bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lenalidomide at Therapeutic and Supratherapeutic Doses Does Not Prolong QTc Intervals in the Thorough QTc Study Conducted in Healthy Men
Authors: Chen Nianhang , Ye Ying , Liu Liangang , Reyes Josephine , Assaf Mahmoud S. , Kasserra Claudia , Zhou Simon , Palmisano Maria 
Published: May 2013

AbstractThe effect of lenalidomide on the corrected QT (QTc) interval was evaluated in healthy men and extended to patients based on the lenalidomide concentration–QTc (C–QTc) relationship. A rigorous assessment of the effect of lenalidomide on QTc intervals was conducted in healthy volunteers who each received, in randomized order, a single oral dose of 10 mg lenalidomide, 50 mg lenalidomide, 400 mg moxifloxacin (positive control) and placebo. Plasma lenalidomide exposure was compared between healthy volunteers and patients with multiple myeloma or myelodysplastic syndromes. In healthy volunteers, moxifloxacin produced the expected significant prolongation in QTcI (individual correction). For lenalidomide 10 mg and 50 mg, the time‐matched changes from placebo in the baseline‐adjusted least‐squares mean QTcI were <3 ms with the upper limit of the two‐sided 90% confidence interval for the change <10 ms at all time‐points. No subjects experienced QTcI >450 ms or change from baseline >60 ms after lenalidomide administration. Similar results were seen with QT interval data corrected by Fridericia and Bazett methods. The C–QTc analysis yielded no significant association between lenalidomide concentrations and QTcI changes up to 1522 ng/mL; this range was close to that observed in patients receiving lenalidomide doses up to 50 mg, including those with reduced drug clearance due to renal impairment. In conclusion, single doses of lenalidomide up to 50 mg were not associated with prolonged QTc intervals in healthy males. The C–QTc analysis further assured that lenalidomide doses up to 50 mg are not expected to prolong QTc intervals in patients.
Losartan protects liver against ischaemia/reperfusion injury through PPAR‐γ activation and receptor for advanced glycation end‐products down‐regulation
Authors: Koh Eun‐Ji , Yoon Seong‐Jin , Lee Sun‐Mee 
Published: May 2013

Background and PurposePPAR‐γ has been reported to be a protective regulator in ischaemia/reperfusion (I/R) injury. The receptor for advanced glycation end‐products (RAGE) plays a major role in the innate immune response, and its expression is associated with PPAR‐γ activation. Several angiotensin receptor blockers possess partial agonist activities towards PPAR‐γ. Therefore, this study investigated the action of losartan, particularly with regard to PPAR‐γ activation and RAGE signalling pathways during hepatic I/R.Experimental ApproachMice were subjected to 60 min of ischaemia followed by 6 h of reperfusion. Losartan (0.1, 1, 3 and 10 mg·kg−1) was administered 1 h prior to ischaemia and immediately before reperfusion. GW9662, a PPAR‐γ antagonist, was administered 30 min prior to first pretreatment with losartan.Key ResultsLosartan enhanced the DNA‐binding activity of PPAR‐γ in I/R. Losartan attenuated the increased serum alanine aminotransferase activity, TNF‐α and IL‐6 levels, and nuclear concentrations of NF‐κB in I/R. GW9662 reversed these beneficial effects. Losartan caused a decrease in apoptosis as assessed by TUNEL assay, in release of cytochrome c and in cleavage of caspase‐3, and these effects were abolished by GW9662 administration. Losartan attenuated not only I/R‐induced RAGE overexpression, but also its downstream early growth response protein‐1‐dependent macrophage inflammatory protein 2 level; phosphorylation of p38, ERK and JNK; and subsequent c‐Jun phosphorylation. GW9662 reversed these effects of losartan administration.Conclusions and ImplicationsOur findings suggest that losartan ameliorates I/R‐induced liver damage through PPAR‐γ activation and down‐regulation of the RAGE signalling pathway.
Improvement of aortic valve stenosis by ApoA‐I mimetic therapy is associated with decreased aortic root and valve remodelling in mice
Authors: Trapeaux J , Busseuil D , Shi Y , Nobari S , Shustik D , Mecteau M , El‐Hamamsy I , Lebel M , Mongrain R , Rhéaume E , Tardif J‐C 
Published: May 2013

Background and PurposeWe have shown that infusions of apolipoprotein A‐I (ApoA‐I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA‐I mimetic therapy in mice with calcific or fibrotic AVS.Experimental ApproachApolipoprotein E‐deficient (ApoE−/−) mice and mice with Werner progeria gene deletion (WrnΔhel/Δhel) received high‐fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA‐I mimetic peptide infusions (ApoA‐I treated groups, 100 mg·kg−1 for ApoE−/− mice; 50 mg·kg−1 for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology.Key ResultsAortic valve area (AVA) increased in both ApoE−/− and Wrn mice treated with the ApoA‐I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA‐I treated ApoE−/− mice. The type I/III collagen ratio was lower in the sinus wall of ApoA‐I treated ApoE−/− mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA‐I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA.Conclusions and ImplicationsApoA‐I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice.
A review of the global literature on dental therapists
Authors: Nash David A. , Friedman Jay W. , Mathu‐Muju Kavita R. , Robinson Peter G. , Satur Julie , Moffat Susan , Kardos Rosemary , Lo Edward C.M. , Wong Anthony H.H. , Jaafar Nasruddin , van den Heuvel Jos , Phantumvanit Prathip , Chu Eu Oy , Naidu Rahul , Naidoo Lesley , McKenzie Irving , Fernando Eshani 
Published: May 2013

AbstractObjectiveAccess to adequate oral health care is deficient in many parts of the world. Many countries are now using dental therapists to increase access, particularly for children. To inform the discussion on dental therapists in the workforce, particularly in the United States, the W.K. Kellogg Foundation funded a review of the global literature to identify as many documents as possible related to the practice of dental therapists since the establishment of the School Dental Service in New Zealand in 1921.MethodsConsultants in each of the countries considered to have a substantive literature on dental therapists were asked to participate in the research; seventeen in total. In addition to identifying and reviewing published articles, a focus of the research was on identifying ‘gray’ documents. Standard databases were searched for key words associated with dental therapists. In addition, searches were conducted of the governmental and dental association websites of all countries known to have dental therapists in their oral health workforce.ResultsFifty‐four countries, both developing and developed, were identified where dental therapists are members of the workforce. Eleven hundred documents were identified from 26 of these countries, with over 2/3 of them cited in the published monograph. Reliable evidence from the related literature and verbal communication confirmed the utilization of dental therapists in an additional 28 countries. Thirty‐three of the countries were members of the Commonwealth of Nations, suggesting a mechanism of spread from New Zealand.Variable lengths of training/education existed for dental therapists with the tradition being 2 years postsecondary. In a few countries, the training of therapists and hygienists is now being combined in a three academic year program. Historically, dental therapists have been employed by government agencies caring for children, typically in school‐based programs. Initiatives in some countries allow limited care for adults by dental therapists with additional training.ConclusionsThe evidence indicates that dental therapists provide effective, quality, and safe care for children in an economical manner and are generally accepted both by the public and where their use is established, by the dental profession.
The extremely resorbed mandible, 10‐year results of a randomized controlled trial on 3 treatment strategies
Authors: Stellingsma Kees , Raghoebar Gerry M. , Visser Anita , Vissink Arjan , Meijer Henny J. A. 
Published: May 2013

AbstractObjectivesTo prospectively compare the clinical and radiographic results of three modes of implant treatment for implant‐retained mandibular overdentures in patients with extremely resorbed mandibles. The three treatment strategies used were (1) a transmandibular implant, (2) augmentation of the mandible with an autologous bone graft followed by placement of four endosseous implants, and (3) placement of four short endosseous implants.Materials and methodsSixty edentulous patients met the inclusion criteria and were assigned according to a balanced allocation method to 1 of the 3 treatment strategies. Implant survival, surgical retreatment rates, and peri‐implant bone loss were assessed according to a standardized protocol during a 10‐year evaluation period.ResultsDuring the evaluation period, significantly more implants were lost in the transmandibular implant (cumulative 10‐year implant survival rate, 76.3%) and the augmentation groups (88%) compared to the group provided with short endosseous implants (98.8%). The 10‐year retreatment rate was significantly more favorable in the endosseous implants only (0%) and augmentation groups (5%) compared to the transmandibular group (30%). In all three groups, there was minor peri‐implant bone loss.DiscussionAlthough implant loss is a frequently used outcome measure for success, the necessity of surgical retreatment seems to be of more relevance for both the patient and the clinician.ConclusionConsidering the favorable clinical and radiographic parameters and the fact that patients can be treated in outdoor clinic setting, the use of short endosseous implants in combination with an overdenture is the first choice of treatment in patients with extremely resorbed mandibles.
A longitudinal study of dental arch morphology in children with the syndrome of Crouzon or Apert
Authors: Reitsma Jacobus H. , Elmi Poejan , Ongkosuwito Edwin M. , Buschang Peter H. , Prahl‐Andersen Birte 
Published: May 2013

The aim of this study was to compare changes in dental arch morphology between patients with Crouzon syndrome or Apert syndrome and controls. Children between 4 and 14 yr of age with Crouzon syndrome (n = 40) or Apert syndrome (n = 28) were compared with non‐syndromic controls (n = 457) in terms of arch widths, depths, and length dimensions. Multilevel statistical modeling techniques were used to evaluate changes over time. Dental arch dimensions were found to be smaller in patients with Crouzon syndrome or Apert syndrome compared with control subjects. Maxillary intercanine width for patients with Apert syndrome were increased, whilst other arch width variables showed no change. Patients with Crouzon syndrome showed increases in maxillary intercanine width, whilst intermolar width showed no change over time. Dental arch dimensions in syndromic patients were thus found to be consistently smaller than in control subjects between 4 and 14 yr of age, implying that patients with Crouzon syndrome and Apert syndrome had a diminished growth potential.
Definition of drug‐resistant epilepsy: Is it evidence based?
Authors: Wiebe Samuel 
Published: May 2013

SummaryClinical case definitions are the cornerstone of clinical communication and of clinical and epidemiologic research. The ramifications of establishing a case definition are extensive, including potentially large changes in epidemiologic estimates of frequency, and decisions for clinical management. Yet, defining a condition entails numerous challenges such as defining the scope and purpose, incorporating the strongest evidence base with clinical expertise, accounting for patients' values, and considering impact on care. The clinical case definition of drug‐resistant epilepsy, in addition, must address what constitutes an adequate intervention for an individual drug, what are the outcomes of relevance, what period of observation is sufficient to determine success or failure, how many medications should be tried, whether seizure frequency should play a role, and what is the role of side effects and tolerability. On the other hand, the principles of evidence‐based medicine (EBM) aim at providing a systematic approach to incorporating the best available evidence into the process of clinical decision for individual patients. The case definition of drug‐resistant epilepsy proposed by the the International League Against Epilepsy (ILAE) in 2009 is evaluated in terms of the principles of EBM as well as the stated goals of the authors of the definition.
Epilepsy informatics and an ontology‐driven infrastructure for large database research and patient care in epilepsy
Authors: Sahoo Satya S. , Zhang Guo‐Qiang , Lhatoo Samden D. 
Published: May 2013

SummaryThe epilepsy community increasingly recognizes the need for a modern classification system that can also be easily integrated with effective informatics tools. The 2010 reports by the United States President's Council of Advisors on Science and Technology (PCAST) identified informatics as a critical resource to improve quality of patient care, drive clinical research, and reduce the cost of health services. An effective informatics infrastructure for epilepsy, which is underpinned by a formal knowledge model or ontology, can leverage an ever increasing amount of multimodal data to improve (1) clinical decision support, (2) access to information for patients and their families, (3) easier data sharing, and (4) accelerate secondary use of clinical data. Modeling the recommendations of the International League Against Epilepsy (ILAE) classification system in the form of an epilepsy domain ontology is essential for consistent use of terminology in a variety of applications, including electronic health records systems and clinical applications. In this review, we discuss the data management issues in epilepsy and explore the benefits of an ontology‐driven informatics infrastructure and its role in adoption of a “data‐driven” paradigm in epilepsy research.
Ratcheting assessment of materials based on the modified Armstrong–Frederick hardening rule at various uniaxial stress levels
Authors: Ahmadzadeh G. R. , Varvani‐Farahani A. 
Published: May 2013

ABSTRACTThe present study evaluates ratcheting response of materials by means of the Armstrong–Frederick (A–F) hardening rule, the modified A–F rule (Bower's model), and further modifications of the hardening rule based on new introduced coefficients. The implemented modifications on the A–F‐based hardening rule aims to address stages of ratcheting over stress cycles. The modified hardening rule predicts the ratcheting strain rate decay over stage I and the constant rate of strain accumulation during stage II. The modified hardening rule consisted of the coefficients of the hardening rule controlling stress–strain hysteresis loops generated over stress cycles during ratcheting process (Bower's modification on A–F rule) plus the coefficients controlling rates over stages of materials ratcheting deformation. Stress–strain‐dependent coefficients in the modified rule are responsible to compromise overprediction of ratcheting of A–F during stage I and the premature plastic shakedown beyond stage I induced by Bower's model. Ratcheting strain rate coefficients improved the hardening rule capability to calibrate and control the rate of ratcheting in stages I and II and enabled the modified hardening rule to predict ratcheting strain over a prolonged domain of stress cycles. The modified hardening rule was employed to assess ratcheting response of 304, 42CrMo, 316L steel and copper samples under uniaxial loading conditions. The predicted ratcheting values based on the modified hardening rule and the experimental ratcheting strains were found in good agreements.
Effect of leaf litter characteristics on leaf conditioning and on consumption by Gammarus pulex
Authors: Foucreau Natacha , Puijalon Sara , Hervant Frédéric , Piscart Christophe 
Published: May 2013

Summary

Terrestrial leaf litter inputs provide an essential energy source for many freshwater organisms. Processing of leaf litter involves several physicochemical and biological factors but always starts with the colonisation of leaves by aquatic hyphomycetes.

Here, we document changes occurring on leaf tissues of three tree species, alder, hornbeam and oak, with contrasted leaf properties. Changes in the mechanical properties of leaves and in fungal growth were followed at 10, 25, 35, 45 and 55 days of immersion in natural winter conditions. We hypothesised that fungal growth will be faster and mechanical characteristics will decrease more rapidly in softer, nutrient‐rich, than in tougher leaves. In addition, we tested whether the consumption rate of conditioned leaves by the amphipod shredder Gammarus pulex was correlated with the mechanical properties of leaves and their ergosterol content (as a proxy for fungal biomass).

Leaf toughness decreased (with different rates for the 3 litter species), whereas the leaf thickness remained stable. The mechanical properties of alder and hornbeam leaves changed similarly, in contrast to oak leaves. Ergosterol contents increased over time more rapidly for alder and hornbeam than for oak leaves for which the fungal growth was delayed. Ergosterol content, leaf toughness and leaf consumption rates by G. pulex were significantly correlated. Leaf consumption rates by G. pulex were higher for soft than for tough leaves.

Our results suggest that the consumption of different types of leaves may be delayed according to the time required to acquire conditioning sufficient for shredder consumption. The presence of tough leaves in riparian vegetation may constitute a reservoir of trophic resources available for aquatic organisms at the end of the winter, when soft leaves have been entirely consumed. The diversity of riparian vegetation may hence contribute to sustaining the availability of food resources for adjacent aquatic ecosystems.
A comparison of shot‐encoding schemes for wave‐equation migration
Authors: Godwin Jeff , Sava Paul 
Published: May 2013

ABSTRACTIn the last decade the seismic imaging industry has begun collecting data volumes with a substantial amount of data redundancy through new acquisition geometries including: wide‐azimuth, rich‐azimuth and full‐azimuth geometries. The increased redundancy significantly improves image quality in areas with complex geology, but requires considerably greater computational power to construct an image because of the additional data and the need to use advanced imaging algorithms. One way to reduce the computational cost of processing such datasets is to blend shot‐records, using shot‐encoding, together prior to imaging which reduces the number of migrations necessary for imaging. The downside to doing so is that blending introduces strong, non‐physical, cross‐talk noise into the final image. By carefully choosing the shot‐encoding scheme, we can reduce the additional noise inserted into the image and maximally reduce the number of migrations necessary. We describe a theory of blended imaging that explains all shot‐encoding schemes, and use the theory to design a new class of encodings that use amplitude weights instead of phase‐shifts or time‐delays. We are able to use amplitude encoding to produce blended images of the same quality as previous encoding schemes at a similiar computational cost. Furthermore, we compare the results of amplitude encoding with the results from well‐known shot‐encoding schemes from previous work including: plane‐wave migration, random‐time delay, modulated‐shot migration, and decimated shot‐record migration. In our comparison, we find that plane‐wave migration is in many ways an optimal shot‐encoding scheme. However, we find that plane‐wave migration produces results that are comparable to decimated shot‐record migration when the total cost of imaging is taken into account, thereby calling into question the utility of shot‐encoding in general. Overall, this work questions the potential for shot‐encoding in standard (shot‐record) seismic imaging because blended imaging does not appear to sufficiently reduce the cost of imaging given the quality of the blended image compared to decimated shot‐record migration.
Attitudes toward seeking medical care: development and standardization of a comprehensive scale
Authors: Fischer Edward H. , Dornelas Ellen A. , DiLorenzo Terry A. 
Published: May 2013

AbstractA scale measuring attitudes toward seeking medical help was devised and pretested with college students. The scale was internally consistent and had evident factorial and congruent validity. In a second sample, both the revised scale and its primary attitudinal component—an action–intention subscale—had strong test–retest reliability and correlation with reported medical appointments and contacts assessed approximately 2 months later. In a sample of Hartford, CT residents, the scale's factorial structure was remarkably similar to that of the students. Help‐seeking attitudes differentiated between people who had been treated for a medical crisis and those who had not; those with and without health insurance; and, of the insured, those who considered their coverage adequate and those who did not.
Systematic review of instruments measuring homophobia and related constructs
Authors: Costa Angelo Brandelli , Bandeira Denise Ruschel , Nardi Henrique Caetano 
Published: May 2013

AbstractSince its conceptualization, the construct of homophobia has been the subject of many speculations about its specificity, reach, and possibility of empirical assessment. Several instruments have been created aiming to measure the prejudice against homosexuals. Peer‐reviewed articles of studies using measures to assess homophobia and related constructs were systematically reviewed in 4 databases (Medline, PsycINFO, ERIC, JSTOR). The articles were classified as they displayed evidence of the instrument's validity, reliability, or both. Finally, the instruments were rated according to that evidence. Out of 1076 results, 115 studies between 1993 and 2010 were identified as relevant. Those studies used 47 different instruments. This review focused in 5 instruments that concentrated the majority of the citations. Psychometric properties were acceptable.