bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with changes in exposure to anticholinergic and sedative medications in elderly hospitalized patients: multicentre longitudinal study
Authors: Dauphinot V. , Faure R. , Bourguignon L. , Goutelle S. , Krolak‐Salmon P. , Mouchoux C.
Published: December 2016

Background and purpose

Elderly patients exposed to drugs with anticholinergic or sedative properties may have an increased risk of adverse events. This study aimed to assess the relationship between patient characteristics and changes of exposure to anticholinergic and sedative medications during their hospital stay.

Methods

A multicentre longitudinal study was set up on hospitalized patients (aged ≥65 years) using at least one drug at admission. The primary outcome was change of exposure to anticholinergic and sedative drugs between admission and discharge. Sociodemographic characteristics of the patients, comorbidities, life habits and information about the hospital stay (origin of admission, reasons for hospitalization) were collected.

Results

The study included 337 patients (mean age, 85.4 years) with an average hospital stay of 30.1 ± 37.5 days. The drug burden index increased during the hospital stay among males (P = 0.03), patients for whom the reason for hospitalization was either a stroke (P = 0.001) or inability to stay in their own home (P = 0.001), and patients with diabetes mellitus (P = 0.009). In the adjusted model, drug burden index increased among patients hospitalized for stroke, inability to stay in their own home or post‐surgery, and for patients with diabetes mellitus or hypertension.

Conclusions

The drug management of elderly patients during hospital stays may increase exposure to anticholinergic and sedative drugs. Although the anticholinergic and sedative properties may be in relation to the therapeutic purpose, they also represent an unexpected risk. Physicians and clinical pharmacists should consider performing optimization of the drug prescriptions for patients at risk.
Plasma D‐dimer levels and ischaemic lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke
Authors: Gon Y. , Sakaguchi M. , Takasugi J. , Kawano T. , Kanki H. , Watanabe A. , Oyama N. , Terasaki Y. , Sasaki T. , Mochizuki H.
Published: December 2016

Background and purpose

Cancer patients with cryptogenic stroke often have high plasma D‐dimer levels and lesions in multiple vascular regions. Hence, if patients with cryptogenic stroke display such characteristics, occult cancer could be predicted. This study aimed to investigate the clinical characteristics of cryptogenic stroke as the first manifestation of occult cancer and to determine whether plasma D‐dimer levels and lesions in multiple vascular regions can predict occult cancer in patients with cryptogenic stroke.

Methods

Between January 2006 and October 2015, data on 1225 patients with acute ischaemic stroke were extracted from the stroke database of Osaka University Hospital. Among them, 184 patients were classified as having cryptogenic stroke, and 120 patients without a diagnosis of cancer at stroke onset were identified. Clinical variables were analyzed between cryptogenic stroke patients with and without occult cancer.

Results

Among 120 cryptogenic stroke patients without a diagnosis of cancer, 12 patients had occult cancer. The body mass index, hemoglobin levels and albumin levels were lower; plasma D‐dimer and high‐sensitivity C‐reactive protein levels were higher; and lesions in multiple vascular regions were more common in patients with than in those without occult cancer. Multiple logistic regression analysis revealed that plasma D‐dimer levels (odds ratio, 3.48; 95% confidence interval, 1.68–8.33; P = 0.002) and lesions in multiple vascular regions (odds ratio, 7.40; 95% confidence interval, 1.70–39.45; P = 0.01) independently predicted occult cancer.

Conclusions

High plasma D‐dimer levels and lesions in multiple vascular regions can be used to predict occult cancer in patients with cryptogenic stroke.
Aggressive pruning strategy for time series retrieval using a multi‐resolution representation based on vector quantization coupled with discrete wavelet transform
Authors: Muhammad Fuad Muhammad Marwan
Published: December 2016

Time series representation methods are widely used to handle time series data by projecting them onto low‐dimensional spaces where queries are processed. Multi‐resolution representation methods speed up the similarity search process by using pre‐computed distances, which are calculated and stored at the indexing stage and then used at the query stage, together with filters in the form of exclusion conditions. In this paper, we present a new multi‐resolution representation method that combines the Haar wavelet‐based multi‐resolution method with vector quantization to maximize the pruning power of the similarity search algorithm. The new method is validated through extensive experiments on different datasets from several time series repositories. The results obtained prove the efficiency of the new method.
Proliferative characteristics of Philadelphia‐negative myeloproliferative neoplasms ‐ clinical implications
Authors: Šefer D. , Bižić‐Radulović S. , Kraguljac‐Kurtović N. , Bogdanović A. , Čokić V. , Miljić P. , Beleslin‐Čokić B. , Knežević V. , Mitrović‐Ajtić O. , Leković D. , Gotić M.
Published: December 2016

Introduction

Philadelphia‐negative myeloproliferative neoplasms (Ph−MPN) are characterized by overproduction of one or more blood cell lines.

Methods

We studied the proliferative characteristics of 91 patients with de novo Ph−MPN. Colony‐forming cells (CFC) and endogenous colonies (EC), from bone marrow (BM) and/or peripheral blood (PB), were analyzed by colony assay based on methylcellulose. The level of circulating CD34+ cells was determined by flow cytometry.

Results

The total number of PB CFC in primary myelofibrosis (PMF) was increased compared to the control sample (P < 0.01) and essential thrombocythemia (ET) (P < 0.05). The highest number of BM and PB EC was observed in polycythemia vera (PV) (P < 0.01). Increased levels of CD34+ cells characterized early‐prefibrotic (57%) and advanced‐fibrotic PMF (90%) as compared to PV (34%) and ET (32%) (P < 0.01). In the whole Ph−MPN group, the total number of PB CFC (P < 0.01), PB EC (P < 0.05), and CD34+ cells (P < 0.01) correlated with the degree of BM fibrosis. Higher levels of circulating CD34+ cells in PMF correlated with the total number of PB EC (P < 0.05) and degree of BM fibrosis (P < 0.01).

Conclusions

Exploration of the PB proliferative characteristics of Ph−MPN on diagnosis may be helpful in revealing early‐prefibrotic PMF. Monitoring the levels of circulating CD34+ cells may provide a sensitive indicator of fibrotic evolution in PV and PMF.
The association between physical activity and mortality among patients undergoing maintenance hemodialysis
Authors: Zhang Lu , Luo Hongmei , Kang Geping , Wang Wenxia , Hu Yalan
Published: December 2016

The aim of this study was to assess whether physical activity can predict mortality in patients undergoing maintenance hemodialysis (MHD). This observational study enrolled 317 patients undergoing MHD from Shanxi Provincial People Hospital and the Second Affiliated Hospital of Xi'an Medical University from February to June 2012. Physical activity was measured by using the Human Activity Profile (HAP) and the Stanford 7‐day Physical Activity Recall Questionnaire (PAR). Exercise or not, maximal activity score (MAS), adjusted activity score (AAS), light physical activities, moderate physical activities, and the PAR value were significantly associated with mortality among patients undergoing MHD. The patients with higher scores of maximal activity score (MAS), adjusted activity score (AAS), and PAR value; more hours of the light physical activities; and moderate physical activities have the lower mortality. Through multivariate Cox regression analysis, adjusting for age, MAS, PAR value, and light physical activities can predict the mortality among patients undergoing MHD (P < .05), and the relative risk values were 0.44, 0.69, and 0.66, respectively. Baseline physical activities are independent predictors of mortality in patients undergoing hemodialysis.
Un nouveau programme de recherche pour évaluer l'effet des dispositions relatives au travail contenues dans les accords de libre‐échange européens
Authors: CAMPLING Liam , HARRISON James , RICHARDSON Ben , SMITH Adrian
Published: December 2016

L'Union européenne a conclu à ce stade quelque cinquante accords de libre‐échange bilatéraux, auxquels une dizaine d'autres devraient s'ajouter prochainement. Ces textes comprennent désormais un chapitre intitulé «Commerce et développement durable», soit des dispositions relatives au travail d'une nature «promotionnelle» plutôt que «conditionnelle». Les auteurs s'attachent à préciser les atouts et les limites de cette association, parfois contestée ou jugée inefficace, entre objectifs commerciaux et objectifs sociaux, tout en soulignant l'insuffisance des connaissances en la matière. Pour y remédier, ils proposent un nouveau programme de recherche, aux fins d'une évaluation des effets concrets de ces dispositions relatives au travail dans les États partenaires.
Les droits au travail dans une économie mondialisée: les nouveaux modèles d'accords commerciaux et d'investissement des États‐Unis peuvent‐ils promouvoir les normes internationales du travail au Bangladesh?
Authors: BROWN Ronald C.
Published: December 2016

Les accords internationaux de libre‐échange ou d'investissement offrent des possibilités considérable – mais inexploitées – de renforcement des normes du travail. Les dispositions relatives au travail inscrites dans l'accord commercial États‐Unis‐République de Corée marquent une indéniable amélioration à cet égard. Cependant, selon l'auteur, l'efficacité de l'accord est amoindrie par des mécanismes d'exécution insuffisants et la formulation des droits par référence à la Déclaration de l'OIT de 1998 plutôt qu'aux conventions fondamentales sur lesquelles elle est fondée. L'auteur examine les mesures à adopter pour que ces accords contribuent effectivement au renforcement des normes relatives au travail partout dans le monde.
ANCIENT EGYPTIAN TEXTS IN CONTEXT. TOWARDS A CONCEPTUAL DATA MODEL (THE THOT DATA MODEL - TDM)
Authors: POLIS STÉPHANE , RAZANAJAO VINCENT
Published: December 2016

In this paper, we propose a conceptual data model which could be the basis for future implementations of databases and digital corpuses of Ancient Egyptian texts that fully integrate the material dimensions of writing. The types of metadata that can be used for documenting the elements and relationships of this model are discussed and the resources (URIs) available for its online implementation (in the perspective of the ‘linked open data’ movement) are examined.
NEW APPROACHES TO ANCIENT SPATIAL MODELS: DIGITAL HUMANITIES AND CLASSICAL GEOGRAPHY
Authors: PALLADINO CHIARA
Published: December 2016

This paper proposes a methodology to address the problem of the representation of Greek and Roman geography in the digital environment. As classical geography was not only a graphic representation of the world, but a multi-layered cultural system based on specific notions and concepts, it is now necessary to go beyond the taxonomy of place-names and their visualization on modern maps. The interpretation of ancient geography as a ‘mental model’ implies the importance of different and complementary aspects which should be addressed systematically: the expression of distances, the language of spatial orientation, the definition of environmental landmarks. For each of these aspects an integrated digital methodology is proposed, either implementing existing infrastructures or focusing on new strategies. The conclusion establishes a workflow to be tested on the corpus of the Geographi Graeci Minores, and extended to a variety of other texts.
MORPHOLOGICAL ANALYSIS OF HISTORICAL LANGUAGES
Authors: SMITH NEEL
Published: December 2016

This paper describes the design of a system for parsing ancient Greek morphologically, taking into account the distinctive requirements of studying a historical language. Sets of stems and inflectional patterns identified by URNs are expressed in a specified orthography, and are loaded dynamically when the parser is built. Analytical results are also expressed with URN values for lexical entity and form, so that replies identify both the result of the analysis and the logic leading to the result. The underlying engine uses finite transducers to collect possible analyses of Greek words stripped of accents. A wrapper program implements an ‘analysis by synthesis’ algorithm by adding appropriate accents for each candidate analysis, and comparing the result to the originally submitted form. Parsers can be built or tailored to specific corpora without programming, by editing tables of stems and inflectional patterns.
DOCUMENTING HOMERIC TEXT-REUSE IN THE DEIPNOSOPHISTAE OF ATHENAEUS OF NAUCRATIS
Authors: BERTI MONICA , BLACKWELL CHRISTOPHER , DANIELS MARY , STRICKLAND SAMANTHA , VINCENT-DOBBINS KIMBELL
Published: December 2016

In this article we discuss ongoing work on documenting text-reuse in the Deipnosophistae of Athenaeus of Naucratis. We present a data model for identifying uniquely instances of text-reuse that are as specific or non-specific as necessary, that can cover types of reuse from direct quotation, through paraphrase, to allusion, including instances where the reused text is non-contiguous. We illustrate our discussion with examples from our work, starting with six cases of reuses of Homer's Iliad in the Deipnosophistae. Our data model is developed on the Canonical Text Services (CTS), which is a protocol for identifying and retrieving passages of text based on concise, machine-actionable canonical citation. The data model consists of six fields, and we argue that each of these six is necessary, and that together they are sufficient.
Interarm blood pressure differences predict target organ damage in type 2 diabetes
Authors: Spannella Francesco , Giulietti Federico , Fedecostante Massimiliano , Ricci Maddalena , Balietti Paolo , Cocci Guido , Landi Laura , Bonfigli Anna Rita , Boemi Massimo , Espinosa Emma , Sarzani Riccardo
Published: December 2016

Patients with type 2 diabetes mellitus are at high risk for atherosclerotic disease, and proper blood pressure measurement is mandatory. The authors examined the prevalence of an interarm difference (IAD) in blood pressure and its association with cardiovascular risk factors and organ damage (nephropathy, retinopathy, left ventricular hypertrophy, and vascular damage) in a large diabetic population. A total of 800 consecutive patients with type 2 diabetes mellitus were evaluated with an automated simultaneous bilateral device (men: 422 [52.8%]; mean age: 68.1±12.2 years). Diabetic patients with systolic IAD ≥5 and systolic IAD ≥10 mm Hg showed an increased risk of having vascular damage (adjusted odds ratios: 1.73 and 2.49, respectively) and higher pulse pressure. IAD is highly prevalent in patients with diabetes, is associated with vascular damage, even for IAD ≥5 mm Hg, and should be accurately obtained to avoid underdiagnosis and undertreatment of hypertension.
Global analysis reveals that cryptic diversity is linked with habitat but not mode of life
Authors: Poulin R. , Pérez‐Ponce de León G.
Published: December 2016

The ubiquity of genetically distinct, cryptic species is limiting any attempt to estimate local or global biodiversity as well as impeding efforts to conserve species or control pests and diseases. Environmental factors or biological traits promoting rapid diversification into morphologically similar species remain unclear. Here, using a meta‐analysis of 1230 studies using DNA sequences to search for cryptic diversity in metazoan taxa, we test two hypotheses regarding the frequency of cryptic taxa based on mode of life and habitat. First, after correcting for study effort and accounting for higher taxonomic affinities and biogeographical region of origins, our results do not support the hypothesis that cryptic taxa are more frequent among parasitic than free‐living taxa. Second, in contrast, the results support the hypothesis that cryptic taxa are more common in certain habitats than others: for a given study effort, more cryptic taxa are found in freshwater than in terrestrial or marine taxa. These findings suggest that the greater heterogeneity and fragmentation of freshwater habitats may promote higher rates of genetic differentiation among its inhabitants, a general pattern with serious implications for freshwater conservation biology.
Ethical issues with colorectal cancer screening—a systematic review
Authors: Hofmann Bjørn
Published: December 2016

Rationale, aims, and objectives

Colorectal cancer (CRC) screening is widely recommended and implemented. However, sometimes CRC screening is not implemented despite good evidence, and some types of CRC screening are implemented despite lack of evidence. The objective of this article is to expose and elucidate relevant ethical issues in the literature on CRC screening that are important for open and transparent deliberation on CRC screening.

Methods

An axiological question‐based method is used for exposing and elucidating ethical issues relevant in HTA. A literature search in MEDLINE, Embase, PsycINFO, PubMed Bioethics subset, ISI Web of Knowledge, Bioethics Literature Database (BELIT), Ethics in Medicine (ETHMED), SIBIL Base dati di bioetica, LEWI Bibliographic Database on Ethics in the Sciences and Humanities, and EUROETHICS identified 870 references of which 114 were found relevant according to title and abstract. The content of the included papers were subject to ethical analysis to highlight the ethical issues, concerns, and arguments.

Results

A wide range of important ethical issues were identified. The main benefits are reduced relative CRC mortality rate, and potentially incidence rate, but there is no evidence of reduced absolute mortality rate. Potential harms are bleeding, perforation, false test results, overdetection, overdiagnosis, overtreatment (including unnecessary removal of polyps), and (rarely) death. Other important issues are related to autonomy and informed choice equity, justice, medicalization, and expanding disease.

Conclusion

A series of important ethical issues have been identified and need to be addressed in open and transparent deliberation on CRC screening.
Growth characteristics of the intracellular pathogen, Piscirickettsia salmonis, in tissue culture and cell‐free media
Authors: Makrinos D L , Bowden T J
Published: December 2016

Piscirickettsia salmonis is an intracellular bacterium that was first isolated and identified in fish cells. Several types of cell lines have been explored for their ability to provide the bacterium with a host cell to replicate in. Tissue culture has been used for growth and cultivation for nearly two decades, until the facultative nature of P. salmonis was confirmed upon the development of blood‐ and cysteine‐based agar. Since then, research has continued to drive the creation of novel agar and broth formulations in order to improve the efficacy of cultivation of P. salmonis. Until now, the techniques and components used for growth have not been thoroughly discussed. In this review, the methods and formulations for growth of P. salmonis in tissue culture and cell‐free media will be examined.
Elevated intracellular Na+ concentrations in developing spinal neurons
Authors: Lindsly Casie , Gonzalez‐Islas Carlos , Wenner Peter
Published: December 2016

Over 25 years ago it was first reported that intracellular chloride levels (Cl−in) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na+in) change during the development of non‐neural cells, it has largely been assumed that Na+in is the same in developing and mature neurons. Here, using the sodium indicator SBFI, we test this idea and find that Na+in is significantly higher in embryonic spinal motoneurons and interneurons than in maturity. We find that Na+in reaches ~ 60 mM in mid‐embryonic development and is then reduced to ~ 30 mM in late embryonic development. By retrogradely labeling motoneurons with SBFI we can reliably follow Na+in levels in vitro for hours. Bursts of spiking activity, and blocking voltage‐gated sodium channels did not influence observed motoneuron sodium levels. On the other hand, Na+in was reduced by blocking the Na+‐K+‐2Cl− cotransporter NKCC1, and was highly sensitive to changes in external Na+ and a blocker of the Na+/K+ ATPase. Our findings suggest that the Na+ gradient is weaker in embryonic neuronal development and strengthens in maturity in a manner similar to that of Cl−.

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RETURNS TO COLLEGE MAJORS ACROSS LARGE METROPOLITAN AREAS
Authors: Phelan Brian J. , Sander William
Published: December 2016

In this paper, we provide new evidence that earnings for various college majors differ across large metropolitan areas in the United States. We then set out to explain, at least in part, why these differences exist. We find that the intrinsic elements of geographic areas, such as common agglomeration effects and spatial differences in demand, are an important explanation for all majors. Further, we find that the endogenous sorting of individuals plays less of a role, particularly for domestic‐born college graduates. The sorting of lower‐paid, foreign‐born college graduates, however, increases the estimated dispersion in returns across geographic areas.
The Hispanic and Latino dentist workforce in the United States
Authors: Mertz Elizabeth , Wides Cynthia , Calvo Jean , Gates Paul
Published: December 2016

Objectives

The purpose of this paper is to describe the Hispanic/Latino (H/L) dentist workforce, their general practice patterns, and their contributions to oral health care for H/L and underserved patients.

Methods

A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 35.4 percent response rate for self‐reported H/L dentists. Data were weighted for selection and response bias to be nationally representative. A workforce profile of H/L dentists was created using descriptive and multivariable statistics and published data.

Results

Among all H/L dentists (weighted n = 5,748), 31.9 percent self‐identify their origin as Mexican, 13.4 percent as Puerto Rican, 13.0 percent as Cuban, and 41.7 percent as another H/L group. The largest share of H/L dentists are male, married, and have children under age 18. Fifty percent of H/L dentists are foreign‐born and 25 percent are foreign‐trained. H/L dentists report higher than average educational debt, with those completing International Dentist Programs reporting the highest debt load. Sixty‐nine percent of clinically active H/L dentists own their own practices, and 85 percent speak Spanish in their practice. Among clinical H/L dentists, 7 percent work in safety‐net settings, 40 percent primarily treat underserved populations, and, on average, 42 percent of their patient population is H/L.

Conclusions

H/L dental providers are underrepresented in the dentist population, and those that are in practice shoulder a disproportionate share of dental care for minority and underserved communities. Improving the workforce diversity of dental providers is a critical part of strategy to address the high burden of dental disease in the H/L population.
Configurations of Innovations across Domains: An Organizational Ambidexterity View
Authors: Zhang Feng , Wang Yonggui , Li Dahui , Cui Victor
Published: December 2016

How do firms balance explorative and exploitative innovation for superior firm performance? While most prior studies have approached this issue by focusing on technology‐related innovation, the role of balancing exploration and exploitation in other important organizational domains, i.e., marketing, and the interaction effect of ambidexterity across different domains have been overlooked. This study contributes to this line of research by investigating how firms simultaneously balance exploration and exploitation across two critical domains, namely technology innovation and market innovation. The study distinguishes four types of configurations: market leveraging (technology exploration and market exploitation), technology leveraging (technology exploitation and market exploration), pure exploitation (technology exploitation and market exploitation), and pure exploration (technology exploration and market exploration). From an organizational ambidexterity perspective, the current work investigates whether and how these different combinations exert distinctive effects on firm performance. Specifically, the article posits that (a) technology exploration and market exploitation complement each other, and (b) technology exploitation and market exploration also complement each other, such that both market leveraging and technology leveraging strategies have positive effects on firm performance. The article also maintains that such positive relationships are fully mediated by differentiation and low cost advantages. Conversely, it is argued that (c) technology exploration and market exploration conflict with each other, and (d) so do technology exploitation and market exploitation, such that both pure exploration and pure exploitation have negative effects on firm performance. Hypotheses were tested using survey data collected from 292 manufacturing and service firms in China. The results supported most of the hypotheses, except that pure exploration demonstrated no significant relationship with firm performance.
Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B
Authors: Pan C. Q. , Yi W. , Liu M. , Wan G. , Hu Y.‐H. , Zhou M.‐F.
Published: December 2016

There are little data on the timing of initiating lamivudine therapy for preventing transmission of hepatitis B in highly viremic mothers. Between May 2008 and January 2015, we retrospectively enrolled mothers with HBV DNA >6 log10 copies/mL who received lamivudine during pregnancy, and we compared them to untreated mothers. The primary measurement was the vertical transmission rate. The secondary outcomes were the mothers’ and infants’ safety. Among 249 consecutive mothers enrolled, 66 and 94 received lamivudine during the second and third trimesters, respectively, and 89 were untreated. At delivery, maternal mean HBV DNA levels were significantly lower in mothers who received lamivudine (4.45 log10; vs 7.16 log10 copies/mL; P<.001). Lamivudine treatment was well tolerated. However, early treatment during the second trimester did not significantly increase the percentage of mothers achieving HBV DNA levels of <6 log10 copies/mL compared to those treated during the third trimester (98.5% vs 94.7%; P=.40). At the age of 28 weeks, the vertical transmission rates were significantly lower in the lamivudine‐treated mothers vs in the untreated mothers (0% [0/160] vs 5.62% [5/89]; P<.001), but the rates were similar when comparing the two subgroups treated with lamivudine (0% [0/66] vs 0% [0/94], P>.05). The birth defect rates and mothers’ and infants’ adverse events were similar among the groups. Lamivudine treatment initiated in the second or third trimester for mothers with HBV DNA levels below 9 log10 copies/mL was equally safe and effective in preventing vertical transmission. Thus, lamivudine should be deferred until the third trimester to minimize foetal exposure and drug resistance.
HCV reinfection incidence among individuals treated for recent infection
Authors: Martinello M. , Grebely J. , Petoumenos K. , Gane E. , Hellard M. , Shaw D. , Sasadeusz J. , Applegate T. L. , Dore G. J. , Matthews G. V.
Published: December 2016

One challenge to HCV elimination through therapeutic intervention is reinfection. The aim of this analysis was to calculate the incidence of HCV reinfection among both HIV‐positive and HIV‐negative individuals treated for recent HCV infection (estimated infection duration <18 months). Individuals with recent HCV infection who achieved an end‐of‐treatment response in four open‐label studies between 2004 and 2015 in Australia and New Zealand were assessed for HCV reinfection, confirmed by sequencing of the Core‐E2 and/or NS5B regions. Reinfection incidence was calculated using person‐time of observation. Exact Poisson regression analysis was used to assess factors associated with HCV reinfection. The cohort at risk for reinfection (n=120; 83% male; median age 36 years) was composed of HIV‐positive men‐who‐have‐sex‐with‐men (53%) and people who inject drugs (current 49%, ever 69%). Total follow‐up time at risk was 135 person‐years (median 1.08 years, range 0.17, 2.53). Ten cases of HCV reinfection were identified, for an incidence of 7.4 per 100 py (95% CI 4.0, 13.8). Reinfection incidence was significantly higher among participants who reported injection drug use at end of or post‐treatment, irrespective of HIV status (15.5 per 100 py, 95% CI 7.8, 31.1). In adjusted analysis, factors associated with reinfection were older age (aIRR 5.3, 95% CI 1.15, 51.5, P=.042) and injection drug use at end of or post‐treatment (aIRR 7.9, 95% CI 1.6, 77.2, P=.008). High reinfection incidence following treatment for recent HCV infection in individuals with ongoing risk behaviour emphasizes the need for post‐treatment surveillance, harm reduction strategies and education in at‐risk populations.
Intrahepatic angiopoietin‐2 correlates with chronic hepatitis C progression and is induced in hepatitis C virus replicon systems
Authors: Hernández‐Bartolomé Ángel , López‐Rodríguez Rosario , García‐Buey Luisa , Martín‐Vílchez Samuel , Rodríguez‐Muñoz Yolanda , Borque María Jesús , González‐Moreno Leticia , Real‐Martínez Yolanda , Mendoza‐Ridruejo Jorge , Martín‐Pérez Elena , Moreno‐Otero Ricardo , Sanz‐Cameno Paloma
Published: December 2016

Background & Aims

Chronic hepatitis C (CHC) is a major cause of cirrhosis and hepatocellular carcinoma and angiogenesis is closely related to the pathogenesis and progression of different chronic liver diseases (CLD). Thus, the intrahepatic expression of angiopoietins 1 and 2 (Ang1 and Ang2), as relevant mediators of pathological angiogenesis in several CLD, was investigated. In addition, the differential influence of structural and non‐structural genomic regions of HCV on the expression of angiopoietins and the possible signalling involved were studied.

Methods

Ang1 and Ang2 expression was evaluated by western blotting and enzyme‐linked immunosorbent assay (ELISA) in liver homogenates of CHC patients (n=47) and uninfected subjects (n=8). Their association with disease progression (according to METAVIR classification) was assessed by Spearman's correlation. Statistical differences among the expression of angiopoietins at different CHC stages were calculated by Mann‐Whitney U‐test. Finally, the in vitro expression of Angiopoietins in HCV replicons (complete or non‐structural subgenomic) and the main signalling pathways involved were also examined.

Results

Ang2 levels were significantly higher in the liver of CHC patients compared to controls and significantly correlated with inflammation and fibrosis. Accordingly, an increased expression of Ang2 was found in all HCV replicons tested. Interestingly, the inhibition of MEK and PI3K signalling pathways exerted differential effects on Ang2 expression concerning to the genomic region of HCV.

Conclusions

Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.
Falling Short of Constitutional Norms: Does “Normative (In)Congruence” Explain the Courts' Inability to Promote the Right to Water in South Africa?
Authors: Stacey Richard
Published: December 2016

In South Africa, municipal noncompliance with legislation promoting the constitutional right to sufficient water is both a failure of the rule of law and a betrayal of that right. Judicial intervention has prompted formalistic compliance with water law, but the underlying commitment to sufficient water remains unfulfilled. Does the inability of courts to achieve social justice despite enforcing social legislation confirm the thesis that commitments to the rule of law and to social justice are inconsistent, that upholding the rule of law may not advance social justice? This article offers an alternative to this “inconsistency thesis,” arguing that the rule of law can accommodate social justice if it demandsnormative congruencealongside congruence with formal rules. Empirical investigation reveals that structural challenges and the multifarious normative demands on officials create a condition ofnormative incongruencethat impedes the pursuit of social justice, even as courts compel congruence with formal rules.
The New Rich and Their Unplanned Births: Stratified Reproduction under China's Birth‐planning Policy
Authors: Shi Lihong
Published: December 2016

This article explores the creation and ramifications of a stratified reproductive system under China's state control of reproduction. Within this system, an emerging group of “new rich” are able to circumvent birth regulations and have unplanned births because of their financial capabilities and social networks. While China's birth‐planning policy is meant to be enforced equally for all couples, the unequal access to wealth and bureaucratic power as a result of China's widening social polarization has created disparate reproductive rights and experiences. This article identifies three ways in which reproductive privileges are created. It further explores how a stratified reproductive system under state population control reinforces social polarization. While many socially marginalized couples are unable to register their unplanned children for citizenship status and social benefits, the new rich are able to legitimate their births and transfer their privilege and status to their children, thus reproducing a new generation of elites.
Pathways to School Readiness: Executive Functioning Predicts Academic and Social–Emotional Aspects of School Readiness
Authors: Mann Trisha D. , Hund Alycia M. , Hesson‐McInnis Matthew S. , Roman Zachary J.
Published: December 2016

The current study specified the extent to which hot and cool aspects of executive functioning predicted academic and social‐emotional indicators of school readiness. It was unique in focusing on positive aspects of social–emotional readiness, rather than problem behaviors. One hundred four 3–5‐year‐old children completed tasks measuring executive functioning, social–emotional readiness, academic readiness, and vocabulary. As expected, age predicted executive functioning components and social–emotional readiness. Moreover, working memory and inhibitory control directly predicted academic readiness, whereas delay of gratification predicted social–emotional readiness. Working memory and inhibitory control predicted delay of gratification, consistent with the notion that simpler executive functions may set the stage for more complex executive functions. Interestingly, social–emotional readiness predicted academic readiness. These findings confirm that hot and cool aspects of executive functioning are related to social–emotional and academic school readiness.
Health staff understanding, application, and interpretation of growth charts in Nigeria
Authors: Ezeofor Ifeyinwa O. , Garcia Ada L. , Ibeziako Stella N. , Mutoro Antonina N. , Wright Charlotte M.
Published: December 2016

We aimed to compare plotting accuracy and interpretation of weight gain patterns in average and small infants on road‐to‐health (RTH) and the new World Health Organization (WHO) growth charts in Enugu, Nigeria. Child health staff plotted standard weights on both formats. Twelve plotted charts were created, permutating three different weight trajectories (fast, steady, and slow) ending at two attained weights (average and small), with each plotted on both chart formats. Respondents were shown four of these charts and asked to describe the weight gain pattern shown and what action this pattern would prompt. There were 222 respondents, of whom 78% were hospital based; 54% were nurses, 32% medical doctors, and 13% nutritionists. Plotting accuracy was good on both the WHO and RTH charts, but rating of weight gain was generally poor. On the RTH chart, slow weight gain was correctly recognized in only 19% average and 35% small infants, and responses were not significantly associated with the pattern shown. On the WHO charts, slow weight gain was correctly recognized in 40% average and 65% small infants (p = .002 and <.001), but they were also more likely to rate small children with normal growth as slow weight gain. In a logistic regression model, final weight predicted a slow weight gain rating more strongly (OR = 2.4; 1.8–3.2) than an actual slow weight gain pattern (OR 1.8; 1.1–1.6). Health staff seemed unable to recognize slow weight gain and were influenced more by current weight than actual weight gain pattern, though the new WHO format improved recognition.
An allelic series at pax7a is associated with colour polymorphism diversity in Lake Malawi cichlid fish
Authors: Roberts Reade B. , Moore Emily C. , Kocher Thomas D.
Published: December 2016

Despite long‐standing interest in the evolution and maintenance of discrete phenotypic polymorphisms, the molecular genetic basis of such polymorphism in the wild is largely unknown. Female sex‐associated blotched colour polymorphisms found in cichlids of Lake Malawi, East Africa, represent a highly successful polymorphic phenotype, found and maintained in four genera across the geographic expanse of the lake. Previously, we identified an association with an allelic variant of the paired‐box transcription factor gene pax7a and blotched colour morphs in Lake Malawi cichlid fishes. Although a diverse range of blotched phenotypes are present in Lake Malawi cichlid species, they all appeared to result from an allele of pax7a that produces increased levels of transcript. Here, we examine the developmental and genetic basis of variation among blotched morphs. First, we confirm that pax7a‐associated blotch morphs result primarily from modulation of melanophore development and survival. From laboratory crosses and natural population studies, we identify at least three alleles of pax7a associated with discrete subtypes of blotched morphs, in addition to the ancestral pax7a allele. Genotypes at pax7a support initial evolution of a novel pax7a allele to produce the blotched class of morphs, followed by subsequent evolution of that pax7a blotched allele to produce additional alleles associated with discrete colour morphs. Variant alleles of pax7a produce different levels of pax7a transcript, correlating with pigmentation phenotype at the cellular level. This naturally selected allelic series should serve as a case study for understanding the molecular genetic control of pax7a expression and the evolution of sex‐associated alleles.
Cryptic diversity in a fig wasp community—morphologically differentiated species are sympatric but cryptic species are parapatric
Authors: Darwell C. T. , Cook J. M.
Published: December 2016

A key debate in ecology centres on the relative importance of niche and neutral processes in determining patterns of community assembly with particular focus on whether ecologically similar species with similar functional traits are able to coexist. Meanwhile, molecular studies are increasingly revealing morphologically indistinguishable cryptic species with presumably similar ecological roles. Determining the geographic distribution of such cryptic species provides opportunities to contrast predictions of niche vs. neutral models. Discovery of sympatric cryptic species increases alpha diversity and supports neutral models, while documentation of allopatric/parapatric cryptic species increases beta diversity and supports niche models. We tested these predictions using morphological and molecular data, coupled with environmental niche modelling analyses, of a fig wasp community along its 2700‐km latitudinal range. Molecular methods increased previous species diversity estimates from eight to eleven species, revealing morphologically cryptic species in each of the four wasp genera studied. Congeneric species pairs that were differentiated by a key morphological functional trait (ovipositor length) coexisted sympatrically over large areas. In contrast, morphologically similar species, with similar ovipositor lengths, typically showed parapatric ranges with very little overlap. Despite parapatric ranges, environmental niche models of cryptic congeneric pairs indicate large regions of potential sympatry, suggesting that competitive processes are important in determining the distributions of ecologically similar species. Niche processes appear to structure this insect community, and cryptic diversity may typically contribute mostly to beta rather than alpha diversity.
Genomic data detect corresponding signatures of population size change on an ecological time scale in two salamander species
Authors: Nunziata Schyler O. , Lance Stacey L. , Scott David E. , Lemmon Emily Moriarty , Weisrock David W.
Published: December 2016

Understanding the demography of species over recent history (e.g. <100 years) is critical in studies of ecology and evolution, but records of population history are rarely available. Surveying genetic variation is a potential alternative to census‐based estimates of population size, and can yield insight into the demography of a population. However, to assess the performance of genetic methods, it is important to compare their estimates of population history to known demography. Here, we leveraged the exceptional resources from a wetland with 37 years of amphibian mark–recapture data to study the utility of genetically based demographic inference on salamander species with documented population declines (Ambystoma talpoideum) and expansions (A. opacum), patterns that have been shown to be correlated with changes in wetland hydroperiod. We generated ddRAD data from two temporally sampled populations of A. opacum (1993, 2013) and A. talpoideum (1984, 2011) and used coalescent‐based demographic inference to compare alternate evolutionary models. For both species, demographic model inference supported population size changes that corroborated mark–recapture data. Parameter estimation in A. talpoideum was robust to our variations in analytical approach, while estimates for A. opacum were highly inconsistent, tempering our confidence in detecting a demographic trend in this species. Overall, our robust results in A. talpoideum suggest that genome‐based demographic inference has utility on an ecological scale, but researchers should also be cognizant that these methods may not work in all systems and evolutionary scenarios. Demographic inference may be an important tool for population monitoring and conservation management planning.
Making a queen: an epigenetic analysis of the robustness of the honeybee (Apis mellifera) queen developmental pathway
Authors: He Xu Jiang , Zhou Lin Bin , Pan Qi Zhong , Barron Andrew B. , Yan Wei Yu , Zeng Zhi Jiang
Published: December 2016

Specialized castes are considered a key reason for the evolutionary and ecological success of the social insect lifestyle. The most essential caste distinction is between the fertile queen and the sterile workers. Honeybee (Apis mellifera) workers and queens are not genetically distinct, rather these different phenotypes are the result of epigenetically regulated divergent developmental pathways. This is an important phenomenon in understanding the evolution of social insect societies. Here, we studied the genomic regulation of the worker and queen developmental pathways, and the robustness of the pathways by transplanting eggs or young larvae to queen cells. Queens could be successfully reared from worker larvae transplanted up to 3 days age, but queens reared from older worker larvae had decreased queen body size and weight compared with queens from transplanted eggs. Gene expression analysis showed that queens raised from worker larvae differed from queens raised from eggs in the expression of genes involved in the immune system, caste differentiation, body development and longevity. DNA methylation levels were also higher in 3‐day‐old queen larvae raised from worker larvae compared with that raised from transplanted eggs identifying a possible mechanism stabilizing the two developmental paths. We propose that environmental (nutrition and space) changes induced by the commercial rearing practice result in a suboptimal queen phenotype via epigenetic processes, which may potentially contribute to the evolution of queen–worker dimorphism. This also has potentially contributed to the global increase in honeybee colony failure rates.
Artificial microRNAs and synthetic trans‐acting small interfering RNAs interfere with viroid infection
Authors: Carbonell Alberto , Daròs José‐Antonio
Published: December 2016

Artificial microRNAs (amiRNAs) and synthetic trans‐acting small interfering RNAs (syn‐tasiRNAs) are two classes of artificial small RNAs (sRNAs) engineered to silence endogenous transcripts as well as viral RNAs in plants. Here, we explore the possibility of using amiRNAs and syn‐tasiRNAs to specifically interfere with infections by viroids, small (250–400‐nucleotide) non‐coding circular RNAs with compact secondary structure infecting a wide range of plant species. The combined use of recent high‐throughput methods for artificial sRNA construct generation and the Potato spindle tuber viroid (PSTVd)–Nicotiana benthamiana pathosystem allowed for the simple and time‐effective screening of multiple artificial sRNAs targeting sites distributed along PSTVd RNAs of (+) or (–) polarity. The majority of amiRNAs were highly active in agroinfiltrated leaves when co‐expressed with an infectious PSTVd transcript, as were syn‐tasiRNAs derived from a construct including the five most effective amiRNA sequences. A comparative analysis showed that the effects of the most effective amiRNA and of the syn‐tasiRNAs were similar in agroinfiltrated leaves, as well as in upper non‐agroinfiltrated leaves in which PSTVd accumulation was significantly delayed. These results suggest that amiRNAs and syn‐tasiRNAs can be used effectively to control viroid infections in plants.
Challenges in intergenerational caregiving for frail older people: A multiple case study
Authors: Lien Ya‐Fen , Huang Hui‐Man
Published: December 2016

Abstract

Families in Taiwan are considered central in caring for frail older people. However, rapid social changes are reshaping Taiwanese family values and structures. In this study, we explored the challenges of intergenerational families in caring for frail older people in Taiwan. Using a multiple‐case study, 32 participants representing 12 families comprising three or more generations participated in individual, semistructured interviews. A grounded theory technique was used for the data analysis. Four themes emerged in the findings: intergenerational and intragenerational disharmony, restrictions in the physical environment, financial caregiving burdens, and lack of support from the healthcare system. The findings can help raise awareness of filial caregiving obligations of aging family members that have shifted from a parent–child dyad to being shared across multiple generations in Taiwan. Intergenerational caregiving for frail older people has become a challenge for policies aimed at keeping the aging population in the community.