sorraia stallions could be partly attributed to relatively higher rate of sex chromosome aneuploidies in the sperm.
Pre‐transplant end‐stage renal disease‐related immune risk profile in kidney transplant recipients predicts post‐transplant infections
Authors: Crepin T. , Gaiffe E. , Courivaud C. , Roubiou C. , Laheurte C. , Moulin B. , Frimat L. , Rieu P. , Mousson C. , Durrbach A. , Heng A.‐E. , Saas P. , Bamoulid J. , Ducloux D.
Published: March 2016

Background

End‐stage renal disease (ESRD) is associated with premature aging of the T‐cell system. Nevertheless, the clinical significance of pre‐transplant ESRD‐related immune senescence is unknown.

Methods

We studied whether immune risk phenotype (IRP), a typical feature of immune senescence, may affect post‐transplant infectious complications. A total of 486 patients were prospectively studied during the first year post transplant. IRP was defined as positive cytomegalovirus serology with at least 1 of the following criteria: CD4/CD8 ratio <1 and/or CD8 T‐cell count >90th percentile.

Results

We found that 47 patients (9.7%) had pre‐transplant IRP. IRP+ patients did not differ from IRP− patients for any clinical characteristics, but exhibited more pronounced immune senescence. Both opportunistic infections (43% vs. 6%, P < 0.001) and severe bacterial infection (SBI) (40% vs. 25%, P = 0.028) were more frequent in IRP+ patients. In multivariate analysis, IRP was predictive of both opportunistic infection (hazard ratio [HR] 2.97 [95% confidence interval {CI} 1.53–5.76], P = 0.001), and SBI (HR 2.33 [95% CI 1.34–3.92], P = 0.008). Acute rejection rates were numerically much lower in IRP+ patients. A total of 418 patients (86%) had biological evaluation 1 year post transplant. Among 41 IRP+ patients, 35 (85%) remained IRP+ 1 year post transplant.

Conclusion

Pre‐transplant IRP is associated with an increased risk of post‐transplant infection.
Blood vessel occlusion in peri‐burn tissue is secondary to erythrocyte aggregation and mitigated by a fibronectin‐derived peptide that limits burn injury progression
Authors: Asif Bilal , Rahim Abdul , Fenner Justine , Lin Fubao , Hirth Douglas , Hassani John , McClain Steven A. , Singer Adam J. , Tonnesen Marcia G. , Clark Richard A.F.
Published: March 2016

Although vascular occlusion has long been noted in peri‐burn tissue, the literature is inconsistent regarding the nature of the occlusion, with articles in the 1940s claiming that erythrocytes were the culprit and in the 1980s–1990s that microthrombi were responsible. To better define the nature of vessel occlusion, we studied two porcine burn models, a hot comb horizontal injury model and a vertical injury progression model. In both cases, tissue from the first two days after burn were stained with hemotoxylin and eosin, or probed for platelets or for fibrinogen/fibrin. Erythrocytes, identified as nonstained, clumped, anuclear, 5 µm cells, occluded most blood vessels (BVs) in both burn models. In contrast, platelet or fibrinogen/fibrin antibodies stained BV occlusions minimally at early time points, and only up to 16% of deep dermal BVs at 48 hours in the hot comb model and up to 7% at 24 hours in the vertical injury progression model. Treatment of animals with a fibronectin‐derived peptide (P12), which limits burn injury progression and can dilate peripheral microvasculature, reduced erythrocyte occlusion by at least 50%, speeded healing and reduced scarring. Early erythrocyte aggregation, rather than thrombosis, explains the ineffectiveness of anticoagulants to prevent burn injury progression.
Full-Scope Probabilistic Safety Assessment of Balakovo Unit 1 in Russia
Authors: Morozov Vladimir , Tokmachev Gennady , Lutsuk Rostislav , Kopylov Sergey
Published: March 2016

The Balakovo Nuclear Power Plant operating in Russia has four operating units of a VVER-1000 type. The first unit was connected to the grid on Dec. 28, 1985, and put in commercial operation on May 23, 1986. According to modern requirements of the Russian Nuclear Regulatory Authority, the full-scope probabilistic safety assessment (PSA) must be performed to extend the license for operation beyond an initial 30-year lifetime of the unit. The paper presents the results of the Level 1 PSA covering internal initiating events for power and shutdown operational plant states, internal hazards (fires and floods), and external hazards, including natural and man-made events, in particular, seismic impact, and aircraft crash.
Implementation of atomic layer etching of silicon: Scaling parameters, feasibility, and profile control
Authors: Ranjan Alok , Wang Mingmei , Sherpa Sonam D. , Rastogi Vinayak , Koshiishi Akira , Ventzek Peter L. G.
Published: March 2016

Atomic or layer by layer etching of silicon exploits temporally segregated self-limiting adsorption and material removal steps to mitigate the problems associated with continuous or quasicontinuous (pulsed) plasma processes: selectivity loss, damage, and profile control. Successful implementation of atomic layer etching requires careful choice of the plasma parameters for adsorption and desorption steps. This paper illustrates how process parameters can be arrived at through basic scaling exercises, modeling and simulation, and fundamental experimental tests of their predictions. Using chlorine and argon plasma in a radial line slot antenna plasma source as a platform, the authors illustrate how cycle time, ion energy, and radical to ion ratio can be manipulated to manage the deviation from ideality when cycle times are shortened or purges are incomplete. Cell based Monte Carlo feature scale modeling is used to illustrate profile outcomes. Experimental results of atomic layer etching processes are illustrated on silicon line and space structures such that iso-dense bias and aspect ratio dependent free profiles are produced. Experimental results also illustrate the profile control margin as processes move from atomic layer to multilayer by layer etching. The consequence of not controlling contamination (e.g., oxygen) is shown to result in deposition and roughness generation.
Functional assay of antiplatelet drugs based on margination of platelets in flowing blood
Authors: Eichinger Colin D. , Fogelson Aaron L. , Hlady Vladimir
Published: March 2016

A novel functional assay of antiplatelet drug efficacy was designed by utilizing the phenomena of platelet margination in flowing blood and transient platelet contacts with surface-immobilized platelet agonists. Flow margination enhances transient contacts of platelets with the walls of flow chambers covered with surface-immobilized proteins. Depending on the type and the surface density of the immobilized agonists, such transient interactions could “prime” the marginated platelet subpopulation for enhanced activation and adhesion downstream. By creating an upstream surface patch with an immobilized platelet agonist, platelet flow margination was used to test how effective antiplatelet drugs are in suppressing downstream platelet activation and adhesion. The platelet adhesion downstream was measured by a so-called “capture” patch region close to the distal end of the flow chamber. Platelet adhesion downstream was found to be dose-dependent on the upstream surface coverage of the “priming” patch, with immobilized fibrinogen acting as a platelet agonist. Several antiplatelet agents (acetylsalicylic acid, eptifibatide, and tirofiban) were evaluated for their efficacy in attenuating downstream adhesion after upstream platelet priming. The activation of the platelet population was found to be dependent on both the extent of the upstream agonist stimulus and the antiplatelet drug concentration. Such a relationship provides an opportunity to measure the efficacy of specific antiplatelet agents against the type and concentration of upstream platelet agonists.
Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-β clearance and aggregation in Alzheimer’s disease
Authors: Liu Chia-Chen , Zhao Na , Yamaguchi Yu , Cirrito John R. , Kanekiyo Takahisa , Holtzman David M. , Bu Guojun
Published: March 2016

Deleting neuronal heparan sulfates in a mouse model of Alzheimer’s disease results in faster Aβ clearance, reduced Aβ aggregation, and less amyloid pathology.
Somatic
PIK3CA
mutations as a driver of sporadic venous malformations
Authors: Castel Pau , Carmona F. Javier , Grego-Bessa Joaquim , Berger Michael F. , Viale Agnès , Anderson Kathryn V. , Bague Silvia , Scaltriti Maurizio , Antonescu Cristina R. , Baselga Eulàlia , Baselga José
Published: March 2016

PIK3CA
mutations induce venous malformations.
Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation
Authors: Masters Seth L. , Lagou Vasiliki , Jéru Isabelle , Baker Paul J. , Van Eyck Lien , Parry David A. , Lawless Dylan , De Nardo Dominic , Garcia-Perez Josselyn E. , Dagley Laura F. , Holley Caroline L. , Dooley James , Moghaddas Fiona , Pasciuto Emanuela , Jeandel Pierre-Yves , Sciot Raf , Lyras Dena , Webb Andrew I. , Nicholson Sandra E. , De Somer Lien , van Nieuwenhove Erika , Ruuth-Praz Julia , Copin Bruno , Cochet Emmanuelle , Medlej-Hashim Myrna , Megarbane Andre , Schroder Kate , Savic Sinisa , Goris An , Amselem Serge , Wouters Carine , Liston Adrian
Published: March 2016

A mutation in pyrin that disrupts regulation leads to autoinflammatory disease.
Emergence of a Large-Plaque Variant in Mice Infected with Coxsackievirus B3
Authors: Wang Yao , Pfeiffer Julie K.
Published: March 2016

Coxsackieviruses are enteric viruses that frequently infect humans. To examine coxsackievirus pathogenesis, we orally inoculated mice with the coxsackievirus B3 (CVB3) Nancy strain. Using HeLa cell plaque assays with agar overlays, we noticed that some fecal viruses generated plaques >100 times as large as inoculum viruses. These large-plaque variants emerged following viral replication in several different tissues. We identified a single amino acid change, N63Y, in the VP3 capsid protein that was sufficient to confer the large-plaque phenotype. Wild-type CVB3 and N63Y mutant CVB3 had similar plaque sizes when agarose was used in the overlay instead of agar. We determined that sulfated glycans in agar inhibited plaque formation by wild-type CVB3 but not by N63Y mutant CVB3. Furthermore, N63Y mutant CVB3 bound heparin, a sulfated glycan, less efficiently than wild-type CVB3 did. While N63Y mutant CVB3 had a growth defect in cultured cells and reduced attachment, it had enhanced replication and pathogenesis in mice. Infection with N63Y mutant CVB3 induced more severe hepatic damage than infection with wild-type CVB3, likely because N63Y mutant CVB3 disseminates more efficiently to the liver. Our data reinforce the idea that culture-adapted laboratory virus strains can have reduced fitness
in vivo
. N63Y mutant CVB3 may be useful as a platform to understand viral adaptation and pathogenesis in animal studies.

IMPORTANCE
Coxsackieviruses frequently infect humans, and although many infections are mild or asymptomatic, there can be severe outcomes, including heart inflammation. Most studies with coxsackieviruses and other viruses use laboratory-adapted viral strains because of their efficient replication in cell culture. We used a cell culture-adapted strain of CVB3, Nancy, to examine viral replication and pathogenesis in orally inoculated mice. We found that mice shed viruses distinct from input viruses because they formed extremely large plaques in cell culture. We identified a single mutation, VP3 N63Y, that was sufficient for large-plaque formation. N63Y mutant viruses have reduced glycan binding and replication in cell culture; however, they have enhanced replication and virulence in mice. We are now using N63Y mutant CVB3 as an improved system for viral pathogenesis studies.
Middle East Respiratory Syndrome Coronavirus NS4b Protein Inhibits Host RNase L Activation
Authors: Thornbrough Joshua M. , Jha Babal K. , Yount Boyd , Goldstein Stephen A. , Li Yize , Elliott Ruth , Sims Amy C. , Baric Ralph S. , Silverman Robert H. , Weiss Susan R.
Published: March 2016

Middle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. Like many coronaviruses, MERS-CoV carries genes that encode multiple accessory proteins that are not required for replication of the genome but are likely involved in pathogenesis. Evasion of host innate immunity through interferon (IFN) antagonism is a critical component of viral pathogenesis. The IFN-inducible oligoadenylate synthetase (OAS)-RNase L pathway activates upon sensing of viral double-stranded RNA (dsRNA). Activated RNase L cleaves viral and host single-stranded RNA (ssRNA), which leads to translational arrest and subsequent cell death, preventing viral replication and spread. Here we report that MERS-CoV, a lineage CBetacoronavirus, and related bat CoV NS4b accessory proteins have phosphodiesterase (PDE) activity and antagonize OAS-RNase L by enzymatically degrading 2′,5′-oligoadenylate (2-5A), activators of RNase L. This is a novel function for NS4b, which has previously been reported to antagonize IFN signaling. NS4b proteins are distinct from lineage ABetacoronavirusPDEs and rotavirus gene-encoded PDEs, in having an amino-terminal nuclear localization signal (NLS) and are localized mostly to the nucleus. However, the expression level of cytoplasmic MERS-CoV NS4b protein is sufficient to prevent activation of RNase L. Finally, this is the first report of an RNase L antagonist expressed by a human or bat coronavirus and provides a specific mechanism by which this occurs. Our findings provide a potential mechanism for evasion of innate immunity by MERS-CoV while also identifying a potential target for therapeutic intervention.

IMPORTANCEMiddle East respiratory syndrome coronavirus (MERS-CoV) is the first highly pathogenic human coronavirus to emerge since severe acute respiratory syndrome coronavirus (SARS-CoV). MERS-CoV, like other coronaviruses, carries genes that encode accessory proteins that antagonize the host antiviral response, often the type I interferon response, and contribute to virulence. We found that MERS-CoV NS4b and homologs from related lineage C bat betacoronaviruses BtCoV-SC2013 (SC2013) and BtCoV-HKU5 (HKU5) are members of the 2H-phosphoesterase (2H-PE) enzyme family with phosphodiesterase (PDE) activity. Like murine coronavirus NS2, a previously characterized PDE, MERS NS4b, can antagonize activation of the OAS-RNase L pathway, an interferon-induced potent antiviral activity. Furthermore, MERS-CoV mutants with deletion of genes encoding accessory proteins NS3 to NS5 or NS4b alone or inactivation of the PDE can activate RNase L during infection of Calu-3 cells. Our report may offer a potential target for therapeutic intervention if NS4b proves to be critical to pathogenesis inin vivomodels of MERS-CoV infection.
Xanthogranulomatous pancreatitis mimicking a malignant solid tumour
Authors: Atreyapurapu Viswanath , Keshwani Abhinav , Lingadakai Ramachandra , Pai Kanthilatha
Published: March 2016

Xanthogranulomatous inflammation, which is known to occur in several viscera, is rarely found to affect the pancreas. We report a case of xanthogranulomatous pancreatitis (XGP) occurring in a 60-year-old man who presented with epigastric pain and vomiting. Physical examination did not reveal any abnormality. Contrast-enhanced CT of the abdomen revealed an ill-defined, heterogeneous mass lesion in the uncinate process of the pancreas, suggestive of malignancy. Whipple's pancreaticoduodenectomy was performed and the final pathological diagnosis was XGP. The patient's postoperative course was uneventful. When a pancreatic mass does not show clinicoradiological features typical of common pancreatic neoplasms, XGP should be considered for a differential diagnosis and duodenum preserving surgery can be considered.
Clinical diagnostic dilemma in an uncharacteristic rapidly enlarging swelling of the anterior maxilla: extranodal diffuse large B cell lymphoma
Authors: Jayapalan Cheriyanthal Sisupalan , Pynadath Meera Kunjumon , Mangalath Ummar , George Antony , Aslam Sachin , Hafiz Abdul
Published: March 2016

Extranodal non-Hodgkin lymphoma (NHL) is infrequent in the oral cavity and constitutes 3.5% of oral cancers, and less than 2.2% of maxillofacial lymphomas. Diffuse large B cell lymphoma (DLBCL) accounts for 40% of NHL and has a 5-year survival rate of less than 30%. Early detection of extranodal NHL by dental personnel is extremely important as a delay in diagnosis can result in the cancer being diagnosed at an advanced stage and a poor prognosis. A 60-year-old male presented with an uncharacteristic asymptomatic rapidly enlarging swelling of the anterior maxilla, which on histopathological and immunohistochemical analysis was diagnosed as DLBCL. Imaging studies showed bone invasion and lymph node metastasis with poor prognosis. The patient received radiotherapy and chemotherapy but died within 3 months of diagnosis. A literature search revealed one another case with anterior maxilla occurrence, as the few oral DLBCL so far reported have appeared on the posterior palate or other intraoral sites.
Unusual organism causing pyocystis in an immunosuppressed haemodialysis patient
Authors: Elsayed Mohammad , Finn Arkadiy , Dapaah-Afriyie Kwame
Published: March 2016

A 68-year-old man with end-stage renal disease and a history of orthotopic cardiac transplantation on chronic immune suppression therapy presented to the emergency department with fever and purulent urethral discharge. He was diagnosed with pyocystis (bladder abscess). Culture of the urethral discharge showedTrueperella bernardiae. The patient improved after 3 days of bladder irrigation with normal saline and gentamicin. This case demonstrates that bladder abscess is a potential source of infection in an oliguric patient. This is the first report to describe the opportunistic pathogen,T. bernardiae, as the causative agent in pyocystis.
Emergency abdominal wall defects in neonates: saved by distress
Authors: Fawkner-Corbett David William , Shepherd Gregory , Lakhoo Kokila
Published: March 2016

This report presents two cases of neonatal patients with abdominal wall defects requiring emergency intervention, a closing gastroschisis and a pedunculated exomphalos with eviscerated liver. Both presented as pre-partum fetal distress and were delivered in a tertiary centre, where they received antenatal care. Coordination in the multidisciplinary team and prompt surgical intervention prevented loss of the eviscerated abdominal contents and prevented mortality in both cases.
Bilateral ureteric stones: an unusual cause of acute kidney injury
Authors: Sumner Daniel , Rehnberg Lucas , Kler Aaron
Published: March 2016

A 49-year-old man presented to the accident and emergency department, with a short history of vague abdominal pain, abdominal distension and two episodes of frank haematuria. A plain chest film showed dilated loops of large bowel and blood results on admission showed an acute kidney injury (stage 3). A diagnosis of bowel obstruction was made initially but a CT scan of the abdomen showed bilateral obstructing calculi. After initial resuscitation, the patient had bilateral ultrasound-guided nephrostomies and haemofiltration. He later underwent bilateral antegrade ureteric stenting. A decision will later be made on whether or not he is fit enough to undergo ureteroscopy and laser stone fragmentation.
Energy spectrum and wavefunction of electrons in hybrid superconducting nanowires
Authors: Kruchinin S. P.
Published: March 2016

Recent experiments have fabricated structured arrays. We study hybrid nanowires, in which normal and superconducting regions are in close proximity, by using the Bogoliubov–de Gennes equations for superconductivity in a cylindrical nanowire. We succeed to obtain the quantum energy levels and wavefunctions of a superconducting nanowire. The obtained spectra of electrons remind Hofstadter’s butterfly.
An extended form of Majid’s double biproduct
Authors: Ma Tianshui , Zheng Huihui
Published: March 2016

Let [Formula: see text] be a bialgebra. Let [Formula: see text] be a linear map, where [Formula: see text] is a left [Formula: see text]-module algebra, and a coalgebra with a left [Formula: see text]-weak coaction. Let [Formula: see text] be a linear map, where [Formula: see text] is a right [Formula: see text]-module algebra, and a coalgebra with a right [Formula: see text]-weak coaction. In this paper, we extend the construction of two-sided smash coproduct to two-sided crossed coproduct [Formula: see text]. Then we derive the necessary and sufficient conditions for two-sided smash product algebra [Formula: see text] and [Formula: see text] to be a bialgebra, which generalizes the Majid’s double biproduct in [Double-bosonization of braided groups and the construction of [Formula: see text], Math. Proc. Camb. Philos. Soc. 125(1) (1999) 151–192] and the Wang–Wang–Yao’s crossed coproduct in [Hopf algebra structure over crossed coproducts, Southeast Asian Bull. Math. 24(1) (2000) 105–113].
Non-Noetherian generalized Heisenberg algebras
Authors: Lopes Samuel A.
Published: March 2016

In this note, we classify the non-Noetherian generalized Heisenberg algebras [Formula: see text] introduced in [R. Lü and K. Zhao, Finite-dimensional simple modules over generalized Heisenberg algebras, Linear Algebra Appl. 475 (2015) 276–291]. In case deg [Formula: see text] > 1, we determine all locally finite and also all locally nilpotent derivations of [Formula: see text] and describe the automorphism group of these algebras.
Round weighting problem and gathering in radio networks with symmetrical interference
Authors: Bermond Jean-Claude , Huiban Cristiana Gomes , Reyes Patricio
Published: March 2016

In this paper, we consider the problem of gathering information in a gateway in a radio mesh access network. Due to interferences, calls (transmissions) cannot be performed simultaneously. This leads us to define a round as a set of non-interfering calls. Following the work of Klasing, Morales and Pérennes, we model the problem as a Round Weighting Problem (RWP) in which the objective is to minimize the overall period of non-interfering calls activations (total number of rounds) providing enough capacity to satisfy the throughput demand of the nodes. We develop tools to obtain lower and upper bounds for general graphs. Then, more precise results are obtained considering a symmetric interference model based on distance of graphs, called the distance-[Formula: see text] interference model (the particular case [Formula: see text] corresponds to the primary node model). We apply the presented tools to get lower bounds for grids with the gateway either in the middle or in the corner. We obtain upper bounds which in most of the cases match the lower bounds, using strategies that either route the demand of a single node or route simultaneously flow from several source nodes. Therefore, we obtain exact and constructive results for grids, in particular for the case of uniform demands answering a problem asked by Klasing, Morales and Pérennes.
A comprehensive performance evaluation framework of complex products based on a fuzzy AHP and DS theory
Authors: Li Yuhong , Gong Guanghong , Li Ni
Published: March 2016

With the development of computer technique, performance evaluation of complex products is playing an increasingly critical role in ensuring product quality and improving development process. An extensible comprehensive performance evaluation framework with the integration of effective group decision-making algorithms could be a supporting tool to achieve an efficient evaluation process and reduce comprehensive evaluation difficulty. This paper aims to provide a evaluation framework with friendly interactive operation and extensive expansibility, which adopts a multi-expert evaluation approach based on fuzzy, analytical hierarchy process (FAHP) and Dempstere–Shafer (DS) theory (FADS) in order to consider experts’ relative importance degree. In addition, an extensible evaluation process and related auxiliary functions are implemented in the framework, including the establishment of an assessment index system, integration and calls of multiple types of testing data preprocessing methods and index assessment methods suitable for small sample data, graphical result display and data analysis, etc. Finally, performance evaluation cases of two models of airborne radar anti-jamming are presented to verify the feasibility and expansibility of our assessment framework. The group decision-making method shows its effectiveness compared with the experimental evaluation results by the FAHP researched method.
SHORT RATE FORECASTING BASED ON THE INFERENCE FROM THE CIR MODEL FOR MULTIPLE YIELD CURVE DYNAMICS
Authors: HIN LIN-YEE , DOKUCHAEV NIKOLAI
Published: March 2016

In this paper, we propose a strategy to extract the information on the market participants’ expectation of the future short rate from the cross-sectional zero coupon bond prices. In line with the current market practice of building different yield curves for different tenors, we construct multiple one-factor short rate processes to pin down the salient features of the yield curve at different tenors. We represent this information in the form of the Cox–Ingersoll–Ross model implied parameters, and show that this information can be used to forecast the future short rate. This approach of representing the information on the market participants’ consensus in the form of implied model parameters and using these implied parameters for forecasting purposes resembles the approach of representing the market expectation of the underlying asset volatility reflected by stock option prices in the form of implied volatility, and using it to forecast the realized volatility. We illustrate the implementation of this method using historical US STRIPS prices and effective Federal Funds rate.
DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite
Authors: Nation Haley L. , Nicoleau Marvin , Kinsman Brian J. , Browning Kirsteen N. , Stocker Sean D.
Published: March 2016

The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis through its ability to integrate neurohumoral signals and subsequently alter behavior, neuroendocrine function, and autonomic outflow. The purpose of the present study was to evaluate whether selective activation of SFO neurons using virally mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice (12–15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO) produced dose-dependent increases in water intake of mice with DREADD expression in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of CNO significantly increased the number of Fos-positive nuclei in the SFO of mice with robust DREADD expression. Furthermore, in vivo single-unit recordings demonstrate that CNO significantly increases the discharge frequency of both ANG II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that bath application of CNO produces a significant membrane depolarization and increase in action potential frequency. In a final set of experiments, chronic administration of CNO approximately doubled 24-h water intake without an effect on salt appetite. These findings demonstrate that DREADD-induced activation of SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or chronically manipulate neuronal circuits influencing body fluid homeostasis.
Cytokine Interactions with Epithelium
Authors: Barrett Kim E
Published: March 2016

Cytokines are a family of proteins that serve as intracellular messengers within the immune system and as growth factors for several cell types. Recent studies indicate that intestinal inflammation is accompanied by increases in a wide variety of cytokines and growth factors. Current knowledge in the area of cytokine‐epithelial interactions, with particular reference to the involvement of such interactions in intestinal inflammation, is reviewed. Topics include epithelial functions subject to modulation by cytokines; effects of cytokines on epithelial damage, restitution and proliferation; effects of cytokines on the ability of the epithelium to express immune accessory and adhesion molecules; and effects of cytokines on the production of inflammatory mediators by the epithelium.
Treatment of Chronic Hepatitis B with Interferon: Long Term Follow‐Up
Authors: Villeneuve Jean-Pierre , Willems Bernard
Published: March 2016

The aim of treatment of chronic hepatitis B with interferon is to induce a transition from the replicative phase of the disease to a nonreplicative state, with loss of hepatitis B virus (HBV)‐DNA, seroconversion from hepatitis B e antigen (HBeAg)‐positive to anti‐HBe antibody‐positive, and normalization of liver enzymes. The authors’ experience in 22 patients with chronic hepatitis B treated with recombinant human interferon alpha‐2b (5 MU/m2 subcutaneously three times/week for 16 weeks) is reported. Before treatment all patients had been positive for hepatitis B surface antigen (HBsAg) and HBeAg for at least six months, had abnormal serum aminotransferases, had no evidence of hepatitis D or human immunodeficiency virus (HIV) infection and had compensated liver disease. Eleven of 22 patients (50%) responded to treatment with loss of HBeAg and appearance of anti‐HBe antibodies, and normalization of serum aminotransferases within six months of interferon cessation. Patients were followed for 3.4±1.2 years after treatment. Ten of 11 responders remained negative for HBeAg and HBV‐DNA; one patient relapsed and responded to a second course of interferon with loss of HBeAg and HBV‐DNA. Seven of the 11 nonresponders underwent spontaneous (n=5) or retreatment‐induced (n=2) seroconversion from HBeAg to anti‐HBe and loss of HBV‐DNA during follow‐up. The other four nonresponders remained positive for HBeAg and HBV‐DNA; three of the four progressed to decompensated liver disease. It is concluded that interferon is an effective treatment of chronic hepatitis B in 50% of patients with features similar to those used as selection criteria in the present study. These criteria probably also identify patients who have a high likelihood of spontaneous HBeAg to anti‐HBe seroconversion, and it is possible that the benefit of interferon is its acceleration of this seroconversion.
Serum Immunoglobulin A (IgA) Level Is a Potential Biomarker Indicating Cirrhosis during Chronic Hepatitis B Infection
Authors: Lin Sha , Sun QinQin , Mao WeiLin , Chen Yu
Published: March 2016

Background. Serum immunoglobulins (Igs) are frequently elevated in patients with chronic liver disease, but currently there is a lack of sufficient data on serum Igs in patients with chronic hepatitis B virus (CHB) infection. This study aimed to evaluate serum IgA, IgG, and IgM levels in patients with HBV-related cirrhosis and to analyze, if altered, immunoglobulin levels that were associated with cirrhosis progress.Methods. A cohort of 174 CHB patients including 104 with cirrhosis (32 decompensated and 72 compensated) and 70 without cirrhosis and 55 healthy controls were enrolled. Serum immunoglobulin levels and biochemical and virological parameters were determined in the enrollment blood samples.Results. Serum IgA levels were significantly increased in cirrhosis group compared with noncirrhosis group and healthy controls (allP<0.001). Furthermore, serum IgA concentrations in decompensated cirrhosis patients were significantly higher than that of compensated patients (P=0.002). Multivariate analysis suggested that serum IgA, platelets, and albumin were independent predictors for cirrhosis (allP<0.001).Conclusions. Elevated IgA levels may function as an independent factor indicating cirrhosis, and there appears to be a strong association between increasing serum IgA level and disease progressing in patients with chronic HBV infection.