bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model‐based evaluation of single metrics for discriminating changes in rheumatoid arthritis disease activity
Authors: Wojciechowski Jessica , Wiese Michael D. , Proudman Susanna M. , Foster David J. R. , Upton Richard N. 
Published: January 2016

AimsComposite indices for quantifying rheumatoid arthritis (RA) disease activity such as the 28‐joint disease activity score (DAS28) are comprised of single parameters (‘metrics’) in various combinations. Population modelling methods were used to evaluate single metrics for their ability to reflect changes in disease activity with a view to understanding and improving composite indices.MethodsA total of 11 single metrics of RA disease activity (tender and swollen joint counts, acute phase reactants and global health, pain and physical function assessments) were obtained from 203 patients with recent onset RA. Participants received combination disease‐modifying anti‐rheumatic drugs (DMARDs) according to a treat‐to‐target approach with a pre‐defined protocol for treatment intensification. Models describing each metric's magnitude and variability of change from baseline to a single ‘treated’ state in the population were developed using nonmem®. Measures that displayed uniformly large changes between states across the population were ranked higher in terms of discriminatory capacity.ResultsJoint counts demonstrated a greater ability to discriminate changes in RA disease activity than others. Correlations between metrics demonstrated that erythrocyte sedimentation rate (ESR) had limited relationships with others for baseline scores and changes in RA disease activity (r generally < 0.2). However it appeared to be important in describing changes for those individuals where ESR levels were initially elevated.ConclusionIt appears unlikely that a single group of metrics may be suitable to capture disease activity changes across all RA patients and defining the most appropriate metric(s) for individual patients will be an important area of future research.
Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non‐obese volunteers
Authors: Chairat Kalayanee , Jittamala Podjanee , Hanpithakpong Warunee , Day Nicholas P. J. , White Nicholas J. , Pukrittayakamee Sasithon , Tarning Joel 
Published: January 2016

AimsThe aims of the present study were to compare the pharmacokinetics of oseltamivir and its active antiviral metabolite oseltamivir carboxylate in obese and non‐obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and oseltamivir carboxylate.MethodsThe population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese [body mass index (BMI) ≥30 kg m−2) and 12 non‐obese (BMI <30 kg m−2) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomized sequence. Concentration–time data were collected and analysed using nonlinear mixed‐effects modelling.ResultsThe pharmacokinetics of oseltamivir and oseltamivir carboxylate were described simultaneously by first‐order absorption, with a one‐compartment disposition model for oseltamivir, followed by a metabolism compartment and a one‐compartment disposition model for oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance {3.84% increase for each 10 ml min−1 increase in creatinine clearance [95% confidence interval (CI) 0.178%, 8.02%]}. Obese individuals had an approximately 25% (95% CI 24%, 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI 19%, 23%) and 10% higher oseltamivir carboxylate clearance (95% CI 9%, 11%) compared with non‐obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate.ConclusionsThe results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics.
Effects of extreme experimental drought and rewetting on CO2 and CH4 exchange in mesocosms of 14 European peatlands with different nitrogen and sulfur deposition
Authors: Estop‐Aragonés Cristian , Zając Katarzyna , Blodau Christian 
Published: January 2016

AbstractThe quantitative impact of intense drought and rewetting on gas exchange in ombrotrophic bogs is still uncertain. In particular, we lack studies investigating multitudes of sites with different soil properties and nitrogen (N) and sulfur (S) deposition under consistent environmental conditions. We explored the timing and magnitude of change in CO2 (Respiration, Gross Primary Production – GPP, and Net Exchange – NE) and CH4 fluxes during an initial wet, a prolonged dry (~100 days), and a subsequent wet period (~230 days) at 12 °C in 14 Sphagnum peat mesocosms collected in hollows from bogs in the UK, Ireland, Poland, and Slovakia. The relationship of N and S deposition with GPP, respiration, and CH4 exchange was investigated. Nitrogen deposition increased CO2 fluxes and GPP more than respiration, at least up to about 15 kg N ha−1 yr−1. All mesocosms became CO2 sources during drying and most of them when the entire annual period was considered. Response of GPP to drying was faster than that of respiration and contributed more to the change in NE; the effect was persistent and few sites recovered “predry” GPP by the end of the wet phase. Respiration was higher during the dry phase, but did not keep increasing as WT kept falling and peaked within the initial 33 days of drying; the change was larger when differences in humification with depth were small. CH4 fluxes strongly peaked during early drought and water table decline. After rewetting, methanogenesis recovered faster in dense peats, but CH4 fluxes remained low for several months, especially in peats with higher inorganic reduced sulfur content, where sulfate was generated and methanogenesis remained suppressed. Based on a range of European sites, the results support the idea that N and S deposition and intense drought can substantially affect greenhouse gas exchange on the annual scale.
Fighting in the Dark: Ideology and State Formation in Post‐Colonial Burma
Authors: Hein Min Ye Paing 
Published: January 2016

AbstractExtant major approaches to states and revolutions privilege the role of state practices and the character of war‐making in shaping modern state‐making in the Third World. Bringing the role of ideology into this analytical landscape of state‐making, this paper advances an alternative claim that ideological practices shape modern state structures and practices as well as the dynamics of political contention between the state and the revolutions. First, I argue that that intra‐movement ideological dynamics within the nationalist movement can have a profound impact on the structure and practices of the state. Using the writings of the party leaders, memoirs and official publications of the Burmese communist party, I maintain that subtle and specific ideological differences amongst the Burmese leftist movements generated organizational splits and internecine conflicts in the nationalist struggle, which exerted profound influences on the structures and practices of the Burmese state Secondly, relative ideological positions of the state and the revolutionary movements play an important role in shaping the dynamics of contention between the state and revolution. For example, an intimate web of ideological affinity between the nascent Burmese state and the Burmese leftist movements shaped the context and content of political contention between the state and these movements in the post‐colonial Burma. To address these issues empirically, the first part of the paper examines the formation and cementation of organizational linkages amongst Burmese leftist nationalists during the anti‐colonial struggle. The second part of the paper addresses specific and subtle ways in which ideological character and practices of the Burmese state and the Burmese Communist party shaped state practices and state structures in modern Burma as well as the dynamics of political contention between the state and the revolutionary movements.
An integrative review exploring decision‐making factors influencing mental health nurses in the use of restraint
Authors: Riahi S. , Thomson G. , Duxbury J. 
Published: January 2016

Accessible SummaryWhat is known on the subject?

There is emerging evidence highlighting the counter therapeutic impact of the use of restraint and promoting the minimization of this practice in mental health care.

Mental health nurses are often the professional group using restraint and understanding factors influencing their decision‐making becomes critical.

To date, there are no other published papers that have undertaken a similar broad search to review this topic.

What this paper adds to existing knowledge?

Eight emerging themes are identified as factors influencing mental health nurses decisions‐making in the use of restraint.

The themes are: ‘safety for all’, ‘restraint as a necessary intervention’, ‘restraint as a last resort’, ‘role conflict’, ‘maintaining control’, ‘staff composition’, ‘knowledge and perception of patient behaviours’, and ‘psychological impact’.

‘Last resort’ appears to be the mantra of acceptable restraint use, although, to date, there are no studies that specifically consider what this concept actually is.

What are the implications for practice?

These findings should be considered in the evaluation of the use of restraint in mental health settings and appropriate strategies placed to support shifting towards restraint minimization.

As the concept of ‘last resort’ is mentioned in many policies and guidelines internationally with no published understanding of what this means, research should prioritize this as a critical next step in restraint minimization efforts.

AbstractIntroductionWhile mechanical and manual restraint as an institutional method of control within mental health settings may be perceived to seem necessary at times, there is emergent literature highlighting the potential counter‐therapeutic impact of this practice for patients as well as staff. Nurses are the professional group who are most likely to use mechanical and manual restraint methods within mental health settings. In‐depth insights to understand what factors influence nurses’ decision‐making related to restraint use are therefore warranted.AimTo explore what influences mental health nurses’ decision‐making in the use of restraint.MethodAn integrative review using Cooper's framework was undertaken.ResultsEight emerging themes were identified: ‘safety for all’, ‘restraint as a necessary intervention’, ‘restraint as a last resort’, ‘role conflict’, ‘maintaining control’, ‘staff composition’, ‘knowledge and perception of patient behaviours’, and ‘psychological impact’. These themes highlight how mental health nurses’ decision‐making is influenced by ethical and safety responsibilities, as well as, interpersonal and staff‐related factors.ConclusionResearch to further understand the experience and actualization of ‘last resort’ in the use of restraint and to provide strategies to prevent restraint use in mental health settings are needed.
Addressing barriers to the prevention, diagnosis and treatment of hepatitis B and C in the face of persisting fiscal constraints in Europe: report from a high level conference
Authors: Papatheodoridis G. , Thomas H. C. , Golna C. , Bernardi M. , Carballo M. , Cornberg M. , Dalekos G. , Degertekin B. , Dourakis S. , Flisiak R. , Goldberg D. , Gore C. , Goulis I. , Hadziyannis S. , Kalamitsis G. , Kanavos P. , Kautz A. , Koskinas I. , Leite B. R. , Malliori M. , Manolakopoulos S. , Matičič M. , Papaevangelou V. , Pirona A. , Prati D. , Raptopoulou – Gigi M. , Reic T. , Robaeys G. , Schatz E. , Souliotis K. , Tountas Y. , Wiktor S. , Wilson D. , Yfantopoulos J. , Hatzakis A. 
Published: January 2016

SummaryIn the WHO–EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120 000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence‐based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost‐effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis.
Water Quality Prediction of Gangapur Reservoir (India) Using LS‐SVM and Genetic Programming
Authors: Jadhav Mrunalini Shivaji , Khare Kanchan Chandrashekhar , Warke Arundhati Suresh 
Published: January 2016

AbstractWater quality analysis involves analysis of physio‐chemical, biological and microbiological parameters that reflect the abiotic and biotic status of ecosystems. This assessment facilitates planning for the utilization, antipollution and conservation strategies for sustainable use of aquatic ecosystem. Many mathematical models are available for predicting water quality. They have complex structures and require detailed information about sources and receptors, which are difficult and non‐economical. Difficulties in applying mathematical models promote the application of alternative approaches for data‐driven techniques for analysis of the results.The present study focuses on water quality predictions for the Gangapur Reservoir for a 30 days in advance scenario, using genetic programming (GP) and least square support vector machines (LS‐SVMs). A data period of 11 years (2000–2011) of Gangapur Reservoir temporal water quality was evaluated. The data were taken from a single sampling point representing climatological, hydrological and surface water quality measurements. One of the most important steps in application of data‐driven technique is selection of significant input parameters. Genetic programming equations were used for selecting significant input parameters. These significant input parameters are used for 30 days advance predictions of faecal coliform. A performance analysis of GP and LS‐SVM models was carried out with the help of coefficient of determination, root‐mean‐square error and correlation coefficient. In the absence of availability of data, a typical situation for Indian case studies, the model runs were conducted with the use of available parameters. The developed models, along with their performance indicators, also are discussed.
Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication
Authors: Thenin-Houssier Suzie , de Vera Ian Mitchelle S. , Pedro-Rosa Laura , Brady Angela , Richard Audrey , Konnick Briana , Opp Silvana , Buffone Cindy , Fuhrmann Jakob , Kota Smitha , Billack Blase , Pietka-Ottlik Magdalena , Tellinghuisen Timothy , Choe Hyeryun , Spicer Timothy , Scampavia Louis , Diaz-Griffero Felipe , Kojetin Douglas J. , Valente Susana T. 
Published: January 2016

ABSTRACT

The human immunodeficiency virus type 1 (HIV-1) capsid plays crucial roles in HIV-1 replication and thus represents an excellent drug target. We developed a high-throughput screening method based on a time-resolved fluorescence resonance energy transfer (HTS-TR-FRET) assay, using the C-terminal domain (CTD) of HIV-1 capsid to identify inhibitors of capsid dimerization. This assay was used to screen a library of pharmacologically active compounds, composed of 1,280
in vivo
-active drugs, and identified ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], an organoselenium compound, as an inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of ebselen with the HIV-1 capsid CTD and dimer dissociation when ebselen is in 2-fold molar excess. Electrospray ionization mass spectrometry revealed that ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys198 and Cys218. This compound presents anti-HIV activity in single and multiple rounds of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells. Ebselen inhibits early viral postentry events of the HIV-1 life cycle by impairing the incoming capsid uncoating process. This compound also blocks infection of other retroviruses, such as Moloney murine leukemia virus and simian immunodeficiency virus, but displays no inhibitory activity against hepatitis C and influenza viruses. This study reports the use of TR-FRET screening to successfully identify a novel capsid inhibitor, ebselen, validating HIV-1 capsid as a promising target for drug development.
Imatinib reduces bone marrow fibrosis and overwhelms the adverse prognostic impact of reticulin formation in patients with chronic myeloid leukaemia
Authors: Tanrikulu Simsek Eda , Eskazan Ahmet Emre , Cengiz Mahir , Ar Muhlis Cem , Ekizoglu Seda , Salihoglu Ayse , Gulturk Emine , Elverdi Tugrul , Ongoren Aydin Seniz , Senem Demiroz Ahu , Buyru Ayse Nur , Baslar Zafer , Ozbek Ugur , Ferhanoglu Burhan , Aydin Yildiz , Tuzuner Nukhet , Soysal Teoman 
Published: January 2016

AimsBefore the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy.MethodsThe study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated.ResultsSevere MF (grade II–III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0–I) and severe (grade II–III) groups (p=0.278).ConclusionsAccording to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs.
European molecular epidemiology and strain diversity of feline calicivirus
Authors: Hou J. , Sánchez‐Vizcaíno F. , McGahie D. , Lesbros C. , Almeras T. , Howarth D. , O'Hara V. , Dawson S. , Radford A. D. 
Published: January 2016

Feline calicivirus (FCV) causes a variable syndrome of upper respiratory tract disease, mouth ulcers and lameness. A convenience‐based prospective sample of oropharyngeal swabs (n=426) was obtained from five countries (France, Germany, Greece, Portugal and the UK). The prevalence of FCV by virus isolation was 22.2 per cent. Multivariable analysis found that animals presenting with lymphoplasmacytic gingivitis stomatitis complex were more likely to test positive for FCV infection. Furthermore, vaccinated cats up to 48 months of age were significantly less likely to be infected with FCV than unvaccinated animals of similar ages. Phylogenetic analysis based on consensus sequences for the immunodominant region of the capsid gene from 72 FCV isolates identified 46 strains. Thirteen of the 14 strains with more than one sequence were restricted to individual regions or sites in individual countries; the exception was a strain present in two sites close to each other in France. Four strains were present in more than one household. Five colonies, four of which were rescue shelters, had multiple strains within them. Polymerase sequence suggested possible rare recombination events. These locally, nationally and internationally diverse FCV populations maintain a continuous challenge to the control of FCV infection and disease.
Why Computing Students Learn on Their Own
Authors: McCartney Robert , Boustedt Jonas , Eckerdal Anna , Sanders Kate , Thomas Lynda , Zander Carol 
Published: January 2016

In this article, we address the question of why computing students choose to learn computing topics on their own. A better understanding of why some students choose to learn on their own may help us to motivate other students to develop this important skill. In addition, it may help in curriculum design; if we need to leave some topics out of our expanding curriculum, a good choice might be those topics that students readily learn on their own.
Based on a thematic analysis of 17 semistructured interviews, we found that computing students’ motivations for self-directed learning fall into four general themes: projects, social and peer interactions, joy of learning, and fear. Under these, we describe several more specific subthemes, illustrated in the words of the students.
The project-related and social motivations are quite prominent. Although these motivations appear in the literature, they received greater emphasis from our interviewees. Perhaps most characteristic of computing is the motivation to learn to complete some project, both projects done for fun and projects required for school or work.