bluuebunny/crossref_metadata_2025_split huggingface dataset:
New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications
Authors: FENGER‐ERIKSEN C. , MÜNSTER A.‐M. , GROVE E. L. 
Published: April 2014

New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa‐inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents.This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.
Redundancy in seed dispersal by three sympatric ungulates: a reintroduction perspective
Authors: Polak T. , Gutterman Y. , Hoffman I. , Saltz D. 
Published: April 2014

AbstractReintroductions may play an important role in re‐establishing key ecosystem functions and are potentially a valuable ecosystem‐restoration tool. Here, we focus on the role of reintroduced ungulates as seeds dispersers – a key process in shaping plant community structure and dynamics. In a comparative study, we investigated which plant species are dispersed by three sympatric ungulates in the Negev desert, Israel: Arabian oryx Oryx leucoryx, Asiatic wild ass Equus hemionus and dorcas gazelle Gazella dorcas. The oryx and wild ass were locally extirpated and recently reintroduced while the gazelle is the only wide‐ranging ungulate that has existed continuously in the region. We hypothesized that although all three species are ungulates, because of expected differences in diet resulting from the differences in their size and digestive characteristics, there will be little overlap in their role as seed dispersers. In addition, we experimentally tested the importance of ingestion of the seeds of the keystone acacia Acacia raddiana and the presence of dung on germination success and seedlings growth. We found that each of the ungulates dispersed a different assemblage of plant species with little overlap, highlighting the importance of the reintroduction of both species in ecosystem restoration. Oryx were the key dispersers of acacia seeds, and oryx‐ingested seeds planted with oryx pellets had a germination success 250 times higher than non‐ingested seeds planted without pellets. Seedlings from ingested seeds also grew faster than seedlings from non‐ingested seeds. We found little redundancy between ungulates as seed dispersers in this region, highlighting the importance of reintroductions as a restorative process even when other species from the same guild still exist in the wild.
Non‐Human Primate Models of Hormonal Contraception and HIV
Authors: McNicholl Janet M. , Henning Tara C. , Vishwanathan Sundaram A. , Kersh Ellen N. 
Published: April 2014

ProblemRecent concerns that hormonal contraception (HC) may increase risk of HIV acquisition has led to keen interest in using non‐human primates (NHP) to understand the underlying mechanism and the magnitude of the risk. This is, in part, because some experiments which would be difficult or logistically impossible in women are more easily conducted in NHP.Method of studyNHP models of HIV can inform HIV acquisition and pathogenesis research and identify and evaluate biomedical preventions and treatments for HIV/AIDS. Widely used species include rhesus, pigtail, and cynomolgous macaques.ResultsThis paper reviews past, current and proposed NHP research around the intersection of HIV and HC.ConclusionNHP research may lead to the identification of hormonally regulated biomarkers that correlate with HIV‐acquisition risk, to a ranking of existing or next‐generation HC along an HIV‐acquisition risk profile, and inform research around new biomedical preventions for HIV.
Analysis of transthoracic echocardiographic data in major vascular surgery from a prospective randomised trial comparing sevoflurane and fentanyl with propofol and remifentanil anaesthesia
Authors: Lindholm E. E. , Aune E. , Frøland G. , Kirkebøen K. A. , Otterstad J. E. 
Published: April 2014

SummaryThe aim of this study was to define pre‐operative echocardiographic data and explore if postoperative indices of cardiac function after open abdominal aortic surgery were affected by the anaesthetic regimen. We hypothesised that volatile anaesthesia would improve indices of cardiac function compared with total intravenous anaesthesia. Transthoracic echocardiography was performed pre‐operatively in 78 patients randomly assigned to volatile anaesthesia and 76 to total intravenous anaesthesia, and compared with postoperative data. Pre‐operatively, 16 patients (10%) had left ventricular ejection fraction < 46%. In 138 patients with normal left ventricular ejection fraction, 5/8 (62%) with left ventricular dilatation and 41/130 (33%) without left ventricular dilatation had evidence of left ventricular diastolic dysfunction (p < 0.001). Compared with pre‐operative findings, significant increases in left ventricular end‐diastolic volume, left atrial maximal volume, cardiac output, velocity of early mitral flow and early myocardial relaxation occurred postoperatively (all p < 0.001). The ratio of the velocity of early mitral flow to early myocardial relaxation remained unchanged. There were no significant differences in postoperative echocardiographic findings between patients anaesthetised with volatile anaesthesia or total intravenous anaesthesia. Patients had an iatrogenic surplus of approximately 4.1 l of fluid volume by the first postoperative day. N‐terminal prohormone of brain natriuretic peptide increased on the first postoperative day (p < 0.001) and remained elevated after 30 days (p < 0.001) in both groups. Although postoperative echocardiographic alterations were most likely to be related to increased preload due to a substantial iatrogenic surplus of fluid, a component of peri‐operative myocardial ischaemia cannot be excluded. Our hypothesis that volatile anaesthesia improved indices of cardiac function compared with total intravenous anaesthesia could not be verified.
Peri‐operative warming devices: performance and clinical application
Authors: John M. , Ford J. , Harper M. 
Published: April 2014

SummarySince the adverse consequences of accidental peri‐operative hypothermia have been recognised, there has been a rapid expansion in the development of new warming equipment designed to prevent it. This is a review of peri‐operative warming devices and a critique of the evidence assessing their performance. Forced‐air warming is a common and extensively tested warming modality that outperforms passive insulation and water mattresses, and is at least as effective as resistive heating. More recently developed devices include circulating water garments, which have shown promising results due to their ability to cover large surface areas, and negative pressure devices aimed at improving subcutaneous perfusion for warming. We also discuss the challenge of fluid warming, looking particularly at how devices’ performance varies according to flow rate. Our ultimate aim is to provide a guide through the bewildering array of devices on the market so that clinicians can make informed and accurate choices for their particular hospital environment.
A comparison of the predictive performance of three pharmacokinetic models for propofol using measured values obtained during target‐controlled infusion
Authors: Glen J. B. , White M. 
Published: April 2014

SummaryWe compared the predictive performance of the existing Diprifusor and Schnider models, used for target‐controlled infusion of propofol, with a new modification of the Diprifusor model (White) incorporating age and sex covariates. The bias and inaccuracy (precision) of each model were determined using computer simulation to replicate the infusion profiles in an earlier study of 41 patients undergoing surgery with propofol administered by target‐controlled infusion and in which timed, measured blood propofol concentrations were available. Bias with the White model (5%) was significantly less (p < 0.0001) than with the Diprifusor (16%) or Schnider (15%) models. The White model showed a significant improvement in accuracy (inaccuracy 19%, p < 0.0001) relative to the Diprifusor (26%). Temporal changes were such that with all three models, bias differed at induction and recovery. None of the models accounted fully for the extent of inter‐individual variation in propofol clearance, but the improved performance with the White model suggests it has merit.
Bridging the gap: a review of dose investigations in paediatric investigation plans
Authors: Hampson Lisa V. , Herold Ralf , Posch Martin , Saperia Julia , Whitehead Anne 
Published: April 2014

AimsIn the EU, development of new medicines for children should follow a prospectively agreed paediatric investigation plan (PIP). Finding the right dose for children is crucial but challenging due to the variability of pharmacokinetics across age groups and the limited sample sizes available. We examined strategies adopted in PIPs to support paediatric dosing recommendations to identify common assumptions underlying dose investigations and the attempts planned to verify them in children.MethodsWe extracted data from 73 PIP opinions recently adopted by the Paediatric Committee of the European Medicines Agency. These opinions represented 79 medicinal development programmes and comprised a total of 97 dose investigation studies. We identified the design of these dose investigation studies, recorded the analyses planned and determined the criteria used to define target doses.ResultsMost dose investigation studies are clinical trials (83 of 97) that evaluate a single dosing rule. Sample sizes used to investigate dose are highly variable across programmes, with smaller numbers used in younger children (< 2 years). Many studies (40 of 97) do not pre‐specify a target dose criterion. Of those that do, most (33 of 57 studies) guide decisions using pharmacokinetic data alone.ConclusionsCommon assumptions underlying dose investigation strategies include dose proportionality and similar exposure−response relationships in adults and children. Few development programmes pre‐specify steps to verify assumptions in children. There is scope for the use of Bayesian methods as a framework for synthesizing existing information to quantify prior uncertainty about assumptions. This process can inform the design of optimal drug development strategies.
Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data
Authors: Fiorentino Alessia , O'Brien Niamh Louise , Locke Devin Paul , McQuillin Andrew , Jarram Alexandra , Anjorin Adebayo , Kandaswamy Radhika , Curtis David , Blizard Robert Alan , Gurling Hugh Malcolm Douglas 
Published: April 2014

ObjectivesGenetic markers in the genes encoding ankyrin 3 (ANK3) and the α‐calcium channel subunit (CACNA1C) are associated with bipolar disorder (BP). The associated variants in the CACNA1C gene are mainly within intron 3 of the gene. ANK3 BP‐associated variants are in two distinct clusters at the ends of the gene, indicating disease allele heterogeneity.MethodsIn order to screen both coding and non‐coding regions to identify potential aetiological variants, we used whole‐genome sequencing in 99 BP cases. Variants with markedly different allele frequencies in the BP samples and the 1,000 genomes project European data were genotyped in 1,510 BP cases and 1,095 controls.ResultsWe found that the CACNA1C intron 3 variant, rs79398153, potentially affecting an ENCyclopedia of DNA Elements (ENCODE)‐defined region, showed an association with BP (p = 0.015). We also found the ANK3 BP‐associated variant rs139972937, responsible for an asparagine to serine change (p = 0.042). However, a previous study had not found support for an association between rs139972937 and BP. The variants at ANK3 and CACNA1C previously known to be associated with BP were not in linkage disequilibrium with either of the two variants that we identified and these are therefore independent of the previous haplotypes implicated by genome‐wide association.ConclusionsSequencing in additional BP samples is needed to find the molecular pathology that explains the previous association findings. If changes similar to those we have found can be shown to have an effect on the expression and function of ANK3 and CACNA1C, they might help to explain the so‐called ‘missing heritability’ of BP.
Insights into the Infiltrative Behavior of Adamantinomatous Craniopharyngioma in a New Xenotransplant Mouse Model
Authors: Stache Christina , Hölsken Annett , Schlaffer Sven‐Martin , Hess Andreas , Metzler Markus , Frey Benjamin , Fahlbusch Rudolf , Flitsch Jörg , Buchfelder Michael , Buslei Rolf 
Published: April 2014

AbstractAdamantinomatous craniopharyngiomas (adaCP) cause hypothalamic pituitary dysfunction. Elucidation of pathomechanisms underlying tumor progression is essential for the development of targeted chemotherapeutic treatment options. In order to study the mechanisms of tumor outgrowth, we implanted human primary adaCP tissue from three different surgical specimens stereotactically into the brain of immunodeficient mice (n = 20). Three months after tumor inoculation, magnetic resonance imaging and histology confirmed tumor engraftment in all 20 mice (100%) that obtained tissue transplants. The lesions invaded adjoining brain tissue with micro finger‐shaped protrusions. Immunohistochemical comparison of the primary tumor and xenotransplants revealed a similar amount of proliferation (Mib‐1) and cytokeratin expression pattern (KL‐1). Whole tumor reconstruction using serial sections confirmed whirl‐like cell clusters with nuclear β‐catenin accumulations at the tumor brain border. These whirls were surrounded by a belt of Claudin‐1 expressing cells, showed an activated epidermal growth factor receptor (EGFR) and distinct CD133 as well as p21WAF1/Cip1 positivity, indicating a tumor stem cell phenotype. Consistent with our previous in vitro studies, intracranial xenotransplants of adaCP confirmed cells with nuclear β‐catenin and activated EGFR being the driving force of tumor outgrowth. This model provides the possibility to study in vivo tumor cell migration and to test novel treatment regimens targeting this tumor stem cell niche.
Behavioural treatment recommendations in clinical practice guidelines for attention‐deficit/hyperactivity disorder: a scoping review
Authors: Vallerand Isabelle A. , Kalenchuk Anna L. , McLennan John D. 
Published: April 2014

BackgroundThe extent of behavioural treatment recommendations described in attention‐deficit/hyperactivity disorder (ADHD) practice guidelines has not been examined.MethodA scoping review identified eight agency‐based ADHD practice guidelines. Key components of behavioural treatment recommendations were summarized.ResultsAll guidelines mentioned behavioural treatment as a consideration for managing ADHD, however, the extent to which they were detailed varied. Most guidelines provided lists of behavioural techniques but with minimal specifics regarding treatment delivery.ConclusionsThere is far less detailing of behavioural approaches compared to pharmacological treatments for ADHD. Greater detailing of evidence‐based behavioural approaches may foster improved delivery of high‐quality behaviour treatment.
Familial isolated primary hyperparathyroidism/hyperparathyroidism‐jaw tumour syndrome caused by germline gross deletion or point mutations of CDC73 gene in Chinese
Authors: Kong Jing , Wang Ou , Nie Min , Shi Jie , Hu Yingying , Jiang Yan , Li Mei , Xia Weibo , Meng Xunwu , Xing Xiaoping 
Published: April 2014

SummaryObjectiveHyperparathyroidism‐jaw tumour syndrome (HPT‐JT) and familial isolated primary hyperparathyroidism (FIHP) are two subtypes of familial primary hyperparathyroidism, which are rarely reported in Chinese population. Here, we reported three FIHP families and one HPT‐JT family with long‐term follow‐up and genetic analysis.Design and methodsA total of 22 patients, from four FIHP/HPT‐JT families of Chinese descent, were recruited and genomic DNA was extracted from their peripheral blood lymphocytes. Direct sequencing for MEN1, CDC73, CASR gene was conducted. Reverse transcription PCR (RT–PCR) and quantitative real‐time PCR (qRT‐PCR) were used to study the effect of splice site mutations and gross deletion mutations. Immunohistochemistry was performed to analyse parafibromin expression in parathyroid tumours. Genotype–phenotype correlations were assessed through clinical characteristics and long‐term follow‐up data.ResultsGenetic analysis revealed four CDC73 germline mutations that were responsible for the four kindreds, including two novel point mutation (c.157 G>T and IVS3+1 G>A), one recurrent point mutation (c.664 C>T) and one deletion mutation (c.307+?_513‐?del exons 4, 5, 6). RT‐PCR confirmed that IVS3+1 G>A generated an aberrant transcript with exon3 deletion. Immunohistochemical analysis demonstrated reduced nuclear parafibromin expression in tumours supporting the pathogenic effects of these mutations.ConclusionsThis study supplies information on mutations and phenotypes of HPT‐JT/FIHP syndrome in Chinese. Screening for gross deletion and point mutations of the CDC73 gene is necessary in susceptible subjects.
Enclosures within Enclosures and Hurricane Reconstruction in Cancún, Mexico
Authors: AZCÁRATE MATILDE CÓRDOBA , BAPTISTA IDALINA , RUBIO FERNANDO DOMÍNGUEZ 
Published: April 2014

AbstractThis article focuses on the reconstruction processes undertaken in Cancún, Mexico after hurricanes Gilbert in 1988 and Wilma in 2005. The article argues that both hurricanes facilitated the creation of an evolving logic of “enclosures within enclosures,” whereby hotel and real estate investors, aided by government authorities, privatized and commoditized Cancún's public lands and resources for the exclusive use of the global tourism market. In practice, this meant a radical spatial, aesthetic, and economic reconfiguration of the Hotel Zone in Cancún from a low‐density luxury resort to a mass tourism, all‐inclusive resort destination after Gilbert, followed by the emergence of the contemporary timeshare high‐rise condominium model after Wilma. With each new business model, investors strategically used post‐hurricane reconstruction to redefine space, displace risk, and to reposition themselves and the city in global circuits of capital accumulation. The case of Cancún provides an empirically grounded example of how, in the aftermath of natural disasters, strategies of enclosure are deployed through approaches to governance, business models, and forms of architecture and surveillance all in the name of defending the public good, providing security, and enhancing economic growth.
Influence of placement depth on bone remodeling around tapered internal connection implants: a histologic study in dogs
Authors: Huang Baoxin , Meng Huanxin , Zhu Weidong , Witek Lukasz , Tovar Nick , Coelho Paulo G. 
Published: April 2014

AbstractObjectivesTo evaluate the influence of implant‐abutment interface (IAI) placement depth on bone remodeling around implants with two different types of tapered internal IAI: screwed‐in (SI) and tapped‐in (TI) connections in dogs.Materials and methodsEight weeks post mandibular tooth extraction in six beagle dogs, two SI implants (OsseoSpeed™, Astra Tech, DENTSPLY) and two TI implants (Integra‐CP™, Bicon LLC) were placed in one side of the mandible. The four experimental groups were as follows: (i) SI‐placed equicrestally (SIC); (ii) TI‐placed equicrestally (TIC); (iii) SI‐placed 1.5 mm subcrestally (SIS); and (iv) TI‐placed 1.5 mm subcrestally (TIS). Healing abutments were connected 12 weeks after implant placement. Sixteen weeks later, the dogs were sacrificed and histomorphometric analysis was performed. Histometrical outcomes were evaluated using a nonparametric Brunner–Langer model.ResultsMean distance from the IAI to first bone‐implant contact (IAI‐fBIC) was 0.88 mm (median: 0.77; SD: 0.54) for SIC group, 1.23 mm (median: 1.22; SD: 0.66) for TIC group, 0.41 mm (median: 0.31; SD: 0.36) for SIS group, and 0.41 mm (median: 0.26; SD: 0.45) for TIS group. Subcrestal groups showed lower IAI‐fBIC compared with equicrestal groups (P < 0.001). Connective tissue presented similar measurements regardless of the IAI placement depth and IAI type (P > 0.05), but the epithelium length and peri‐implant soft tissue length in subcrestal groups were significant larger than that in the equicrestal groups (P < 0.001 and P = 0.004, respectively).ConclusionSubcrestal implant placement with tapered internal IAI is beneficial for bone contact with the implant neck, and concurrently, it may not increase the soft tissue inflammation around IAI.
Assessment of periodontal and opportunistic flora in patients with peri‐implantitis
Authors: Albertini Matteo , López‐Cerero Lorena , O'Sullivan Manuel G. , Chereguini Carlos F. , Ballesta Sofia , Ríos Vicente , Herrero‐Climent Mariano , Bullón Pedro 
Published: April 2014

AbstractAimTo assess the presence of periodontal and opportunistic organisms in patients with peri‐implantitis.Material and methodsThirty‐three partially edentulous subjects (22 women, 11 men), aged 32–90 years, who had one or more implants with peri‐implantitis were included. Peri‐implantitis was defined as: (i) the presence of bleeding on probing and/or suppuration and (ii) radiographic images showed marginal bone loss >1.8 mm after 1 year in function. Criteria for inclusion were: (i) partially edentulous patients having at least one implant diagnosed with peri‐implantitis; (ii) no antibiotic therapy for 6 months prior to clinical examination. Following this definition, a total of 48 implants were diagnosed with peri‐implantitis. Subgingival bacterial samples were obtained with sterile paper points from infected implants and selected teeth of each individual. Periodontopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola) were detected by multiplex PCR targeting 16S rDNA. Samples were placed in reduced transport medium and cultured for opportunistic pathogens (Staphylococcus aureus, enteric bacteria, Pseudomonas and yeasts).ResultsTwenty‐two patients yielded positive results for P. gingivalis, 25 for T. forsythia, eight for P. intermedia and 13 for T. denticola. None of the patients yielded a positive result for A. actinomycetemcomitans. Non‐periodontal species were found in five patients (15% of total). P. aeruginosa was found in four (12%) patients, and C. albicans (3%) and S. aureus in one patient (3%) each. In two cases of peri‐implantitis, none of the periodontal or opportunistic microorganisms studied were detected in either implant or tooth samples. When results of the periodontopathic bacteria from the implant and tooth samples of the same patient were compared, 18 patients (54%) showed the same results for both samples and 15 (45%) patients different results.ConclusionsThe implant surface may be colonized with pathogens different from periodontal bacteria. Opportunistic pathogens such as P. aeruginosa, S. aureus and C. albicans may be associated with implant failure.