bluuebunny/crossref_metadata_2025 huggingface dataset:
Prior knowledge, transformative learning and performance
Authors: Chih Wen-Hai , Huang Ling-Chu , Yang Tsung-Ju
Published: January 2016

Purpose

– The purpose of this paper is to explore the prior knowledge perspective on e-business environments to maintain expertise by firms. The perspectives indicate the crucial of e-service innovation and emphasize the transformative learning in the model.

Design/methodology/approach

– The model proposed in this study examines the relationships among customer empowerment, normative pressure, innovativeness, transformative learning, and performance. This study presents empirical results from benchmark services in e-markets of Taiwan. There were 225 valid samples to test the proposed model with SEM.

Findings

– Customer empowerment has significant and positive effects on innovativeness and transformative learning, respectively. Normative pressure has significant and positive effects on innovativeness and transformative learning, respectively. Innovativeness has significant and positive effects on transformative learning. Transformative learning has significant and positive effects on financial, customer, and business performance, respectively. In addition, innovativeness mediates the effects of customer empowerment and normative pressure on transformative learning.

Research limitations/implications

– This study finds that transformative learning is a crucial role on customer performance. Firms should emphasize on transformative learning of prior market and technological knowledge to achieve customer performance.

Originality/value

– Customer empowerment is the technological knowledge innovation of e-business environments. However, normative pressure has to implement the market knowledge orientation on e-business environments. Besides, transformative learning has the largest effect on customer performance.
The case study in telecommunications policy research
Authors: Sutherland Ewan
Published: January 2016

Purpose

The purpose of this paper is to examine the use of case studies in telecommunications policy research (TPR) and to compare and contrast usage with management, management information systems (MIS) and policy analysis.

Design/methodology/approach

This paper conducts a comparative analysis that examines the methodologies used to design and select case studies and the various theories used in their analysis.

Findings

The most sophisticated use of case studies is in management information systems (MIS), distinguishing critical realism, interpretivism and positivism to build theories. In policy analysis and TPR, theories are used to explain case studies, which are chosen as interesting sets of phenomena, rather than as means to extend, falsify or verify theories.

Research limitations/implications

Researchers in telecommunications policy should consider the approaches taken in MIS to determine whether they might improve their rigor. There is also scope for meta-analyses of the existing pool of case studies.

Originality/value

This appears to be the first article examining the use of case studies in TPR.
Children’s section of the Jaffna Public Library: user satisfaction survey
Authors: Chandrasekar Kalpana , Sivathaasan Nadarajah
Published: January 2016

Purpose

– This survey research aims to investigate the level of satisfaction among children (up to 14 years) with regard to facilities and services available at the children’s section of the Jaffna Public Library (JPL, Sri Lanka).

Design/methodology/approach

– A structured questionnaire was distributed among randomly selected members of the children’s section, JPL. Data collected via the structured questionnaire were analysed using SPSS 22.0. In addition to the descriptive analysis, independent samples t-test and f-test were conducted to observe the influence of personal variables on different facets of user satisfaction.

Findings

– The response rate was 67 per cent. Descriptive analysis showed that the prime purpose of visiting the children’s section (JPL) is reading books and other materials. With regard to frequency of visit, 86 per cent of the respondents visit the library three to four times in a week or at least once a week. Results of the f-test indicated that there is no significant difference among different age groups for overall satisfaction of children’s section facilities and services. Results of the t-test revealed that female children are more satisfied with the library environment compared to males. Further, the level of satisfaction with shelf arrangement, library environment and children’s programmes differed significantly between children studying in the bilingual and the Tamil mediums.

Originality/value

– This study reports the empirical findings of the user survey carried out at the children’s section of the JPL.
A comparative study of information literacy provision at university libraries in South Africa and the United Arab Emirates
Authors: Moyo Mathew , Mavodza Judith
Published: January 2016

Purpose

– The purpose of this paper is to establish and compare the provision of information literacy (IL) skills to university students both at undergraduate and graduate levels in South Africa (SA) and the United Arab Emirates (UAE). This could in turn inform the development of appropriate/suitable IL programmes to support teaching and learning.

Design/methodology/approach

– A review of available scholarly papers is performed for information collection.

Findings

– The findings can identify variations in IL provision within and across disciplines, deficiencies in local current and ongoing research.

Research limitations/implications

– It must be noted that this is a review and conclusions from it are expected to reveal areas that require more in-depth study.

Practical implications

– The study’s contribution to the field of IL lies in its revelation of what is understood by IL provision and how the ACRL standards are used to guide practice in the two different regions of the world.

Originality/value

– The study is the first of its kind which compares IL practices at university libraries in SA and the UAE. It will assist policymakers and librarians in the development of appropriate IL programmes in support of teaching and learning.
Primary records: what future?
Authors: Kargbo John Abdul
Published: January 2016

Purpose

– This paper aims to, invariably, critically look at primary records, their origins, categorization, uses and what the future holds for them, amid changing times. From the cradle of civilization, people have been using varied ways to record, store and distribute information. Years back, people kept their records on such materials as wax, papyrus, leather, clay, parchment, paper and wood. But recent technological developments have brought about different formats which in turn have influenced the choice of materials and methods used to write and circulate information.

Design/methodology/approach

– This is a viewpoint paper on primary documents in library and information service institutions. The paper critically looks at the different types of primary documents, how they are collected, the challenges involved and their future amid changing technological times. Relevant literature was consulted, including the Internet.

Findings

– The findings are that the future of primary documents will remain bleak if librarians, curators, records managers and archivists do not give serious thought to primary documents regardless of the fact that they are germane in library and information science.

Originality/value

– This is a viewpoint paper on primary documents. Relevant information was drawn from varied readings in library and information service institutions as well as from the Internet.
Xerostomia among older home care clients
Authors: Viljakainen Sari , Nykänen Irma , Ahonen Riitta , Komulainen Kaija , Suominen Anna Liisa , Hartikainen Sirpa , Tiihonen Miia
Published: January 2016

Objectives

The purpose of this study was to examine drug use and other factors associated with xerostomia in home care clients aged 75 years or older.

Methods

The study sample included 270 home care clients aged ≥75 years living in Eastern and Central Finland. The home care clients underwent in‐home interviews carried out by trained home care nurses, nutritionists, dental hygienists and pharmacists. The collected data contained information on sociodemographic factors, health and oral health status, drug use, depressive symptoms (GDS‐15), cognitive functioning (MMSE), functional ability (Barthel Index, IADL) and nutrition (MNA). The primary outcome was xerostomia status (never, occasionally or continuously).

Results

Among the home care clients, 56% (n = 150) suffered from xerostomia. Persons with continuous xerostomia used more drugs and had more depressive symptoms and a higher number of comorbidities than other home care clients. In multivariate analyses, excessive polypharmacy (OR = 1.83, 95% Cl 1.08−3.10) and depressive symptoms (OR = 1.12, 95% Cl 1.03−1.22) were associated with xerostomia.

Conclusions

Xerostomia is a common problem among old home care clients. Excessive polypharmacy, use of particular drug groups and depressive symptoms were associated with xerostomia. The findings support the importance of a multidisciplinary approach in the care of older home care clients.
Interleukin‐6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus
Authors: Birner Peter , Heider Susanne , Petzelbauer Peter , Wolf Peter , Kornauth Christoph , Kuroll Madeleine , Merkel Olaf , Steiner Günter , Kishimoto Tadamitsu , Rose‐John Stefan , Soleiman Afschin , Moriggl Richard , Kenner Lukas
Published: January 2016

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by antinuclear autoantibodies (ANA) and immunocomplexes, commonly affecting kidneys, skin, heart, lung or even the brain. We have shown that JunBΔep mice develop a SLE phenotype linked to increased epidermal Interleukin (IL)‐6 secretion. Blocking of IL‐6 receptor alpha (IL‐6Rα) is considered as therapeutic strategy for the treatment of SLE. JunBΔep and wild‐type mice were treated for short (5 weeks) or long term (21 weeks) with the IL‐6Rα‐blocking antibody MR16‐1. Skin and kidney of mice were investigated by histology and immunofluorescence, and in addition, kidneys were analysed by electron microscopy. Furthermore, soluble IL‐6R (sIL‐6R), antihistone and antinucleosome antibodies levels were measured and associated with disease parameters. Treatment with MR16‐1 resulted in significant improvement of SLE‐like skin lesions in JunBΔep mice, compared to untreated mice. The sIL‐6R amount upon long‐term treatment with MR16‐1 was significantly higher in JunBΔep versus untreated JunBΔep (P = 0.034) or wild‐type mice (P = 0.034). MR16‐1 treatment over these time spans did not significantly improve kidney pathology of immunoglobulin deposits causing impaired function. Significantly higher antihistone (P = 0.028) and antinucleosome antibody levels (P = 0.028) were measured in MR16‐1‐treated JunBΔep mice after treatment compared to levels before therapy. In conclusion, blockade of IL‐6Rα improves skin lesions in a murine SLE model, but does not have a beneficial effect on autoimmune‐mediated kidney pathology. Inhibition of IL‐6R signalling might be helpful in lupus cases with predominant skin involvement, but combinatorial treatment might be required to restrain autoantibodies.
Anatomy, morphology and evolution of the patella in squamate lizards and tuatara (Sphenodon punctatus)
Authors: Regnault Sophie , Jones Marc E. H. , Pitsillides Andrew A. , Hutchinson John R.
Published: January 2016

The patella (kneecap) is the largest and best‐known of the sesamoid bones, postulated to confer biomechanical advantages including increasing joint leverage and reinforcing the tendon against compression. It has evolved several times independently in amniotes, but despite apparently widespread occurrence in lizards, the patella remains poorly characterised in this group and is, as yet, completely undescribed in their nearest extant relative Sphenodon (Rhynchocephalia). Through radiography, osteological and fossil studies we examined patellar presence in diverse lizard and lepidosauromorph taxa, and using computed tomography, dissection and histology we investigated in greater depth the anatomy and morphology of the patella in 16 lizard species and 19 Sphenodon specimens. We have found the first unambiguous evidence of a mineralised patella in Sphenodon, which appears similar to the patella of lizards and shares several gross and microscopic anatomical features. Although there may be a common mature morphology, the squamate patella exhibits a great deal of variability in development (whether from a cartilage anlage or not, and in the number of mineralised centres) and composition (bone, mineralised cartilage or fibrotendinous tissue). Unlike in mammals and birds, the patella in certain lizards and Sphenodon appears to be a polymorphic trait. We have also explored the evolution of the patella through ancestral state reconstruction, finding that the patella is ancestral for lizards and possibly Lepidosauria as a whole. Clear evidence of the patella in rhynchocephalian or stem lepidosaurian fossil taxa would clarify the evolutionary origin(s) of the patella, but due to the small size of this bone and the opportunity for degradation or loss we could not definitively conclude presence or absence in the fossils examined. The pattern of evolution in lepidosaurs is unclear but our data suggest that the emergence of this sesamoid may be related to the evolution of secondary ossification centres and/or changes in knee joint conformation, where enhancement of extensor muscle leverage would be more beneficial.
Legitimizing Family Management: The Role of Adolescents' Understandings of Risk
Authors: Ispa‐Landa Simone
Published: January 2016

Few studies use the kinds of rich qualitative data that permit the analyst to probe for the numerous ways that contextual demands could explain adolescents' interpretations of the socialization processes within their families. Using inductive techniques, the author analyzed Black adolescents' (N = 64) interpretations of their parents' expectations and rules. Several findings emerged. First, agreeing with parents' assessments of risk was critical to participants' acceptance of family management. Second, participants legitimized their parents' practices as helping them avoid the risks of getting in trouble with the law, acquiring a disreputable identity, and failing to ascend the class ladder. Third, boys and girls legitimized different expectations and rules because they experienced and assessed risks in gender‐specific ways. The author argues that adolescents bring an understanding of risk to bear on their interpretations of family life and uses these findings to develop a grounded concept of legitimizing parents' controlling practices.
Repeated exposure to whole cigarette smoke promotes primary human gingival epithelial cell growth and modulates keratin expression
Authors: Alharbi I. A. , Rouabhia M.
Published: January 2016

Background and Objective

The gingiva is the first oral tissue directly exposed to cigarette smoke (CS). Exposure to CS compromises the structure and function of gingival tissue. Damaging or altering the gingival epithelium leads to a compromised protective barrier of the periodontium, resulting in several diseases. The aim of this study was to assess the effect of repeated exposure to CS on gingival epithelial cell growth and on expression of apoptotic protein and keratin.

Material and Methods

Primary human gingival epithelial cells were seeded on a collagen scaffold for 5 d to allow growth and stratification. The cells were then exposed for 5 min to whole CS for 3, 6 and 9 d. At the end of each exposure period, cell proliferation [using (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) (MTT) and 5‐bromo‐2′‐deoxyuridine (BrdU) assays], gene expression [by quantitative reverse transcription polymerase chain reaction (qRT‐PCR)] and protein production (by western blot analysis) were investigated.

Results

Higher metabolic activity was found in the CS‐exposed cells than in the nonexposed cells, specifically after 3 and 6 d of exposure to CS. At 9 d there was no significant difference between CS‐exposed and nonexposed cells. Metabolic activity was supported by the BrdU cell‐proliferation analyses, which showed increased cell growth at 3 d compared with the control. However, at 6 and 9 d, cell proliferation in the CS‐exposed culture was comparable to that in the nonexposed culture. Interestingly, the Bax/Bcl‐2 protein ratios decreased with increased CS exposure, suggesting cell resistance. Moreover, protein analyses showed that CS decreased expression of keratin(K) 5 at 3, 6 and 9 d, and increased expression of K14 at 6 and 9 d. Finally, mRNA analyses showed significant decreases of K1, K6, K10 and K16 in CS‐exposed cultures, correlating, at times, with a decrease of protein production.

Conclusion

CS was shown to increase epithelial cell proliferation, which may involve cell resistance to apoptosis. This is supported by the modulation of expression of different keratin genes and proteins. Altogether, these data may explain the hyperplasia reported in gingival tissue, as well as periodontal disease, in smokers.
Breed Distribution and Clinical Characteristics of B Cell Chronic Lymphocytic Leukemia in Dogs
Authors: Bromberek J.L. , Rout E.D. , Agnew M.R. , Yoshimoto J. , Morley P.S. , Avery A.C.
Published: January 2016

Background

B‐cell chronic lymphocytic leukemia (B‐CLL) is the most common hematopoietic malignancy in humans in the developed world and the primary risk factor is genetic. Dogs also develop B‐CLL, but there is no systematic description of the disease in dogs. Understanding the epidemiology of B‐CLL in dogs may help practitioners recognize the disease and position the dog as a model for future genetic studies.

Objectives

To describe B‐CLL presentation in dogs, its clinicopathologic findings, and breed predisposition.

Animals

Four hundred and ninety‐one dogs with B‐CLL and 5,673 control dogs with suspicion of a lymphoproliferative disorder (LPD).

Methods

Retrospective cross‐sectional study of dogs for which samples were submitted to the Colorado State University Clinical Immunology Laboratory for immunophenotyping between 2010 and 2014. To assess breed predilection, dogs with B‐CLL were compared to those with suspicion of other LPDs using logistic regression.

Results

The median age was 11 years with no sex predilection. Half of the dogs presented with peripheral lymphadenopathy or splenomegaly and 26% had anemia. Eleven small‐breed dogs had significantly increased odds of B‐CLL. In addition, English Bulldogs had an increased risk and a unique presentation: these dogs were diagnosed at a median of 6 years and expressed lower class II MHC and CD25.

Conclusions

B‐cell chronic lymphocytic leukemia is overrepresented in small‐breed dogs. Future genetic studies of these breeds may identify genetic risk factors. The unique presentation of English Bulldogs provides evidence of multiple forms of this disease. Additional studies are necessary to determine whether presenting signs are associated with survival.
Gestational Age, Birthweight for Gestational Age, and Childhood Hospitalisations for Asthma and Other Wheezing Disorders
Authors: Leung June Y. Y. , Lam Hugh S. , Leung Gabriel M. , Schooling C. Mary
Published: January 2016

Background

Preterm birth, early term birth, and low birthweight are associated with childhood wheezing disorders in developed Western settings, but observed associations could be confounded by socio‐economic position. This study aims to clarify such associations in a developed non‐Western setting with a different confounding structure.

Methods

Using Cox regression, we examined the adjusted associations of gestational age and birthweight for gestational age with time to first public hospital admission for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version Clinical Modification 466, 490, and 493) from 9 days to 12 years in a population‐representative birth cohort of 8327 Chinese children in Hong Kong, a developed setting with less clear social patterning of prematurity or birthweight. Analyses were adjusted for infant and parental characteristics and socio‐economic position.

Results

Children born late preterm (34 to <37 weeks) had higher risk of hospitalisation for asthma and other wheezing disorders [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.48, 2.67] than children born full term (39 to <41 weeks). Early term births (37 to <39 weeks) had HR 1.01 (95% CI 0.84, 1.22), late term births (41 to <42 weeks) had HR 0.77 (95% 0.59, 1.01), and post‐term births (≥42 weeks) had HR 0.56 (95% CI 0.32, 0.98). Large for gestational age was associated with lower risk of hospitalisation (HR 0.76, 95% CI 0.57, 0.99).

Conclusion

The association of preterm birth with childhood wheezing could be biologically mediated. We cannot rule out an association for early term births.
Understanding the Lives of Mothers after Incarceration: Moving Beyond Socially Constructed Definitions of Motherhood
Authors: Garcia Janet
Published: January 2016

In the wake of mass incarceration, an increasing number of women are going through the penal system. A fair number of these women are mothers, yet the intersection of motherhood and prison may contradict conceptions of femininity and challenge traditional views of appropriate mothering. The contradiction between notions of criminality and femininity contributes to stigmatized perceptions of formerly incarcerated mothers, which drastically shapes their ability to reintegrate into society post‐incarceration. While reentry efforts tackle gender differences through the implementation of gender‐responsive programs that cater to women's needs, failure to adequately account for unique maternal experiences may hinder attempts to address obstacles faced by mothers in particular, such as regaining child custody and paying for day care. This article argues for special attention to the post‐incarceration experiences of mothers without imposing socially constructed definitions of motherhood like having custody and living with children, which may not coincide with the realities mothers face after imprisonment. Ideas are also discussed for the inclusive consideration of formerly incarcerated mothers and their post‐incarceration experiences.
An Examination of the True Reliability of Lower Limb Stiffness Measures During Overground Hopping
Authors: Diggin David , Anderson Ross , Harrison Andrew J.
Published: January 2016

Evidence suggests reports describing the reliability of leg-spring (kleg) and joint stiffness (kjoint) measures are contaminated by artifacts originating from digital filtering procedures. In addition, the intraday reliability of kleg and kjoint requires investigation. This study examined the effects of experimental procedures on the inter- and intraday reliability of kleg and kjoint. Thirty-two participants completed 2 trials of single-legged hopping at 1.5, 2.2, and 3.0 Hz at the same time of day across 3 days. On the final test day a fourth experimental bout took place 6 hours before or after participants’ typical testing time. Kinematic and kinetic data were collected throughout. Stiffness was calculated using models of kleg and kjoint. Classifications of measurement agreement were established using thresholds for absolute and relative reliability statistics. Results illustrated that kleg and kankle exhibited strong agreement. In contrast, kknee and khip demonstrated weak-to-moderate consistency. Results suggest limits in kjoint reliability persist despite employment of appropriate filtering procedures. Furthermore, diurnal fluctuations in lower-limb muscle-tendon stiffness exhibit little effect on intraday reliability. The present findings support the existence of kleg as an attractor state during hopping, achieved through fluctuations in kjoint variables. Limits to kjoint reliability appear to represent biological function rather than measurement artifact.
A race to explain Brazil's spike in birth defects
Authors: Vogel Gretchen
Published: January 2016

Evidence points toward the fast-spreading Zika virus as the cause of microcephaly.
Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition
Authors: Basu Jayeeta , Zaremba Jeffrey D. , Cheung Stephanie K. , Hitti Frederick L. , Zemelman Boris V. , Losonczy Attila , Siegelbaum Steven A.
Published: January 2016

Fine-tuned information flow in the brain

In addition to providing well-characterized excitatory inputs, the entorhinal cortex also sends long-range inhibitory projections to the hippocampus. Basu
et al.
described this input in detail and characterized its role for learning and memory. Multimodal sensory stimuli activate long-range inhibitory input in vivo. This input enables precisely timed information transfer within the cortico-hippocampal circuit. In this way, long-range inhibitory projections play an important role in providing specificity of fear conditioning, and thus help prevent overgeneralization.

Science
, this issue p.
10.1126/science.aaa5694
The 5300-year-old
Helicobacter pylori
genome of the Iceman
Authors: Maixner Frank , Krause-Kyora Ben , Turaev Dmitrij , Herbig Alexander , Hoopmann Michael R. , Hallows Janice L. , Kusebauch Ulrike , Vigl Eduard Egarter , Malfertheiner Peter , Megraud Francis , O’Sullivan Niall , Cipollini Giovanna , Coia Valentina , Samadelli Marco , Engstrand Lars , Linz Bodo , Moritz Robert L. , Grimm Rudolf , Krause Johannes , Nebel Almut , Moodley Yoshan , Rattei Thomas , Zink Albert
Published: January 2016

Stomach ache for a European mummy

Five thousand years ago in the European Alps, a man was shot by an arrow, then clubbed to death. His body was subsequently mummified by ice until glacier retreat exhumed him in 1991. Subsequently, this ancient corpse has provided a trove of intriguing information about copper-age Europeans. Now, Maixner
et al.
have identified the human pathogen
Helicobacter pylori
within the mummy's stomach contents. The strain the “Iceman” hosted appears to most closely resemble pathogenic Asian strains found today in Central and Southern Asia.

Science
, this issue p.
162
The structure of the β-barrel assembly machinery complex
Authors: Bakelar Jeremy , Buchanan Susan K. , Noinaj Nicholas
Published: January 2016

Going in with a BAM

Integral membrane proteins in bacterial outer membranes play roles in nutrient import and infectivity. These proteins are folded into a barrel shape composed of β-strands and inserted into the outer membrane by the β-barrel assembly machinery (BAM) complex. Bakelar
et al.
determined the crystal structure of a four-component BAM subcomplex. The structure of a central β barrel in BAM changes in the presence of the accessory components to create a lateral opening that may be involved in how BAM inserts proteins into the outer membrane.

Science
, this issue p.
180
The supercollider that wasn't
Tunnel Visions The Rise and Fall of the Superconducting Super Collider
Michael Riordan, Lillian Hoddeson, Adrienne W. Kolb
University of Chicago Press, 2015. 462 pp.
Authors: Mervis Jeffrey
Published: January 2016

An ambitious history of the SSC falls short on lessons for future megascience projects
Detection of Atypical H-Type Bovine Spongiform Encephalopathy and Discrimination of Bovine Prion Strains by Real-Time Quaking-Induced Conversion
Authors: Masujin Kentaro , Orrú Christina D. , Miyazawa Kohtaro , Groveman Bradley R. , Raymond Lynne D. , Hughson Andrew G. , Caughey Byron
Published: January 2016

Prion diseases of cattle include the classical bovine spongiform encephalopathy (C-BSE) and the atypical H-type BSE (H-BSE) and L-type BSE (L-BSE) strains. Although the C- and L-BSE strains can be detected and discriminated by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays, no such test has yet been described for the detection of H-BSE or the discrimination of each of the major bovine prion strains. Here, we demonstrate an RT-QuIC assay for H-BSE that can detect as little as 10−9dilutions of brain tissue and neat cerebrospinal fluid samples from clinically affected cattle. Moreover, comparisons of the reactivities with different recombinant prion protein substrates and/or immunoblot band profiles of proteinase K-treated RT-QuIC reaction products indicated that H-, L-, and C-BSE have distinctive prion seeding activities and can be discriminated by RT-QuIC on this basis.
Comparison of Performance Characteristics of Aspergillus PCR in Testing a Range of Blood-Based Samples in Accordance with International Methodological Recommendations
Authors: Springer Jan , White P. Lewis , Hamilton Shanna , Michel Denise , Barnes Rosemary A. , Einsele Hermann , Löffler Juergen
Published: January 2016

Standardized methodologies for the molecular detection of invasive aspergillosis (IA) have been established by the European
Aspergillus
PCR Initiative for the testing of whole blood, serum, and plasma. While some comparison of the performance of
Aspergillus
PCR when testing these different sample types has been performed, no single study has evaluated all three using the recommended protocols. Standardized
Aspergillus
PCR was performed on 423 whole-blood pellets (WBP), 583 plasma samples, and 419 serum samples obtained from hematology patients according to the recommendations. This analysis formed a bicenter retrospective anonymous case-control study, with diagnosis according to the revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (11 probable cases and 36 controls). Values for clinical performance using individual and combined samples were calculated. For all samples, PCR positivity was significantly associated with cases of IA (for plasma,
P
= 0.0019; for serum,
P
= 0.0049; and for WBP,
P
= 0.0089). Plasma PCR generated the highest sensitivity (91%); the sensitivities for serum and WBP PCR were 80% and 55%, respectively. The highest specificity was achieved when testing WBP (96%), which was significantly superior to the specificities achieved when testing serum (69%,
P
= 0.0238) and plasma (53%,
P
= 0.0002). No cases were PCR negative in all specimen types, and no controls were PCR positive in all specimens. This study confirms that
Aspergillus
PCR testing of plasma provides robust performance while utilizing commercial automated DNA extraction processes. Combining PCR testing of different blood fractions allows IA to be both confidently diagnosed and excluded. A requirement for multiple PCR-positive plasma samples provides similar diagnostic utility and is technically less demanding. Time to diagnosis may be enhanced by testing multiple contemporaneously obtained sample types.
Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B
Authors: Kong Lingbao , Fujimoto Akira , Nakamura Mariko , Aoyagi Haruyo , Matsuda Mami , Watashi Koichi , Suzuki Ryosuke , Arita Minetaro , Yamagoe Satoshi , Dohmae Naoshi , Suzuki Takehiro , Sakamaki Yuriko , Ichinose Shizuko , Suzuki Tetsuro , Wakita Takaji , Aizaki Hideki
Published: January 2016

It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection
in vitro
and
in vivo
. Our findings provide new insights into HCV host cofactors.

IMPORTANCE
The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication compartment is not understood. We screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis, followed by screening with small interfering RNA. We identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. PREB is induced by HCV infection and recruited into the replication complex by interaction with NS4B. Recruited PREB promotes HCV RNA replication by participating in the formation of the membranous HCV replication compartment. To our knowledge, the effect of NS4B-binding protein on the formation of the membranous HCV replication compartment is newly described in this report. Our findings are expected to provide new insights into HCV host cofactors.
The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses
Authors: Pécheur Eve-Isabelle , Borisevich Viktoriya , Halfmann Peter , Morrey John D. , Smee Donald F. , Prichard Mark , Mire Chad E. , Kawaoka Yoshihiro , Geisbert Thomas W. , Polyak Stephen J.
Published: January 2016

Arbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibits
in vitro
hepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppresses
in vitro
infection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality.

IMPORTANCE
There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus, Tacaribe arenavirus, and HHV-8, and we propose ARB as a broad-spectrum antiviral drug that may be useful against hemorrhagic viruses.
Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication
In Vivo
Authors: Bergvall Monika , Gagnon David , Titolo Steve , Lehoux Michaël , D'Abramo Claudia M. , Melendy Thomas , Archambault Jacques
Published: January 2016

The papillomavirus (PV) E1 helicase contains a conserved C-terminal domain (CTD), located next to its ATP-binding site, whose function
in vivo
is still poorly understood. The CTD is comprised of an alpha helix followed by an acidic region (AR) and a C-terminal extension termed the C-tail. Recent biochemical studies on bovine papillomavirus 1 (BPV1) E1 showed that the AR and C-tail regulate the oligomerization of the protein into a double hexamer at the origin. In this study, we assessed the importance of the CTD of human papillomavirus 11 (HPV11) E1
in vivo
, using a cell-based DNA replication assay. Our results indicate that combined deletion of the AR and C-tail drastically reduces DNA replication, by 85%, and that further truncation into the alpha-helical region compromises the structural integrity of the E1 helicase domain and its interaction with E2. Surprisingly, removal of the C-tail alone or mutation of highly conserved residues within the domain still allows significant levels of DNA replication (55%). This is in contrast to the absolute requirement for the C-tail reported for BPV1 E1
in vitro
and confirmed here
in vivo
. Characterization of chimeric proteins in which the AR and C-tail from HPV11 E1 were replaced by those of BPV1 indicated that while the function of the AR is transferable, that of the C-tail is not. Collectively, these findings define the contribution of the three CTD subdomains to the DNA replication activity of E1
in vivo
and suggest that the function of the C-tail has evolved in a PV type-specific manner.

IMPORTANCE
While much is known about hexameric DNA helicases from superfamily 3, the papillomavirus E1 helicase contains a unique C-terminal domain (CTD) adjacent to its ATP-binding site. We show here that this CTD is important for the DNA replication activity of HPV11 E1
in vivo
and that it can be divided into three functional subdomains that roughly correspond to the three conserved regions of the CTD: an alpha helix, needed for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1
in vitro
. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner.
A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice
Authors: Martín V. , Pascual E. , Avia M. , Rangel G. , de Molina A. , Alejo A. , Sevilla N.
Published: January 2016

Ovine interferon tau (IFN-τ) is a unique type I interferon with low toxicity and a broad host rangein vivo. We report the generation of a nonreplicative recombinant adenovirus expressing biologically active IFN-τ. Using the B6.A2G-Mx1 mouse model, we showed that single-dose intranasal administration of recombinant Ad5-IFN-τ can effectively prevent lethality and disease induced by highly virulent hv-PR8 influenza virus by activating the interferon response and preventing viral replication.
Changes in diabetes care indicators: findings from German National Health Interview and Examination Surveys 1997–1999 and 2008–2011
Authors: Du Yong , Heidemann Christin , Schaffrath Rosario Angelika , Buttery Amanda , Paprott Rebecca , Neuhauser Hannelore , Riedel Thea , Icks Andrea , Scheidt-Nave Christa
Published: January 2016

Objectives

To investigate changes in type 2 diabetes care indicators over time in Germany.

Methods

Adults aged 45–79 years with type 2 diabetes were identified from two national health examination surveys conducted in 1997–1999 (GNHIES98, n=333) and in 2008–2011 (DEGS1, n=526). We examined diabetes care indicators including treatment and preventive targets (glycemic control, blood pressure (BP), total cholesterol (TC), smoking, weight reduction, sports activity), self-management and care process measures (glucose self-monitoring, holding a diabetes passport, annual foot and eye examination; statin use), and the presence of diabetes-specific complications (diabetic nephropathy, retinopathy, neuropathy, diabetic foot, amputations) and comorbid cardiovascular disease (CVD) or chronic kidney disease (CKD). We calculated proportions of persons meeting these care indicators by survey and examined unadjusted and adjusted changes between surveys.

Results

Significant improvement (GNHIES98 vs DEGS1) over time was observed for glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) (32.4% vs 65.4%), BP <130/80 mm Hg (32.0% vs 47.2%), TC <190 mg/dL (13.5% vs 41.9%), statin use (11.7% vs 35.9%), eye (51.1% vs 78.4%) and foot (48.0% vs 61.4%) examination within the past 12 months, diabetes-specific complications (29.7% vs 21.8%), and CVD (44.5% vs 37.1%). Blood glucose self-monitoring significantly increased (37.4% vs 62.8%), while holding a diabetes passport did not change. Current smoking did not change and obesity rose, although sports activity significantly increased over time. Proportions of adults achieving combination goals of HbA1c, BP, TC, and smoking cessation were low in both surveys in spite of significant improvement.

Conclusions

In Germany, the quality of diabetes care improved over time. There is much room for improvement, in particular regarding preventive goals and diabetes self-management.
Effects of economic crises on population health outcomes in Latin America, 1981–2010: an ecological study
Authors: Williams Callum , Gilbert Barnabas James , Zeltner Thomas , Watkins Johnathan , Atun Rifat , Maruthappu Mahiben
Published: January 2016

Objectives

The relative health effects of changes in unemployment, inflation and gross domestic product (GDP) per capita on population health have not been assessed. We aimed to determine the effect of changes in these economic measures on mortality metrics across Latin America.

Design

Ecological study.

Setting

Latin America (21 countries), 1981–2010.

Outcome measures

Uses multivariate regression analysis to assess the effects of changes in unemployment, inflation and GDP per capita on 5 mortality indicators across 21 countries in Latin America, 1981–2010. Country-specific differences in healthcare infrastructure, population structure and population size were controlled for.

Results

Between 1981 and 2010, a 1% rise in unemployment was associated with statistically significant deteriorations (p<0.05) in 5 population health outcomes, with largest deteriorations in 1–5 years of age and male adult mortality rates (1.14 and 0.53 rises per 1000 deaths respectively). A 1% rise in inflation rate was associated with significant deteriorations (p<0.05) in 4 population health outcomes, with the largest deterioration in male adult mortality rate (0.0033 rise per 1000 deaths). Lag analysis showed that 5 years after rises in unemployment and inflation, significant deteriorations (p<0.05) occurred in 3 and 5 mortality metrics, respectively. A 1% rise in GDP per capita was associated with no significant deteriorations in population health outcomes either in the short or long term. β coefficient comparisons indicated that the effect of unemployment increases was substantially greater than that of changes in GDP per capita or inflation.

Conclusions

Rises in unemployment and inflation are associated with long-lasting deteriorations in several population health outcomes. Unemployment exerted much larger effects on health than inflation. In contrast, changes in GDP per capita had almost no association with the explored health outcomes. Contrary to neoclassical development economics, policymakers should prioritise amelioration of unemployment if population health outcomes are to be optimised.
Understanding stroke survivors’ and informal carers’ experiences of and need for primary care and community health services—a systematic review of the qualitative literature: protocol
Authors: Aziz N A , Pindus D M , Mullis R , Walter F M , Mant J
Published: January 2016

Introduction

Despite the rising prevalence of stroke, no comprehensive model of postacute stroke care exists. Research on stroke has focused on acute care and early supported discharge, with less attention dedicated to longer term support in the community. Likewise, relatively little research has focused on long-term support for informal carers. This review aims to synthesise and appraise extant qualitative evidence on: (1) long-term healthcare needs of stroke survivors and informal carers, and (2) their experiences of primary care and community health services. The review will inform the development of a primary care model for stroke survivors and informal carers.

Methods and analysis

We will systematically search 4 databases: MEDLINE, EMBASE, PsycINFO and CINAHL for published qualitative evidence on the needs and experiences of stroke survivors and informal carers of postacute care delivered by primary care and community health services. Additional searches of reference lists and citation indices will be conducted. The quality of articles will be assessed by 2 independent reviewers using a Critical Appraisal Skills Programme (CASP) checklist. Disagreements will be resolved through discussion or third party adjudication. Meta-ethnography will be used to synthesise the literature based on first-order, second-order and third-order constructs. We will construct a theoretical model of stroke survivors’ and informal carers’ experiences of primary care and community health services.

Ethics and dissemination

The results of the systematic review will be disseminated via publication in a peer-reviewed journal and presented at a relevant conference. The study does not require ethical approval as no patient identifiable data will be used.