bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences with an adaptive design for a dose-finding study in osteoarthritis
Authors: Miller F. , Björnsson M. , Svensson O. , Karlsten R. 
Published: July 2014

Abstract

Aims
Many new potential medicines fail in early clinical development. AZD1386 is a TRPV1 antagonist and was developed for treatment of osteoarthritis pain at AstraZeneca. Following preclinical studies to characterize the compound, translational studies and first time in man studies the challenge is great to select the right doses and study population for the first clinical studies on efficacy in phase II of the drug development process.

Methods
Different design alternatives in the planning of the dose-finding study for AZD1386 in OA were analysed with regard to statistical considerations, timelines and costs for the different options.

Results
Based on datasimulations and cost/benefit analysis a 4 week study with adaptive design with interim analysis at 2 weeks for possible dose adjustment or futility stop was chosen. The study was initiated with AZD1386 at to doses 30 and 90 mg and placebo. Based on the fact that the one-sided p-value for the primary analysis (comparison of 90 mg versus placebo) was 0.2891 and larger than 0.2, the data monitoring committee decided that the study was to be stopped after the interim analysis due to lack of efficacy.

Conclusions
The chosen adaptive design in this Phase IIa/b study enabled an early futility stop. This meant several advantages. Further exposure of patients of a non-efficacious drug could be stopped and resources could be re-allocated earlier as well as monetary savings.
Chronic whiplash, pain and pain tolerance
Authors: Myrtveit Solbjørg Makalani , Skogen Jens Christoffer , Sivertsen Børge , Steingrímsdóttir Ólöf Anna , Stubhaug Audun , Nielsen Christopher Sivert 
Published: July 2014

Abstract

Aim
Among individuals who experience whiplash accidents, around 20% develop chronic pain. We aimed to compare number of painful locations and pain intensity between individuals with chronic whiplash and individuals with other chronic pain, and to investigate whether differences could be explained by pain tolerance.

Methods
Employing data from the sixth wave of the Tromsø Study, individuals reporting whiplash were compared to individuals with other chronic pain. Number of pain locations was compared using Poisson regression, pain intensity using linear regression. Pain tolerance (cold-pressor test) was compared using cox regression; one model compared individuals with whiplash to those with other chronic pain, another model compared the two groups with chronic pain to pain-free controls. In order to investigate whether pain tolerance could account for differences in pain, the regression models were adjusted for time-till-failure in the cold-pressor test.

Results
Individuals with whiplash reported a higher number of painful locations (IRR = 5.23, 95%CI: 4.93–5.53 versus IRR = 3.57, 95%CI: 3.50–3.65) and higher pain intensity (mean: 7.80, 95%CI: 7.58–8.02 versus mean: 7.14, 95%CI: 7.08–7.21) than individuals with other chronic pain. Pain tolerance did not differ between these two groups, but compared to pain-free controls individuals in both groups had reduced pain tolerance.

Conclusions
Individuals with chronic whiplash had reduced pain tolerance compared to individuals without chronic pain, but not compared to individuals with other chronic pain. Reduced pain tolerance can account for some of the increased pain reported by individuals with chronic whiplash compared to controls but not compared to individuals with other chronic pain.
Quality pain management in the hospital setting—A concept evaluation
Authors: Zoëga S. , Gunnarsdóttir S. , Gordon D.B. 
Published: July 2014

Abstract

Aims
To gain an understanding of the concept of quality pain management (QPM) in the hospital setting, and to define the concept.

Methods
A concept evaluation based on the method by Morse and colleagues was done. The literature was searched according to selected key words in five databases. Over 5000 articles were found but data were limited to 37 articles directly related to both quality and pain management in adults in the hospital setting, and published in peer-reviewed journals or by an official organization. Data were extracted from these articles and then synthesized according to definition, characteristics, boundaries, preconditions, and outcomes of QPM.

Results
QPM is a multidimensional concept that is commonly used but remains vaguely defined. A common understanding of the concept is nonetheless evident in the literature. QPM refers to the structure, process, and outcomes of care rooted in equitable, effective, patient-centered, safe, and efficient services. The structure encompasses competent staff and staff accountability, organizationally supported evidence-based policies, and access to interprofessional and specialized care. The process consists of screening, assessing and reassessing pain, individualized and evidence-based treatment, communication of pain and pain treatment, and patient and family education. Finally, outcomes include increase in patient satisfaction, reduced pain severity, less functional interferences, and decrease in both prevalence and severity of adverse effects from pain or its treatment.

Conclusions
QPM is a complex concept that despite common use lacks a clear definition. The relationship between structure, process, and outcome needs to be studied in order to improve QPM. The conceptual model put forward in this study needs to be further refined and tested.
Aligning conservation and research priorities for proactive species and habitat management: the case of dugongsDugong dugonin Johor, Malaysia
Authors: Ponnampalam Louisa S. , Fairul Izmal J. H. , Adulyanukosol Kanjana , Ooi Jillian L. S. , Reynolds John E. 
Published: July 2014

AbstractConservation efforts use scientific data to provide an adaptive framework wherein habitat and wildlife sustainability can co-exist with human activities. Good science informs decision-makers and facilitates the development of successful conservation approaches. However, conservation concerns for the dugongDugong dugonin South-east Asia are sufficiently urgent that action must be taken quickly, even though science has not provided complete answers to critical questions. In Johor, Malaysia, aerial surveys were conducted to assess dugong numbers, dugong high-use areas and overlap of dugong sightings with areas of seagrass. Dugong distribution included existing marine parks and locations where known conservation threats exist. We conclude that the Johor islands may represent a significant congregation site for dugongs in Peninsular Malaysia, with as many as 20 dugongs recorded in a single day. The existence of a marine park where the dugong sightings were most prominent is encouraging but only 38% of those sightings fell within the boundaries of the park. Anthropogenic threats need to be assessed and addressed prior to complex development activities such as dredging and coastal reclamation for tourism development in this critical area. We use this case to explore the concept of advancing species conservation through focused research and management, particularly where uncertainties exist because data are scarce.
Resistance to niclosamide in Oncomelania hupensis, the intermediate host of Schistosoma japonicum: should we be worried?
Authors: DAI JIAN-RONG , LI YOU-ZI , WANG WEI , XING YUN-TIAN , QU GUO-LI , LIANG YOU-SHENG 
Published: July 2014

SUMMARYAs the currently only available molluscicide, niclosamide has been widely used for snail control for over 2 decades in China. There is therefore a concern about the emergence of niclosamide-resistant snail populations following repeated, extensive use of the chemical. The purpose of this study was to investigate the likelihood of niclosamide resistance in Oncomelania hupensis in China. Active adult O. hupensis snails derived from 20 counties of 10 schistosomiasis-endemic provinces of China, of 10 snails in each drug concentration, were immersed in solutions of 1, 0·5, 0·25, 0·125, 0·063, 0·032, 0·016 and 0·008 mg L−1 of a 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25 °C, and the median lethal concentration (LC50) was estimated. Then, the 24- and 48-h WPN LC50 values were compared with those determined in the same sampling sites in 2002. The results indicated that the 24- and 48-h WPN LC50 values for O. hupensis were not significantly different from those determined in 2002 (P = 0·202 and 0·796, respectively). It is concluded that the current sensitivity of O. hupensis to niclosamide has not changed after more than 2 decades of repeated, extensive application in the main endemic foci of China, and there is no evidence of resistance to niclosamide detected in O. hupensis.
Perceptions of a patient-staff-caregiver group among inpatients in a radiotherapy unit
Authors: Mitnik Inbal , Zalman Daniela , Vorobeichik Marina , Gurevich-Halevi Michal , Eliasov Liron , Lulav-Grinwald Doron , Bar-Sela Gil 
Published: July 2014

AbstractObjective:Coping with cancer and its treatments has significant psychological implications for patients, and hospitalization can lead to emotional distress. Based on a community meeting (CM), a common therapeutic intervention in psychiatric wards, a unique patient–staff–caregiver group is held weekly on the radiotherapy unit of our hospital. The goals are to strengthen patient coping abilities and prompt open communications. The present study aimed at quantitatively estimating the effect of the community meeting by gauging the perceptions with respect to several therapeutic aspects.Method:A questionnaire was developed for patients who participated in CMs during their hospitalization based on four theoretical factors: illness perception, relations with the main caregiver, relations with other participants, and relations with unit staff.Results:Participants' general satisfaction with the meetings was found to be positive. The most significant aspect of the meetings, as perceived by participants, was relationships with the staff. Patients born in Israel perceived relationships with other participants more positively.Significance of results:Attentive interaction with medical staff and open communications are highly important for patients and contribute to their general satisfaction with the meetings.
Irrational exuberance and neural crash warning signals during endogenous experimental market bubbles
Authors: Smith Alec , Lohrenz Terry , King Justin , Montague P. Read , Camerer Colin F. 
Published: July 2014

Significance
Asset price bubbles are an important example of human group decision making gone awry, but the behavioral and neural underpinnings of bubble dynamics remain mysterious. In multisubject markets determined by 11–23 subjects, with 2–3 subjects simultaneously scanned using functional MRI, we show how behavior and brain activity interact during bubbles. Nucleus accumbens (NAcc) activity tracks the price bubble and predicts future price changes. Traders who buy more aggressively based on NAcc signals earn less. High-earning traders have early warning signals in the anterior insular cortex before prices reach a peak, and sell coincidently with that signal, precipitating the crash. These experiments could help understand other cases in which human groups badly miscompute the value of actions or events.
Improving management of small natural features on private lands by negotiating the science–policy boundary for Maine vernal pools
Authors: Calhoun Aram J. K. , Jansujwicz Jessica S. , Bell Kathleen P. , Hunter Malcolm L. 
Published: July 2014

SignificanceWe address a key sustainability challenge: management of natural resources on private land. Managing small natural features, such as vernal pools, on private land presents unique problems but also unique opportunities to provide benefits to both nature and society. Our innovative approach to management and research described here uses vernal pools as a model system but exemplifies a broader framework for understanding social and ecosystem processes, interactions between them, and how these interactions may facilitate solutions. The challenges and opportunities encountered in navigating the science–policy boundary presented here are not unique to vernal pools: Our findings have wider conservation significance for natural resource management, especially for other small natural features on private lands (e.g., riparian zones, prairie potholes).
Effect of sleep deprivation on the human metabolome
Authors: Davies Sarah K. , Ang Joo Ern , Revell Victoria L. , Holmes Ben , Mann Anuska , Robertson Francesca P. , Cui Nanyi , Middleton Benita , Ackermann Katrin , Kayser Manfred , Thumser Alfred E. , Raynaud Florence I. , Skene Debra J. 
Published: July 2014

Significance
Sleep restriction and circadian clock disruption are associated with metabolic disorders including obesity and diabetes; this association can be studied by using the powerful tool of metabolomics. By using liquid chromatography/MS metabolomics, we have characterized plasma metabolites that were significantly affected by acute sleep deprivation (mainly lipids and acylcarnitines), all increasing during sleep deprivation. Observed increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of sleep deprivation and deserve further study. Clear daily rhythms were observed in most metabolites, with 24 h wakefulness mainly reducing the amplitude of these rhythms. Our results further the understanding of sleep/wake regulation and the associated metabolic processes, and will be vital when using metabolic profiling to identify robust biomarkers for disease states and drug efficacy.
Mechanisms underlying the activation of G-protein–gated inwardly rectifying K+(GIRK) channels by the novel anxiolytic drug, ML297
Authors: Wydeven Nicole , Marron Fernandez de Velasco Ezequiel , Du Yu , Benneyworth Michael A. , Hearing Matthew C. , Fischer Rachel A. , Thomas Mark John , Weaver C. David , Wickman Kevin 
Published: July 2014

SignificanceMany neurotransmitters dampen excitability in the heart and brain by activating G-protein–gated inwardly rectifying K+(GIRK) channels. The lack of selective pharmacological tools for GIRK channels has hindered investigations into their physiological and pathophysiological relevance. Here, we examined the mechanisms underlying the activation of GIRK channels by ML297, the prototypical member of a new family of small molecule GIRK channel modulators. ML297 activates GIRK channels via a unique mechanism that requires two amino acids specific to the GIRK1 subunit. In addition, ML297 reduces anxiety-related behavior in mice, in a GIRK1-dependent manner, without triggering sedation or addiction-related behavior. Thus, ML297 is a new tool for probing the therapeutic potential of GIRK channel modulation, which may benefit individuals with anxiety-related disorders.
Detouring of cisplatin to access mitochondrial genome for overcoming resistance
Authors: Marrache Sean , Pathak Rakesh K. , Dhar Shanta 
Published: July 2014

Significance
Resistance of aggressive metastatic tumors to cisplatin therapy is partly related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair machinery. Delivering cisplatin to the mitochondria to attack the mitochondrial genome lacking such repair machinery can lead to a rationally designed therapy for metastatic, chemoresistant cancers and might overcome the problems associated with conventional cisplatin treatment.
Genetically Improved Crops
Authors: Newell-McGloughlin Martina 
Published: July 2014

AbstractThis article focuses on the technological challenges in developing biotechnology and nutritionally enhanced crops. It discusses how the lack of basic knowledge about plant metabolism has hindered research on improving the nutritional quality of plants. It describes new technologies that seek to counter some of the complex problems in the metabolic engineering of pathways, overcome the limitation of single gene transfers, and facilitate the concomitant transfer of multiple components of metabolic pathways. Sample applications of these technologies are also discussed.
Mathematics Learning in the USA and JAPAN
Authors: Okamoto Yukari 
Published: July 2014

AbstractThis chapter examines the idea that spoken language of mathematics could be a potential factor in explaining variation in mathematics achievement between East Asian and US students. A particular focus was placed on the number naming systems of East Asian languages that are rooted in ancient Chinese. In these languages, the organization of number names follows the rules of the base-ten system. Studies that examined influences of number naming systems on children’s mathematical competence showed that young children speaking East Asian languages prefer to represent two-digit numbers as consisting of tens and ones. Although these results seem limited to specific mathematical competence, it is argued that strong foundations built around base-ten knowledge are likely to contribute to later mathematics performance. Some disadvantages of East Asian languages are also discussed.
Communication Modalities and Political Knowledge
Authors: Eveland William P. , Garrett R. Kelly 
Published: July 2014

Abstract
Recent research has made clear that the process by which individuals obtain information about politics through the media and other communication sources is complex and multifaceted. The effects of communication on knowledge can vary by medium or the mix of sources that individuals choose, by the motivations and background characteristics of the user, and by the type of knowledge being considered. Whether “knowledge” (as opposed to misperceptions or simply beliefs) is the end result of communication depends crucially on the nature of the information being presented and the prior beliefs of the user. The authors review the state of the art research in this domain and offer suggestions for how scholarship must adjust to the changing environment brought about by technological change and increasing partisanship and polarization among politicians, the media, and the public.
Political Communication
Authors: Green Donald P. , Carnegie Allison J. , Middleton Joel 
Published: July 2014

Abstract
In an effort to overcome the limitations of survey research and lab experimentation, researchers studying the effects of communication have increasingly turned to field experimentation, or randomized trials conducted in real-world settings. This essay describes the research designs and findings from illustrative field experiments in three substantive domains. First, the authors consider public information campaigns designed to encourage voters to hold public officials accountable for performance in office. Second, they discuss individually targeted information designed to encourage voters and taxpayers to comply with social norms. Finally, they review recent attempts to study the electoral effects of television and radio advertisements. This array of studies illustrates how field experiments may contribute to a broad range of important theoretical and policy debates.
Emergence of Higher Cognitive Functions
Authors: Paz-Alonso Pedro M. , Bunge Silvia A. , Ghetti Simona 
Published: July 2014

Abstract
In the present chapter, we first provide an overview of neurodevelopmental changes in brain structure and function, which have implications for the development of higher cognitive functions as well as for other areas of research within developmental cognitive neuroscience. Second, we highlight neuroimaging evidence regarding the development of working memory and cognitive control processes, and the main neural mechanisms and brain networks supporting them. Third, we review behavioral and neuroimaging research on the development of memory encoding and retrieval processes, including episodic memory and mnemonic control. Finally, we summarize important current and future directions in the study of the neurocognitive mechanisms supporting the development of higher cognitive functions, noting that multidisciplinary approaches, different level of analyses, and longitudinal designs are needed to shed further light on the emergence and trajectories of these functions over development.
Acute Leukemia Presenting as Acute Hepatitis Without Liver Failure
Authors: Rivet Christine , Leverger Guy , Jacquemin Emmanuel , Bernard Olivier 
Published: July 2014

ABSTRACTA diagnosis of acute lymphoblastic or myeloblastic leukemia was made in 6 children ages 4 to 14 years who presented with a clinicobiochemical picture of acute hepatitis without liver failure. Standard chemotherapy, including 1 week pretreatment with steroids in children with lymphoblastic leukemia, allowed complete remission of the leukemia and normalization of serum liver tests.
Cardiac alternans and intracellular calcium cycling
Authors: Edwards Joshua N , Blatter Lothar A 
Published: July 2014

SummaryCardiac alternans refers to a condition in which there is a periodic beat‐to‐beat oscillation in electrical activity and the strength of cardiac muscle contraction at a constant heart rate. Clinically, cardiac alternans occurs in settings that are typical for cardiac arrhythmias and has been causally linked to these conditions. At the cellular level, alternans is defined as beat‐to‐beat alternations in contraction amplitude (mechanical alternans), action potential duration (APD; electrical or APD alternans) and Ca2+ transient amplitude (Ca2+ alternans). The cause of alternans is multifactorial; however, alternans always originate from disturbances of the bidirectional coupling between membrane voltage (Vm) and intracellular calcium ([Ca2+]i). Bidirectional coupling refers to the fact that, in cardiac cells, Vm depolarization and the generation of action potentials cause the elevation of [Ca2+]i that is required for contraction (a process referred to as excitation–contraction coupling); conversely, changes of [Ca2+]i control Vm because important membrane currents are Ca2+ dependent. Evidence is mounting that alternans is ultimately caused by disturbances of cellular Ca2+ signalling. Herein we review how two key factors of cardiac cellular Ca2+ cycling, namely the release of Ca2+ from internal stores and the capability of clearing the cytosol from Ca2+ after each beat, determine the conditions under which alternans occurs. The contributions from key Ca2+‐handling proteins (i.e. surface membrane channels, ion pumps and transporters and internal Ca2+ release channels) are discussed.
Effects of milk replacer and starter diet provided as creep feed for suckling pigs on pre‐ and post‐weaning growth
Authors: Park Byung‐Chul , Ha Duck‐Min , Park Man‐Jong , Lee Chul Young 
Published: July 2014

AbstractThis study was aimed at investigating the long‐term effects of provision of liquid milk replacer (MR) and solid starter diet (SD) during lactation on post‐weaning (PW) growth of pigs. In experiment 1, 33 cross‐bred litters were allotted to four treatments: no supplement (CON), MR ad libitum, SD ad libitum and 100 g SD/litter/day from lactation day 4 through weaning at day 21 during late fall. In experiment 2, 40 litters received MR or none in July. PW pigs received commercial diets to marketing. In experiment 1, weaning weight (WW), pre‐weaning average daily gain (ADG) and mortality (2.4%) were not influenced by creep‐feeding MR or SD. ADG was greater (P < 0.05) in the MR group versus CON during days 21–54, but did not differ across the treatments during days 54–162. In experiment 2, ADG during lactation and WW were greater in the MR group versus CON, with mortality lower in the former (5.6 vs. 10.3%). However, PW ADG to day 175 did not differ between the two groups. Results suggest that creep‐feeding MR or SD has no effect on PW growth. However, it remains possible that MR reduces PW mortality during the hot season.