bluuebunny/crossref_metadata_2025 huggingface dataset:
Prioritizing variants in complete Hereditary Breast and Ovarian Cancer (HBOC) genes in patients lacking knownBRCAmutations
Authors: Caminsky Natasha G. , Mucaki Eliseos J. , Perri Ami M. , Lu Ruipeng , Knoll Joan H. M. , Rogan Peter K.
Published: February 2016

BRCA1andBRCA2testing for HBOC does not identify all pathogenic variants. Sequencing of 20 complete genes in HBOC patients with uninformative test results (N=287), including non-coding and flanking sequences ofATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51B, STK11, TP53, andXRCC2, identified 38,372 unique variants. We apply information theory (IT) to predict and prioritize non-coding variants of uncertain significance (VUS) in regulatory, coding, and intronic regions based on changes in binding sites in these genes. Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. We prioritized variants affecting the strengths of 10 splice sites (4 natural, 6 cryptic), 148 SRBS, 36 TFBS, and 31 RBBS. Three variants were also prioritized based on their predicted effects on mRNA secondary (2°) structure, and 17 for pseudoexon activation. Additionally, 4 frameshift, 2 in-frame deletions, and 5 stop-gain mutations were identified. When combined with pedigree information, complete gene sequence analysis can focus attention on a limited set of variants in a wide spectrum of functional mutation types for downstream functional and co-segregation analysis.
Next-generation sequencing in neuropathological diagnosis of infections of the nervous system
Authors: Salzberg Steven L. , Breitwieser Florian P. , Kumar Anupama , Hao Haiping , Burger Peter , Rodriguez Fausto J. , Lim Michael , Quiñones-Hinojosa Alfredo , Gallia Gary L. , Tornheim Jeffrey A. , Melia Michael T. , Sears Cynthia L. , Pardo Carlos A.
Published: February 2016

Objective

To determine the feasibility of next-generation sequencing (NGS) microbiome approaches in the diagnosis of infectious disorders in brain or spinal cord biopsies in patients with suspected central nervous system (CNS) infections.

Methods

In a prospective-pilot study, we applied NGS in combination with a new computational analysis pipeline to detect the presence of pathogenic microbes in brain or spinal cord biopsies from ten patients with neurological problems indicating possible infection but for whom conventional clinical and microbiology studies yielded negative or inconclusive results.

Results

Direct DNA and RNA sequencing of brain tissue biopsies generated 8.3 million to 29.1 million sequence reads per sample, which successfully identified with high confidence the infectious agent in three patients, identified possible pathogens in two more, and helped to understand neuropathological processes in three others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Validation techniques confirmed the pathogens identified by NGS in each of the three positive cases. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in eight of ten cases, and were non-contributory in the remaining two.

Conclusions

NGS-guided metagenomic studies of brain, spinal cord or meningeal biopsies offer the possibility for dramatic improvements in our ability to detect (or rule out) a wide range of CNS pathogens, with potential benefits in speed, sensitivity, and cost. NGS-based microbiome approaches present a major new opportunity to investigate the potential role of infectious pathogens in the pathogenesis of neuroinflammatory disorders.
Shannon: An Information-Optimal de Novo RNA-Seq Assembler
Authors: Kannan Sreeram , Hui Joseph , Mazooji Kayvon , Pachter Lior , Tse David
Published: February 2016

De novo assembly of short RNA-Seq reads into transcripts is challenging due to sequence similarities in transcriptomes arising from gene duplications and alternative splicing of transcripts. We present Shannon, an RNA-Seq assembler with an optimality guarantee derived from principles of information theory: Shannon reconstructs nearly all information-theoretically reconstructable transcripts. Shannon is based on a theory we develop for de novo RNA-Seq assembly that reveals differing abundances among transcripts to be the key, rather than the barrier, to effective assembly. The assembly problem is formulated as a sparsest-flow problem on a transcript graph, and the heart of Shannon is a novel iterative flow-decomposition algorithm. This algorithm provably solves the information-theoretically reconstructable instances in linear-time even though the general sparsest-flow problem is NP-hard. Shannon also incorporates several additional new algorithmic advances: a new error-correction algorithm based on successive cancelation, a multi-bridging algorithm that carefully utilizes read information in the k-mer de Bruijn graph, and an approximate graph partitioning algorithm to split the transcriptome de Bruijn graph into smaller components. In tests on large RNA-Seq datasets, Shannon obtains significant increases in sensitivity along with improvements in specificity in comparison to state-of-the-art assemblers.
Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires
Authors: Pogorelyy Mikhail V. , Elhanati Yuval , Marcou Quentin , Sycheva Anastasia L. , Komech Ekaterina A. , Nazarov Vadim I. , Britanova Olga V. , Chudakov Dmitriy M. , Mamedov Ilgar Z. , Lebedev Yuri B. , Mora Thierry , Walczak Aleksandra M.
Published: February 2016

The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a “public” repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pregnancy, and survive over long periods, providing the basis of the public repertoire.
Multi-dimensional structure function relationships in human β-cardiac myosin from population scale genetic variation
Authors: Homburger Julian R. , Green Eric M. , Caleshu Colleen , Sunitha Margaret , Taylor Rebecca , Ruppel Kathleen M. , Metpally Raghu ,   SHaRe Investigators, Colan Steven D. , Michels Michelle , Day Sharlene , Olivotto Iacopo , Bustamante Carlos D. , Dewey Frederick , Ho Carolyn Y. , Spudich James A. , Ashley Euan A.
Published: February 2016

Myosin motors are the fundamental force-generating element of muscle contraction. Variation in the human β-cardiac myosin gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 HCM patients to elucidate novel structure-function relationships within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein three-dimensional space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified another region enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as a myosin mesa. This surface is prominent in the pre-stroke model, but substantially reduced in size following the power stroke. Notably, HCM patients with variants in the enriched regions have earlier presentation and worse outcome than those with variants in other regions. In summary, this study provides a model for the combination of protein structure, large-scale genetic sequencing and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease.
Auditor switch decisions under forced auditor change: evidence from China
Authors: Kuo Li-Chun , Lin Chan-Jane , Lin Hsiao-Lun
Published: February 2016

Purpose

– From 2000 to 2007, 14 Chinese accounting firms had their audit licenses terminated or suspended for different reasons, forcing clients of these accounting firms to select new auditors within a short period of time. The purpose of this paper is to examine the auditor switching patterns and audit partner following decision of these clients and the effect of both client and (terminated or suspended) auditor characteristics on the auditor change decisions.

Design/methodology/approach

– By using 245 (191) clients of terminated or suspended audit firms, the authors apply logistic regressions to investigate clients’ switching decision (following decision).

Findings

– The empirical results indicate that state-owned enterprises tend not to switch to Big 4 audit firms; clients with dual shares tend to choose from the Big 4 for their succeeding audit firms. Moreover, companies whose preceding auditors received severe regulatory sanctions are less likely to switch to auditors of higher quality; companies who hired local auditors are more likely to follow their preceding audit partners as a result of forced auditor change.

Originality/value

– This study enriches forced auditor change literature by discussing both clients’ and preceding auditor’s attributes on clients’ switching and following decisions.
Ownership concentration, family control, and auditor choice
Authors: Darmadi Salim
Published: February 2016

Purpose

– The purpose of this paper is to extend the existing, yet limited, literature on the influence of ownership concentration and family control on the demands for high-quality audits. This study focusses on an emerging market, namely, Indonesia, where ownership concentration and family control are relatively higher than those in developed markets.

Design/methodology/approach

– The sample consists of 787 firm-year observations of public firms listed on the Indonesia Stock Exchange. Following prior studies, a firm is considered using a higher quality audit when its external auditor is one of the Big 4 audit firms. Logistic regressions are employed to test research hypotheses.

Findings

– Empirical evidence obtained reveals that firms with higher ownership concentration are more likely to hire a Big 4 auditor. Hence, in such firms, high-quality audits are employed to mitigate agency issues. However, when the controlling shareholder is a family, the association between ownership concentration and the demands for high-quality auditors turns negative, implying that family-controlled firms tend to sustain opaqueness gains by hiring lower quality auditors.

Originality/value

– Previous empirical studies examining the influence of ownership concentration and family control on auditor choice are relatively limited in the literature and are heavily focussed on developed economies. In addition, the present study is one of the first to investigate the association between family control and auditor choice in the context of a developing economy.
The GRID scale: a new tool for measuring service mixed satisfaction
Authors: Audrezet Alice , Olsen Svein Ottar , Tudoran Ana Alina
Published: February 2016

Purpose

The purpose of this study is to evaluate a bidimensional tool to measure overall service satisfaction: the evaluative space grid (GRID scale). The GRID scale provides a common measure for both positivity and negativity through 25 grid cells. The authors propose to use the GRID scale as an integrated measure of both satisfaction and dissatisfaction to capture mixed reactions or ambivalence.

Design/methodology/approach

Within a cross-sectional between-subjects survey design, this study compares overall satisfaction with bank services as measured on the GRID scale versus a traditional semantic differential (SD) scale.

Findings

The results show that the GRID scale performs as well as the SD scale with respect to different criteria, such as reliability and discriminant, convergent, nomological and predictive validity. However, it allows to measure separately indifference and ambivalence.

Practical implications

Such a distinction assists decision-makers with recommendations on different strategies not only to create customer loyalty based on satisfaction but also to encourage them to think how to decrease the levels of dissatisfaction and ambivalence.

Originality/value

The GRID scale would address survey needs of every business suffering from average performances. This tool provides them better in-depth overall satisfaction information, especially regarding the “middle-ground” customers.
Exploring the relationships between compassion at work, the evaluative perspective of positive work-related identity, service employee creativity, and job performance
Authors: Hur Won-Moo , Moon Taewon , Rhee Seung-Yoon
Published: February 2016

Purpose

This study examines whether compassion at work increases service employees’ job performance. More specifically, the purpose of this study is to show the mechanism through which experienced compassion in an organization affects the job performance of service employees.

Design/methodology/approach

The employees from a department store in South Korea were surveyed using a self-administered instrument for data collection. Out of 550 questionnaires, a total of 309 usable questionnaires were obtained after list-wise deletion, for a 61.6 per cent response rate.

Findings

The results of this study suggest that the evaluative perspective of positive work-related identity mediates the relationship between compassion at work and service employees’ job performance. In addition, the findings of this study demonstrate that there is significant mediating effect of service employee creativity on the relationship between compassion at work and job performance. Furthermore, the relationship between compassion at work and job performance was sequentially mediated by the evaluative perspective of positive work-related identity and the creativity of service employees.

Research limitations/implications

The common method variance in the self-reported variables imposes a need for caution in the interpretation of the findings. Future studies could avoid the problem of common method bias by, for example, using supervisor ratings of creativity and job performance. On the other hand, this study will add to the growing body of research on service marketing by highlighting the role of compassion at work to enhance service employees’ job performance.

Practical implications

This study offers new insight for practitioners (i.e. CEOs, top management teams, employees) by suggesting that they may promote service employees’ job performance if they pay more attention to compassionate acts in service marketing.

Originality/value

As services are becoming more important and harder to sell simultaneously, this study provides a new perspective to improve service employees’ job performance by examining its link with compassion at work.
Examining customer evaluations across different self-service technologies
Authors: Robertson Nichola , McDonald Heath , Leckie Civilai , McQuilken Lisa
Published: February 2016

Purpose

This study aims to examine the influence of different self-service technologies (SSTs) on customer satisfaction with and continued usage of SSTs. Specifically, it compares an interactive voice response (IVR) SST and an online SST from the same provider to assess how to manage these parallel SSTs.

Design/methodology/approach

A tracking study was used, beginning with a survey of n = 957 SST users to test a model pertaining to SST satisfaction across IVR and online SSTs. These SST users were then tracked over 12 months. The association between customer satisfaction with and continued usage of the SSTs was examined using behavioural data from the service provider.

Findings

While the overall model was found to be valid across both types of SSTs, perceptions of factors including ease of use, perceived control and reliability differed for IVR and online SSTs. Satisfaction with SSTs is linked with users’ continued use of SSTs, but is not a barrier to users’ adoption of newer SST forms.

Research limitations/implications

Highlighting the rapid developments in this field, a new SST was introduced by the provider to respondents during the 12-month tracking period, thus complicating the results. Further studies could include the customer purpose for using SSTs as a variable.

Practical implications

The findings offer support for organisations offering a suite of SSTs, even if they serve the same purpose. Customers evaluate SST types differently, and even satisfied SST users switch to different SSTs when they become available. Allowing customers to choose the SST that best suits them appears to be good practice.

Originality/value

This study develops a comprehensive model of customer SST satisfaction that is used to undertake a comparison of two different types of SSTs, which has been missing from prior research.
Retrospective: tracking service failures and employee recovery efforts
Authors: Hoffman K. Douglas , Kelley Scott W. , Rotalsky Holly M.
Published: February 2016

Purpose

The purpose of this paper is to provide an evaluation of the findings first put forward in the article Tracking Service Failures and Employee Recovery Efforts with the benefit of hindsight, and to offer directions for further research and developments in the research area.

Design/methodology/approach

Research directions which emanated from the publication of the article have been examined in light of current service(s) marketing theory and practice. As a result, promising current and future strands of research have been identified.

Findings

The original study yielded the initial steps into what has become a systematic step-by-step process that outlines the development and implementation of a service recovery program that now includes failure identification; failure attribution; recovery strategy selection; recovery implementation; and tracking, monitoring and evaluating effectiveness. Subsequent research has linked organistic and mechanistic components of a recovery program to important customer and financial outcomes and the development of a service recovery audit.

Practical/implications

The original study served as a starting point for the development of a set of implications for services marketing practitioners. Specifically, as a result of the original research, a programmatic approach to service recovery was developed that includes the systematic process of failure identification; failure attribution; recovery strategy selection; (4) recovery implementation; and tracking, monitoring and evaluating effectiveness.

Originality/value

The original article was highly rated, and generated discussion and important further research. It has value as a part of the history of service(s) marketing research. The retrospective analysis by the author(s) gives a unique insight into processes and thinking associated with understanding key aspects that contribute to the historical development of service(s) marketing, and provides substantial food for thought for future research directions.
A comprehensive review of open innovation literature
Authors: Hossain Mokter , Islam K.M. Zahidul , Sayeed Mohammad Abu , Kauranen Ilkka
Published: February 2016

Purpose

– The purpose of this study is to pursue a comprehensive review of the progress of open innovation literature.

Design/methodology/approach

– Using a wide range of literature sources, altogether 293 articles relevant to the study’s objective were identified for statistical analysis. Moreover, contributory articles published from 2003 to June 2015 were included for content analysis.

Findings

– The study contributes in two ways. First, based on content analysis of the selected contributory articles, the authors shed light on the overall development of the open innovation literature and highlight the findings of significant studies. Second, the authors provide a detailed picture of the progress of open innovation literature by analyzing the comprehensive set of articles. Total yearly publication activity was calculated, and publication activity in different disciplines was addressed. The study unveils most influential articles, authors and journals that have discussed open innovation. The geographical locations of influential articles and authors are revealed. Additionally, frequently used keywords are listed.

Originality/value

– The authors present a new framework of open innovation research, highlight the progress of existing research and suggest avenues for future research.
Research on the key success factors of reverse innovation of the latecomer engineering and technical services enterprises
Authors: Xu Nana , Xu Yusen
Published: February 2016

Purpose

– Reverse innovation plays an important role in the innovation catch-up by latecomer enterprise. With the development of economic globalization, reverse innovation of the latecomer enterprise research has received increased attention day by day. The purpose of this paper is to reveal the key success factors and the realization mechanism of reverse innovation of the latecomer engineering and technical services enterprise.

Design/methodology/approach

– This paper adopts the grounded theory analysis as the research method, by analyzing the phenomenon, collating the results, mining through the systematic data and verifying the theory temporarily. Therefore, it is ideal for the research to build the theory by analyzing the phenomenon. Before the serious coding begins, the reliability of coders is first examined. Coders extract some sample as the first test sample; then, three coders code according to the description and requirements and calculate the coding results according to the formulas that the noted scholar Holsti has proposed. Then, the authors perform the coding three times that include open coding, axial coding and selective coding, and then, the key factor model of reverse innovation of the engineering and technical service enterprise is refined.

Findings

– The investigation reveals that technology localization, connection with the international market and industrial chain integration are the key success factors of reverse innovation of the latecomer engineering and technological service enterprise. Meanwhile, the latecomer enterprise gives full attention to local comprehensive comparative advantage to carry out technology localization during the reverse innovation. The diversified international coupling mechanism is an important support for technology localization. The engineering and technical service enterprise needs to pay attention to the service chain of the vertical integration in the process of reverse innovation.

Originality/value

– The paper enriches the related research of reverse innovation based on a new industry and provides management support for innovation catch-up of the latecomer enterprises that have a big technological gap when compared with the multi-national companies.
Initiating quality management in a small company
Authors: Assarlind Marcus , Gremyr Ida
Published: February 2016

Purpose

– The purpose of this paper is to identify critical aspects of quality management (QM) adoption in a small company. QM is more widely applied in large companies than in small ones. Previous research has pointed to QM ideas as sound and valid for small companies, but that many such initiatives fail because of poor implementation. With scarcity of resources and expertise, it is critical to study how QM can be initiated in small companies with often sceptical owner-managers.

Design/methodology/approach

– This paper is based on a single case study of a small company; data has been collected through two sets of interviews: one in late 2009 and one in mid-2012, as well as project reports and public financial data. This allows for a study of the adoption process over time.

Findings

– This study points to four critical areas when initiating QM work in a small company: the importance of initiation, the importance of contextualisation, QM adoption as an iterative process, and the need for external support.

Originality/value

– This paper highlights the importance of overcoming small business owners’ reluctance towards QM. Most research on QM initiatives in small companies has focused on the stages that follow an actual decision to begin a QM initiative. This paper shows that it is critical to carefully consider the stages leading to the decision. Further, it contributes with a case study on a small company, otherwise uncommon in QM research.
The role of value and virtues in TQM: an overview of literature
Authors: Moccia Salvatore
Published: February 2016

Purpose

– The purpose of this paper is to analyze the relation between values and virtues and the principles of Total Quality Management (TQM) and thus to propose a tentative framework of relationships.

Design/methodology/approach

– The paper is conceptual. It reviews some lists of values present in literature, and summarizes them in a more comprehensive list. Then the list of values is summarized in conjunction with a list of core virtues. Thus, it tries to explain the relation between them and the principles of TQM, passing through the two mediating variables passion and trust.

Findings

– A model of TQM based on core virtues is proposed.

Research limitations/implications

– The lack of empirical data that can validate the model.

Practical implications

– Considering the emphasis placed on virtues, the model can have some practical implications in the field of recruitment, promotion, and leadership.

Originality/value

– The paper attempts to link values and virtues to the principles of TQM by developing a model of interactions. A novel framework that can provide a basis for further research into the profound nature of quality management has been proposed. Furthermore, some implications that should be useful for recruiters and managers are discussed.
Heterogeneity in pathogen transmission: mechanisms and methodology
Authors: VanderWaal Kimberly L. , Ezenwa Vanessa O.
Published: February 2016

Heterogeneity in the ability of hosts to transmit pathogens is among the most fundamental concepts in disease dynamics and has major implications for disease control strategies.

The number of secondary infections produced by an infected individual is a function of three components: an individual's infectiousness, the rate at which it contacts susceptible individuals and the duration of infection. Individual‐level variation can emerge in each of these components through a combination of behavioural and physiological mechanisms.

In this review, we describe mechanisms that promote variation in the number of individuals to which an individual transmits a pathogen,emphasizing insights that can be gained by understanding which components of transmission (infectiousness, contact rate, infection duration) are primarily affected. We also discuss how behavioural and physiological processes generate transmission heterogeneities across multiple scales, from individual‐level variation to heterogeneity among species.

Strategies for quantifying each transmission component are presented, and we discuss why studies focusing on only one component of the infection process may be misleading.

To conclude, we describe how future research focusing on variation in transmission across all three components can provide a more holistic view of heterogeneity in pathogen transmission.
Barriers and enablers to integrating maternal and child health services to antenatal care in low and middle income countries
Authors: de Jongh TE , Gurol‐Urganci I , Allen E , Jiayue Zhu N , Atun R
Published: February 2016

Antenatal care (ANC) represents a delivery platform for a broad range of health services; however, these opportunities are insufficiently utilised. This review explores key barriers and enablers for successful integration of health s"ervices with ANC in different contexts. Data from peer‐reviewed and grey literature were organised using the SURE checklist. We identified 46 reports focusing on integration of HIV, tuberculosis, malaria, syphilis or nutrition services with ANC from Asia, Africa and the Pacific. Perspectives of service users and providers, social and political factors, and health system characteristics (such as resource availability and organisational structures) affected ease of integration.

Tweetable abstract

Health system factors, context and stakeholders must be considered for integrated antenatal care services.
Climate Change, Migration and the Cosmopolitan Dilemma
Authors: Held David
Published: February 2016

At its simplest, migration refers to the movement of people and their temporary or permanent geographical relocation. People have always been on the move and they have moved over great distances. In this article I set out a brief historical understanding of migration, and then focus on Europe and, finally, current dilemmas of European migration policy. In an era of climate change, war and uneven development, the pressures of migration have grown and could soon create an ever greater avalanche of movement. States act in a paradoxical way. On the one hand, they recognise the nature of the migration crisis and the necessity to broaden the definition of those who need urgent assistance. On the other hand, most host countries act on increasingly narrow definitions of those who warrant assistance and perhaps resettlement. This dilemma is examined and tentative steps are set down to show how it might be resolved.
Prevalence and determinants of medication non‐adherence in chronic pain patients: a systematic review
Authors: Timmerman L. , Stronks D. L. , Groeneweg J. G. , Huygen F. J.
Published: February 2016

Background

Chronic pain is commonly treated with analgesic medication. Non‐adherence to prescribed pain medication is very common and may result in sub‐optimal treatment outcome. The aim of this review was to investigate the prevalence of medication non‐adherence and to present determinants that may help identify patients at risk for non‐adherence to analgesic medication.

Methods

A search was performed in PubMed and Embase with systematic approach including PRISMA recommendations. Individual risk of bias was assessed and systematic data extraction was performed.

Results

Twenty‐five studies were included. Non‐adherence rates to pain prescriptions ranged from 8% to 62% with a weighted mean of 40%. Underuse of pain medication was more common than overuse in most studies. Factors that were commonly positively associated with non‐adherence were dosing frequency, polymedication, pain intensity, and concerns about pain medication. Factors negatively associated with non‐adherence were age, again pain intensity and quality of the patient–caregiver relationship. Underuse was positively associated with active coping strategies and self‐medication, and negatively associated with perceived need for analgesic medication. Overuse was positively associated with perceived need, pain intensity, opioid use, number of prescribed analgesics, a history of drug abuse, and smoking.

Conclusion

Non‐adherence to analgesic medication use is very common in the chronic pain population. The choice for pharmacological therapy should not only be based upon pain diagnosis but should also take the risks of non‐adherence into account. The value of adherence monitoring or adherence enhancing interventions has to be investigated in future studies.
Chronic non‐cancer pain and the epidemic prescription of opioids in the Danish population: trends from 2000 to 2013
Authors: Birke H. , Kurita G. P. , Sjøgren P. , Højsted J. , Simonsen M. K. , Juel K. , Ekholm O.
Published: February 2016

Background

Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non‐cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD‐related drugs in the Danish population.

Methods

Data from the cross‐sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals ≥16 years (response rates: 51–63%). Respondents completed a self‐administered questionnaire, which included the analyzed items on identification of chronic pain (≥6 months).

Results

From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non‐Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD‐related drugs decreased (13%) from 2010 to 2013, still one‐third of long‐term opioid user were co‐medicated with these drugs.

Conclusions

The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD‐related drugs has decreased from 2010 to 2013, but still one‐third of long‐term opioid users were co‐medicated.
Longitudinal association between cognitive performance and obsessive–compulsive symptoms in patients with psychosis and unaffected siblings
Authors: Schirmbeck F. , Swets M. , Meijer C. J. , Zink M. , de Haan L. ,   GROUP Investigators
Published: February 2016

Objective

Obsessive–compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross‐sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning.

Method

Baseline and follow‐up data from 622 patients and 670 un‐affected siblings from the ‘Genetic Risk and Outcome in Psychosis’ study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains.

Results

Cross‐sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set‐shifting abilities in patient who reported OCS development at follow‐up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit‐symbol coding in patients and siblings who reported remission of OCS.

Conclusion

Although insight into causality needs further exploration, our results do not confirm the hypothesis of pre‐existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed.
Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene
Authors: Otten Roy , Huizink Anja C. , Monshouwer Karin , Creemers Hanneke E. , Onrust Simone
Published: February 2016

There is substantial evidence for the assumption that particularly heavy cannabis usett is associated with a variety of psychopathologic conditions. Little is known about the relationship between cannabis and anxiety. Prior studies have concluded that cannabis use alone is not sufficient for the development of long‐term anxiety, and it has been suggested that cannabis is simply a risk factor that operates in conjunction with other risk factors. One such risk factor may be an individuals' genetic vulnerability. The present study examines the relationship between cannabis use and symptoms of anxiety by taking a developmental molecular‐genetic perspective with a focus on a polymorphism involved in the regulation of serotonin. Specifically, we concentrated on changes in cannabis use and symptoms of anxiety over time and differences herein for individuals with and without the short allele of the 5‐HTTLPR genotype. Data were from 1424 adolescents over a period of 5 years. We used different statistical analyses to test co‐development of cannabis use and symptoms of anxiety throughout adolescence and the possible role of the 5‐HTTLPR genotype in this process. Results from different analyses showed that cannabis use is associated with an increase in symptoms of anxiety, but only in carriers of the short allele of the 5‐HTTLPR genotype, not in non‐carriers. The findings of the present study show first evidence that the links between cannabis use and symptoms of anxiety are conditional on the individuals' genetic make‐up.
Re‐evaluating fall cankerworm management thresholds for urban and suburban forests
Authors: Walter Jonathan A. , Finch Frank T. , Johnson Derek M.
Published: February 2016

In recent decades, outbreaks of fall cankerworm (Alsophila pometaria, Lepidoptera: Geometridae) have increased in urban and suburban areas of the mid‐Atlantic and southeastern U.S.A., including in Richmond, Virginia, as well as in Charlotte, North Carolina.

Managers in these regions commonly monitor fall cankerworm population trends using sticky band traps and use established thresholds relating the number of individuals captured to defoliation as a decision‐making tool. For this pest, defoliation thresholds were established based on large forest tracts, although these may yield inaccurate predictions in urban and suburban landscapes.

Analyses of defoliation and fall cankerworm sticky band traps in Fairfax County, Virginia, U.S.A., indicate that trees with >200 female moths have >50% probability of being defoliated at moderate or greater intensity. This threshold is much larger than the threshold of 45 females previously established for large forest tracts, and a statistical model based on this established threshold proved an extremely poor fit to the data. In addition, we found little spatial correlation in fall cankerworm abundance among trap locations, in contrast to an established rule of thumb proposing that one trap per 40 ha can estimate fall cankerworm abundance for areas over 400 ha.

These findings highlight the importance of the ecological context in which management recommendations are made.
Cape ground squirrels as ecosystem engineers: modifying habitat for plants, small mammals and beetles in Namib Desert grasslands
Authors: Ewacha Michelle V. A. , Kaapehi Corris , Waterman Jane M. , Roth James D.
Published: February 2016

Burrowing and foraging of semi‐fossorial rodents can affect species distribution and composition. Ground squirrels dig large burrow systems for refuge from predators and temperature extremes. Burrowing and foraging around burrows by squirrels may affect habitat and resource distributions for other organisms. We examined the impact of Cape ground squirrels (Xerus inauris) on vegetation, small mammals and beetles during winter and summer in grasslands on the edge of the Namib Desert. At each burrow system and paired control site without burrows, we estimated plant cover and height using quadrats (N = 8 paired sites), small mammal abundance and species richness using mark‐recapture techniques (N = 8 paired sites) and beetle abundance and species richness using pitfall traps (N = 6 paired sites, winter only). Squirrel burrowing and foraging activities resulted in lower plant cover and height, higher small mammal abundance and lower beetle abundance and species richness. Squirrels also reduced more plant cover in winter compared to summer, but had no effect on small mammal species richness. Furthermore, plant cover and height were higher in summer, whereas small mammal abundance and species richness were higher in winter. Our results suggest that Cape ground squirrels are important ecosystem engineers that influence plant and animal communities in the Namib Desert grasslands.
Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non‐streptococcal toxic shock syndrome transition in the novel‐type Streptococcus pyogenes isolates that lost a salRK
Authors: Tatsuno Ichiro , Okada Ryo , Matsumoto Masakado , Hata Nanako , Matsui Hideyuki , Zhang Yan , Isaka Masanori , Hasegawa Tadao
Published: February 2016

Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Mutations in covR/S or rgg, negative regulators, can reportedly modulate the severity of infection in this pathogen. Recently, we showed that the regions encoding the SalR–SalK, a two‐component regulatory system, were deleted in some emm 1‐type isolates (named as ‘novel‐type’). In this study, the two novel ‘STSS’ isolates 10–85stss and 11–171stss were more virulent than the two novel ‘non‐STSS’ isolates 11O‐2non and 11T‐3non when examined using a mouse model of invasive infection. Genome‐sequencing experiments using the three strains 10–85stss, 11–171stss, and 11O‐2non detected only one single nucleotide polymorphism that causes a non‐synonymous mutation in fabT encoding a transcriptional regulator in strain 11O‐2non. Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non‐STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O‐2non, suggesting that the mutation in fabT, but not in covR/S or rgg, is involved in the differential virulence among the novel‐type clinical isolates. This type of non‐synonymous fabT mutation was also identified in 12 non‐STSS isolates (including 11O‐2non and 11T‐3non), and most of those 12 isolates showed impaired FabT function.
Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery
Authors: Van Driest Sara L. , Marshall Matthew D. , Hachey Brian , Beck Cole , Crum Kim , Owen Jill , Smith Andrew H. , Kannankeril Prince J. , Woodworth Alison , Caprioli Richard M. , Choi Leena
Published: February 2016

Aims

One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples.

Methods

We measured fentanyl concentrations in plasma from leftover clinically‐obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness‐of‐fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model‐driven weight‐adjusted per kg vs. fixed per kg fentanyl dosing.

Results

Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h–1 (2.2–9.2 l h–1), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter‐individual variability remained. In simulation studies, model‐driven weight‐adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing.

Conclusions

We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens.
Long‐term cognitive and school outcomes of late‐preterm and early‐term births: a systematic review
Authors: Chan E. , Leong P. , Malouf R. , Quigley M. A.
Published: February 2016

Background

Children born before full term (39–41 weeks' gestation) are at increased risk of adverse cognitive outcomes. Risk quantification is important as late‐preterm (LPT; 34–36 weeks) and early‐term (ET; 37–38 weeks) births are common.

Method

This review analyses the effect of LPT and ET births on long‐term cognitive and educational outcomes. The primary outcome was general cognitive ability. Secondary outcomes included verbal/non‐verbal intelligence quotient, subject‐specific school performance and special educational needs. The search strategy included Medline and Embase from January 1975 to June 2013. Eligible studies investigated specified outcomes and included suitable gestational age participants assessed at 2 years and older. Outcome measures and socio‐demographic descriptors were extracted, and data meta‐analysed where possible.

Results

Eight studies compared ET birth with full‐term birth. Fourteen studies compared LPT birth with either term birth (>37 weeks, n = 12 studies) or full‐term birth (39–41 weeks, n = 2 studies). Substantial between‐study heterogeneity existed. LPT and ET children underperformed in most outcomes compared with their term/full‐term counterparts, respectively. For example, LPT children had an increased risk of lower general cognitive ability (adjusted risk ratio 1.38 [95% confidence interval 1.06–1.79]), and full‐term children performed 5% of a standard deviation higher (z‐score 0.05 [0.02, 0.08]) than ET children. Poorer outcomes persist into adulthood; term cohorts performed 5% of a standard deviation higher than LPT cohorts (z‐score 0.05 [0.04, 0.07]), and full‐term cohorts performed 3% of a standard deviation higher than ET cohorts (z‐score 0.03 [0.02, 0.04]).

Conclusion

This review critically examines the knowledge around long‐term cognitive outcomes of LPT and ET births, demonstrating multiple, small, adverse differences between LPT/ET and term/full‐term births.