bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas
Authors: Nikolaev Sergey I. , Sotiriou Sotirios K. , Pateras Ioannis S. , Santoni Federico , Sougioultzis Stavros , Edgren Henrik , Almusa Henrikki , Robyr Daniel , Guipponi Michel , Saarela Janna , Gorgoulis Vassilis G. , Antonarakis Stylianos E. , Halazonetis Thanos D.
Published: November 2012

Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer. In particular, replication stress can explain the high prevalence of focal genomic deletions mapping within very large genes in human tumors. However, the origin of single-nucleotide substitutions (SNS) in nonfamilial cancers is strongly debated. Some argue that cancers have a mutator phenotype, whereas others argue that the normal DNA replication error rates are sufficient to explain the number of observed SNSs. Here, we sequenced the exomes of 24, mostly precancerous, colon polyps. Analysis of the sequences revealed mutations in the APC, CTNNB1, and BRAF genes as the presumptive cancer-initiating events and many passenger SNSs. We used the number of SNSs in the various lesions to calculate mutation rates for normal colon and adenomas and found that colon adenomas exhibit a mutator phenotype. Interestingly, the SNSs in the adenomas mapped more often than expected within very large genes, where focal deletions in response to DNA replication stress also map. We propose that single-stranded DNA generated in response to oncogene-induced replication stress compromises the repair of deaminated cytosines and other damaged bases, leading to the observed SNS mutator phenotype. Cancer Res; 72(23); 6279–89. ©2012 AACR.
A Systematic Literature Review of Complementary and Alternative Medicine Prevalence in EU
Authors: Eardley Susan , Bishop Felicity L. , Prescott Philip , Cardini Francesco , Brinkhaus Benno , Santos-Rey Koldo , Vas Jorge , von Ammon Klaus , Hegyi Gabriella , Dragan Simona , Uehleke Bernard , Fønnebø Vinjar , Lewith George
Published: November 2012

Background: Studies suggest that complementary and alternative medicine (CAM) is widely used in the European Union (EU). We systematically reviewed data, reporting research quality and the prevalence of CAM use by citizens in Europe; what it is used for, and why. Methods: We searched for general population surveys of CAM use by using Ovid MEDLINE (1948 to September 2010), Cochrane Library (1989 to September 2010), CINAHL (1989 to September 2010), EMBASE (1980 to September 2010), PsychINFO including PsychARTICLES (1989 to September 2010), Web of Science (1989 to September 2010), AMED (1985 to September 2010), and CISCOM (1989 to September 2010). Additional studies were identified through experts and grey literature. Cross-sectional, population-based or cohort studies reporting CAM use in any EU language were included. Data were extracted and reviewed by 2 authors using a pre-designed extraction protocol with quality assessment instrument. Results: 87 studies were included. Inter-rater reliability was good (kappa = 0.8). Study methodology and quality of reporting were poor. The prevalence of CAM use varied widely within and across EU countries (0.3–86%). Prevalence data demonstrated substantial heterogeneity unrelated to report quality; therefore, we were unable to pool data for meta-analysis; our report is narrative and based on descriptive statistics. Herbal medicine was most commonly reported. CAM users were mainly women. The most common reason for use was dissatisfaction with conventional care; CAM was widely used for musculoskeletal problems. Conclusion: CAM prevalence across the EU is problematic to estimate because studies are generally poor and heterogeneous. A consistent definition of CAM, a core set of CAMs with country-specific variations and a standardised reporting strategy to enhance the accuracy of data pooling would improve reporting quality.
What Attitudes and Needs Do Citizens in Europe Have in Relation to Complementary and Alternative Medicine?
Authors: Nissen Nina , Schunder-Tatzber Susanne , Weidenhammer Wolfgang , Johannessen Helle
Published: November 2012

Background: Surveys from several European countries suggest a European-wide increase in the use of Complementary and Alternative Medicine (CAM). To safeguard citizens’ rights concerning their healthcare, it is critical to gain an overview of citizens’ attitudes and to understand their expectations and needs regarding CAM. Methods: A review of literature was undertaken, based on systematic searches of the following electronic databases: PubMed, Web of Science, CINHAL, AMED, PsycINFO and PsycArticles; 189 articles met inclusion criteria. Articles were analysed thematically and their reporting quality assessed. Results: Despite the limited availability of research-based knowledge about citizens’ attitudes and needs concerning CAM in many European countries, some trends can be noted. Many citizens hold positive attitudes to CAM and wish for increasing access to CAM provision. Citizens call for impartial, reliable and trustworthy information to support informed decision-making, and some citizens wish for greater support and involvement of biomedical healthcare professionals in facilitating their healthcare choices. While citizens value distinct aspects of CAM practice, they are also critical consumers and support clear regulatory and educational frameworks to ensure the quality and safety of CAM provision and medicinal products. Conclusion: To gain knowledge on citizens’ needs and attitudes to CAM across Europe further research is required on 3 main issues: i) how citizens across Europe obtain information about CAM and the needs they may have for trustworthy information sources, ii) the local situations for accessing CAM and iii) citizens’ perspectives on the quality of care and safety of CAM provision and products.
Building a Sustainable Complementary and Alternative Medicine Research Network in Europe
Authors: Reiter Bettina , Baumhöfener Franziska , Dlaboha Meike , Odde Madsen Jesper , Regenfelder Stephanie , Weidenhammer Wolfgang
Published: November 2012

Background: Since CAMbrella is a networking project funded by the European Commission explicitly to build and sustain a complementary and alternative medicine (CAM) research network in Europe, communication and dissemination play a large role and form a work package of their own. The present article gives an outline of the communication and dissemination work in the CAMbrella consortium. The intensive building of sound internal communication is an essential part in establishing a functioning structure for collaboration in a diverse group of 16 partner institutions from 12 countries, as exists in the CAMbrella project. Methods: The means and tools for dissemination of results to the scientific community and the European public at large, as well as to the European policy makers, are presented. The development of the corporate design and a dissemination strategy are described in detail. In addition, some basic information regarding previous CAM research efforts, which might be interesting for future consortium building in the field of CAM research, is given. Results: Internal communication within a heterogeneous research group, the maintenance of a work-oriented style of communication and a consensus oriented effort in establishing dissemination tools and products will be essential for any future consortium in the CAM field. Conclusion: The outlook shows the necessity for active political encouragement of CAM research and the desideratum of a Pan-European institution analogous to the NIH (National Institutes of Health) in the USA.
International Development of Traditional Medicine / Complementary and Alternative Medicine Research – What Can Europe Learn?
Authors: Hök Johanna , Lewith George , Weidenhammer Wolfgang , Santos-Rey Koldo , Fønnebø Vinjar , Wiesener Solveig , Falkenberg Torkel
Published: November 2012

Background: The aim of this study was to analyse global research and development (R&D) strategies for traditional medicine (TM) and complementary and alternative medicine (CAM) across the world to learn from previous and on-going activities. Methods: 52 representatives within CAMbrella nominated 43 key international stakeholders (individuals and organisations) and 15 of these were prioritised. Information from policy documents including mission statements, R&D strategies and R&D activities were collected in combination with personal interviews. Data were analysed using the principles of content analysis. Results: Key stakeholders vary greatly in terms of capacity, mission and funding source (private/public). They ranged from only providing research funding to having a comprehensive R&D and communication agenda. A common shift in R&D strategy was noted; whereas 10 years ago research focused mainly on exploring efficacy and mechanisms, today the majority of stakeholders emphasise the importance of a broad spectrum of research, including methodologies exploring context, safety and comparative effectiveness. Conclusion: The scarce public investment in this field in Europe stands in stark contrast to the large investments found in Australia, Asia and North America. There is an emerging global trend supporting a broad research repertoire, including qualitative and comparative effectiveness research. This trend should be considered by the EU given the experience and the substantial research funding committed by the included stakeholders. To facilitate international collaborative efforts and minimise the risk of investment failure, we recommend the formation of a centralised EU CAM research centre fostering a broad CAM R&D agenda with the responsibility for implementing the relevant findings of CAMbrella.
Key Issues in Clinical and Epidemiological Research in Complementary and Alternative Medicine – a Systematic Literature Review
Authors: Fischer H. Felix , Junne Florian , Witt Claudia , von Ammon Klaus , Cardini Francesco , Fønnebø Vinjar , Johannessen Helle , Lewith George , Uehleke Bernhard , Weidenhammer Wolfgang , Brinkhaus Benno
Published: November 2012

Background: In the last 2 decades there has been a large increase in publications on complementary and alternative medicine (CAM). However, CAM research methodology was heterogeneous and often of low quality. The aim of this systematic review was to investigate scientific publications with regards to general issues, concepts and strategies. We also looked at research priorities and methods employed to evaluate the clinical and epidemiological research of CAM in the past to identify the basis for consensus-based research strategies. Methods: We performed a systematic literature search for papers published between 1990 and 2010 in 7 electronic databases (Medline, Web of Science, PsychArticles, PsycInfo, CINAHL, EMBASE and Cochrane Library) on December 16 and 17, 2010. In addition, experts were asked to nominate relevant papers. Inclusion criteria were publications dealing with research methodology, priorities or complexities in the scientific evaluation of CAM. All references were assessed in a multistage process to identify relevant papers. Results: From the 3,279 references derived from the search and 98 references contributed by CAM experts, 170 papers fulfilled the criteria and were included in the analysis. The following key issues were identified: difficulties in past CAM research (e.g., randomisation, blinding), utility of quantitative and qualitative research methods in CAM, priority setting in CAM research and specific issues regarding various CAM modalities. Conclusions: Most authors vote for the use of commonly accepted research methods to evaluate CAM. There was broad consensus that a mixed methods approach is the most suitable for gathering conclusive knowledge about CAM.
RANTES Polymorphisms and the Risk of Graft-versus-Host Disease in Human Leukocyte Antigen-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Shin Dong-Yeop , Kim Inho , Kim Jin Hee , Lee Yun-Gyoo , Kang Eun Joo , Cho Hyeon Jin , Lee Kyung-Hun , Kim Hye Jin , Park Eun-Hee , Lee Jong-Eun , Bae Ji-Yeon , See Cha Ja , Yoon Sung-Soo , Park Sung Sup , Han Kyou-Sup , Park Myoung Hee , Hong Yun-Chul , Park Seonyang , Kim Byoung Kook
Published: November 2012

We investigated the association between RANTES (regulated upon activation, normal T cell expressed and secreted) polymorphisms and clinical outcomes in patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Three RANTES gene polymorphisms, i.e. –403G/A (rs2107538), –28C/G (rs2280788) and In1.1T/C (rs2280789), were genotyped, and the effects of the genotypes and haplotypes of RANTES on clinical outcomes were analyzed. The competing risk regression analysis was used to investigate the relationship between the polymorphisms and the cumulative risk of graft-versus-host disease (GVHD). An AGC haplotype in a recessive model showed significant harmful effects on the cumulative risk of acute GVHD and relapse-free survival (adjusted hazard ratios 2.42 and 2.71, 95% confidence intervals 1.29–4.55 and 1.30–5.64; p = 0.018 and 0.024, respectively), whereas a GCT haplotype did not. RANTES polymorphisms were not significantly associated with overall survival and the risk of chronic GVHD. This study suggests that RANTES polymorphisms might be associated with the occurrence of acute GVHD rather than of chronic GVHD and also of relapse-free survival in the patients treated with allo-HSCT. Further larger prospective investigations are needed to establish the role of RANTES polymorphisms in patients treated with allo-HSCT.
Comprehensive Prediction Model of Urinary Incontinence One Year following Robot-Assisted Radical Prostatectomy
Authors: Barnoiu Ovidiu-Spiru , Baron Lopez Francisco , Garcia Galisteo Emilio , Soler Martinez Jorge , Vozmediano Chicharro Raul , Del Rosal Samaniego Jose Maria , Machuca Santacruz Javier , Navarro Vilchez Pablo , Sanchez Luque Javier , Bautista Vidal Carlos , Gomez Lechuga Pablo , Baena Gonzalez Victor
Published: November 2012

Objectives: Urinary incontinence (UI) still remains one of the major functional complications after robot-assisted radical prostatectomy (RARP). As the cause for UI is multifactorial, it is quite difficult to make a prediction preoperatively. Considering intraoperative and postoperative risk factors, besides the preoperative ones, we designed an incontinence prediction model, administered 1 month after the surgery, in order to identify incontinent patients at 1 year. Patients and Methods: We retrospectively reviewed 244 patients who underwent RARP at our institution. Only 209 patients had sufficient data, a 1-year follow-up and were continent preoperatively. The association of UI with the risk factors was assessed by univariable and multivariable regression models. Results: There was a 17.2% global UI rate at 1 year after RARP. Only age-adjusted Charlson comorbidity index, erectile function assessed by International Index of Erectile Function-5, prostate volume, nerve-sparing status and 24-hour urine loss at 1 month correlated with UI (p = 0.032, 0.009, 0.031, 0.018 and <0.001, respectively). The accuracy of the prediction model of UI was 92.8% (c-index), with an area under the curve of 91.9%. Conclusion: Age-adjusted Charlson comorbidity index, International Index of Erectile Function-5, prostate volume, nerve-sparing status and 24-hour urine loss at 1 month after RARP can predict an individual’s risk of UI at 1 year after RARP with good accuracy. Further external validation is required in order to generalize the use of this model.
Towards a Pan-European Definition of Complementary and Alternative Medicine – a Realistic Ambition?
Authors: Falkenberg Torkel , Lewith George , Roberti di Sarsina Paolo , von Ammon Klaus , Santos-Rey Koldo , Hök Johanna , Frei-Erb Martin , Vas Jorge , Saller Reinhard , Uehleke Bernhard
Published: November 2012

Background: The terms used for defining complementary and alternative medicine (CAM) including the methods, procedures and therapies vary greatly. The task of the CAMbrella working group on terminology was to explore the existing CAM terminologies and to develop a pragmatic definition of CAM that is acceptable Europewide. This can then be used to systematically research, e.g., its prevalence and legal status and to investigate the citizens’ demands on CAM and the perspectives of providers of CAM in Europe. Methods: Terms and definitions were collected from both scientific and non-scientific sources. The terms and definitions identified were analysed and discussed among the CAMbrella working group participants on several occasions with the aim of arriving at a consensus. Results: We developed a proposal for a pragmatic European definition of CAM: ‘Complementary and alternative medicine (CAM) utilised by European citizens represents a variety of different medical systems and therapies based on the knowledge, skills and practices derived from theories, philosophies and experiences used to maintain and improve health, as well as to prevent, diagnose, relieve or treat physical and mental illnesses. CAM has been mainly used outside conventional health care, but in some countries certain treatments are being adopted or adapted by conventional health care.’ Conclusion: Developing a uniform, pragmatic pan-European definition of CAM was complicated by a number of factors. These included the vast diversity of existing definitions, systems, disciplines, procedures, methods and therapies available within the EU.
Goethe's Anxieties, Depressive Episodes and (Self-)Therapeutic Strategies: A Contribution to Method Integration in Psychotherapy
Authors: Holm-Hadulla Rainer M.
Published: November 2012

Background: In psychiatry and psychotherapy, abstract scientific principles need to be exemplified by narrative case reports to gain practical precision. Goethe was one of the most creative writers, productive scientists, and effective statesmen that ever lived. His descriptions of feelings, emotions, and mental states related to anxieties, depressive episodes, dysthymia, and creativity are unique in their phenomenological precision and richness. His life and work can thus serve as an excellent example enhancing our understanding of the relationship between anxiety, depression and creativity. Furthermore, he described (self-)therapeutic strategies that reinforce and refine modern views. Methods: Goethe's self-assessments in his works and letters, and the descriptions by others are analyzed under the perspective of current psychiatric classification. His therapeutic techniques and recommendations are compared with cognitive-behavioral, psychodynamic, and existential psychotherapy to amplify modern concepts of psychotherapy. Results: From a scientific perspective, several distinctive depressive episodes can be diagnosed in Goethe's life. They were characterized by extended depressive moods, lack of drive, and loss of interest and self-esteem combined with social retreat. Goethe displayed diffuse and phobic anxieties as well as dysthymia. His (self-)therapeutic strategies were: (a) the systematic use of helping alliances, (b) behavioral techniques, (c) cognitive reflection on meanings and beliefs, (d) psychodynamic and psychoanalytic remembering, repeating, and working through, and (e) existential striving for self-actualization, social commitment, meaning, and creativity. Conclusions: In Goethe's life, creative incubation, illumination, and elaboration appear to have been associated with psychic instability and dysthymia, sometimes with depressive episodes in a clinical sense. On the one hand, his creative work was triggered by anxieties, dysthymia, and depressive moods. On the other hand, his creativity helped him to cope with psychic disorders and suicidal tendencies. Furthermore, Goethe described psychotherapeutic strategies that resemble modern techniques. He integrated relational, behavioral, cognitive, psychodynamic, and existential techniques and attitudes. These modern psychotherapeutic approaches can be exemplified and enhanced by reflecting upon the (self-)therapeutic efforts of one of the most creative persons that have ever lived. Hermeneutics as the art of communication and understanding derived from Goethe's (self-)therapy and creative works can serve as a meta-theoretical framework for the integration of different psychotherapeutic approaches.
Thrombin-activatable fibrinolysis inhibitor in hypothyroidism and hyperthyroxinaemia
Authors: Verkleij Chantal , van Zaane Bregje , Squizzato Alessandro , Brandjes Dees , Büller Harry , Meijers Joost , Gerdes Victor , Stuijver Danka
Published: November 2012

Endocrine disorders affect both the coagulation and fibrinolytic systems, and have been associated with the development of cardiovascular diseases. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a link between coagulation and the fibrinolytic system. The aim of this study was to determine the effect of thyroid hormone excess and deficiency on TAFI levels and function. The effect of hyperthyroxinemia on TAFI was studied in healthy volunteers who were randomised to receive levothyroxine or no medication for 14 days in a crossover design. The effect of hypothyroidism on TAFI was studied in a multicentre observational cohort study. Blood was drawn before treatment of patients with newly diagnosed hypothyroidism and when euthyroidism was achieved. Plasma clot-lysis times, activated TAFI (TAFIa)-dependent prolongation of clot-lysis and TAFI levels were measured. Thyroid hormone excess resulted in a hypofibrinolytic condition and in an enhanced TAFIa-dependent prolongation of clot lysis. A trend towards decreased plasma TAFI levels was observed in healthy volunteers who used levothyroxine. Hypothyroidism resulted in hyperfibrinolysis and a reduced TAFIa-dependent prolongation of clot lysis. In conclusion, alterations of TAFIa-dependent prolongation of clot lysis in patients with thyroid disorders may cause an impaired haemostatic balance. The disturbed haemostatic balance in patients with hyperthyroidism might make them prone to thrombosis, while the risk for bleeding may increase in patients with hypothyroidism.
Creating a genotype-based dosing algorithm for acenocoumarol steady dose
Authors: Cerezo-Manchado Juan J. , Rosafalco Mario , Antón Ana , Perez-Andreu Virginia , Garcia-Barberá Nuria , Martínez Ana B. , Corral Javier , Vicente Vincente , González-Conejero Rocio , Roldán Vanessa
Published: November 2012

Acenocoumarol is a commonly prescribed anticoagulant drug for the prophylaxis and treatment of venous and arterial thromboembolic disorders in several countries. In counterpart of warfarin, there is scarce information about pharmacogenetic algorithms for steady acenocoumarol dose estimation. The aim of this study was to develop an algorithm of prediction for acenocoumarol.The algorithm was created using the data from 973 retrospectively selected anticoagulated patients and was validated in a second independent cohort adding up to 2,683 patients. The best regression model to predict stable dosage in the Primary Cohort included clinical factors (age and body mass index, BSA) and genetic variants (VKORC1, CYP2C9* and CYP4F2 polymorphisms) and explained up to 50% of stable dose. In the validation study the clinical algorithm yielded an adjusted R2=0.15 (estimation´s standard error=4.5) and the genetic approach improved the dose forecast up to 30% (estimation´s standard error=4.6). Again, the best model combined clinical and genetic factors (R2= 0.48; estimation´s standard error=4) which provided the best results of doses estimates within 20% of the real dose in patients taking lower (≤7mg/week) or higher (≥25mg/week) acenocoumarol doses. In conclusion, we developed a prediction algorithm using clinical data and three polymorphisms in VKORC1, CYP2C9* and CYP4F2 genes that provided a steady acenocoumarol dose for about 50% of patients in the Validation Cohort. Such algorithm was especially useful to patients who need higher or lower acenocoumarol doses, those patients with higher time required until their stabilisation and are more prone to suffer a treatment derived complication.
Increased Dietary Intake of Vitamin A Promotes Aortic Valve Calcification In Vivo
Authors: Huk Danielle J. , Hammond Harriet L. , Kegechika Hiroyuki , Lincoln Joy
Published: November 2012

Objective—

Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor
Sox9
. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro.

Methods and Results—

Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated
Sox9
repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors.

Conclusion—

Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.
Phosphorylation of Protein Inhibitor of Activated STAT1 (PIAS1) by MAPK-Activated Protein Kinase-2 Inhibits Endothelial Inflammation via Increasing Both PIAS1 Transrepression and SUMO E3 Ligase Activity
Authors: Heo Kyung-Sun , Chang Eugene , Takei Yuichiro , Le Nhat-Tu , Woo Chang-Hoon , Sullivan Mark A. , Morrell Craig , Fujiwara Keigi , Abe Jun-ichi
Published: November 2012

Objective—

Protein inhibitor of activated signal transducer and activator of transcription-1 (PIAS1) is known to function as small ubiquitin-like modifier (SUMO) E3 ligase as well as transrepressor. The aim of the study is to elucidate the regulatory mechanisms for these 2 different functions, especially with respect to endothelial inflammation.

Methods and Results—

The mitogen-activated protein kinase (MAPK)-activated protein kinase-2 is a proinflammatory kinase and phosphorylates PIAS1 at the Ser522 residue. Activation of MAPK-activated protein kinase-2 enhances p53-SUMOylation, but a PIAS1 phosphorylation mutant, PIAS1-S522A, abolished this p53-SUMOylation, suggesting a critical role for PIAS1-S522 phosphorylation in its SUMO ligase activity. Because nuclear p53 can inhibit Kruppel-like factor 2 promoter activity, we investigated the roles for PIAS1 phosphorylation and p53-SUMOylation in the Kruppel-like factor 2 and endothelial NO synthase expression. Both MAPK-activated protein kinase-2 and PIAS1 overexpression increased Kruppel-like factor 2 promoter activity and endothelial NO synthase expression, which were inhibited by expressing a p53-SUMOylation defective mutant, p53-K386R, and PIAS1-S522A. PIAS1-S522A also abolished the anti-inflammatory effect of wild-type PIAS1 in vitro and also in vivo, which was examined by leukocyte rolling in microvessels of skin grafts transduced by adenovirus encoding PIAS1-WT or - S522A mutant.

Conclusion—

Our study has identified a novel negative feedback regulatory pathway through which MAPK-activated protein kinase-2 limits endothelial inflammation via the PIAS1 S522 phosphorylation-mediated increase in PIAS1 transrepression and SUMO ligase activity.
Reference Values for and Determinants of Right Atrial Area in Healthy Adults by 2-Dimensional Echocardiography
Authors: Grünig Ekkehard , Henn Philipp , D’Andrea Antonello , Claussen Martin , Ehlken Nicola , Maier Felicitas , Naeije Robert , Nagel Christian , Prange Felix , Weidenhammer Johannes , Fischer Christine , Bossone Eduardo
Published: November 2012

Background—

Right atrial (RA) size is important in screening, diagnosis, and follow-up assessment in patients with pulmonary hypertension. The objective of this study was to define normal reference values for RA area by echocardiography in a large population of athletic versus sedentary healthy subjects.

Methods and Results—

In the first part of the study, 880 healthy adult subjects (mean age, 28±6 years; 38% women; 395 top-level endurance athletes, 255 strength athletes, and 230 nonathletes) were prospectively assessed. In the second part, we performed a pooled analysis of all studies published between 1976 and 2011 describing RA area in healthy subjects (n=624). Statistical analysis included the calculation of 95% quantiles for defining cutoff values. Mean RA area in the 880 subjects was significantly larger in endurance athletes compared with the strength athletes and nonathletes. RA area correlated significantly with age, sex, body surface, and endurance training. In a synopsis of both data sets, 95% quantiles for RA area in strength atheletes and nonathletes were 15.2 cm
2
(95% confidence interval, 14.7–15.7) in women and 16.2 cm
2
(95% confidence interval, 15.8–16.6) in men.

Conclusions—

To the best of our knowledge, this is the largest data set to describe RA size in adult healthy subjects (age <50 years). Cutoff values for RA area were significantly different in women (15 cm
2
) and men (16 cm
2
). Age, sex, body surface area, and high-level endurance training were determinants of RA area.
Familial Intracranial Aneurysms
Authors: Mackey Jason , Brown Robert D. , Moomaw Charles J. , Hornung Richard , Sauerbeck Laura , Woo Daniel , Foroud Tatiana , Gandhi Dheeraj , Kleindorfer Dawn , Flaherty Matthew L. , Meissner Irene , Anderson Craig , Rouleau Guy , Connolly E. Sander , Deka Ranjan , Koller Daniel L. , Abruzzo Todd , Huston John , Broderick Joseph P. ,   For the FIA Investigators
Published: November 2012

Background and Purpose—

Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study.

Methods—

We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family’s proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and
P
values from the 1001 logistic regression analyses were used to represent the final results of the analysis.

Results—

There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04–2.27];
P
=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22–3.22];
P
=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05–8.24],
P
=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34–2.46];
P
<0.001).

Conclusions—

In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.
MR-DWI–Positive Lesions and Symptomatic Ischemic Complications After Coiling of Unruptured Intracranial Aneurysms
Authors: Kang Dong-Hun , Kim Byung Moon , Kim Dong Joon , Suh Sang Hyun , Kim Dong Ik , Kim Yong-Sun , Huh Seung Kon , Park Jaechan , Lee Jae Whan , Kim Yong Bae
Published: November 2012

Background and Purpose—

The aims of this study are to evaluate the risk factors for symptomatic ischemic complication (symptomatic ischemic complication [SIC], transient ischemic attack, or stroke) and microembolisms detected as MR diffusion-weighted imaging (MR-DWI)–positive (DWI(+)) lesions, and the relationship between DWI(+) and SIC after coiling of unruptured intracranial aneurysm.

Methods—

Between March 2009 and November 2011, 382 unruptured intracranial aneurysms in 343 patients underwent both coiling and posttreatment MR-DWI. The incidence of and risk factors for SIC and DWI(+), and the relationship between DWI(+) and SIC were retrospectively analyzed.

Results—

The incidence of SIC was 4.1%. The incidence of DWI(+) was 54.5%. The number of DWI(+) lesions was significantly larger in the SIC group, than in the asymptomatic one (12.1±10.4 versus 5.0±8.7,
P
<0.00). The cutoff value of DWI(+) for predicting SIC was ≥6 (sensitivity 85.7%, specificity 70.7%). The patients with DWI(+) ≥6 was 28.6%. Of the patients with SIC, the patients with DWI(+) ≥6 was 78.6%. Patients aged≥65 years had a trend for SIC, and it was the only independent risk factor for DWI(+) ≥cutoff (n=6; 95%CI, 1.167–3.083).

Conclusions—

The number of DWI(+) lesions was significantly larger in the SIC group than in the asymptomatic one after coiling of unruptured intracranial aneurysm. Patients aged≥65 had a trend for SIC, and it was the only independent risk factor for the number of DWI(+) ≥cutoff value (n=6) for predicting SIC.
Symptomatic Recurrence of Intracranial Arterial Dissections
Authors: Ono Hideaki , Nakatomi Hirofumi , Tsutsumi Kazuo , Inoue Tomohiro , Teraoka Akira , Yoshimoto Yuhei , Ide Takafumi , Kitanaka Chifumi , Ueki Keisuke , Imai Hideaki , Saito Nobuhito
Published: November 2012

Background and Purpose—

The frequency and pattern of symptomatic recurrence of spontaneous intracranial arterial dissection (IAD) are unknown.

Methods—

A follow-up study of 143 patients (85 men, 58 women; mean age, 50.7 [7–83] years) with spontaneous IADs at The University of Tokyo and affiliated hospitals from 1980 to 2000 was conducted. Tissue samples of IAD vessels obtained from 13 patients at various intervals from onset were also examined histologically.

Results—

With a mean follow-up of 8.2 years, symptomatic recurrence occurred in 47 patients (33%). Of 37 cases initially presenting with hemorrhage, 35 developed hemorrhagic recurrence with a mean interval of 4.8 days, and 2 developed nonhemorrhagic recurrences after 21 and 85 months, respectively. Of 10 patients initially presenting with nonhemorrhagic symptoms, 1 developed hemorrhagic recurrence 4 days later, and 9 developed nonhemorrhagic recurrences with a mean interval of 8.6 months. Histopathologically, the affected vessels in the acute stage of hemorrhage (days 0–6) demonstrated insufficient granulation formation within the pseudolumen, followed by marked intimal thickening around the pseudolumen and recanalizing vessel formation in the late stage (>day 30). In the late stage of brain ischemia, subintimal and subadventitial hemorrhage accompanied with intimal thickening was observed.

Conclusions—

These data indicate that IAD is a disease carrying a relatively high risk of symptomatic recurrence, apparently occurring in 3 phases and patterns: early hemorrhagic recurrence, late nonhemorrhagic recurrence, and chronic fusiform aneurysm transformation. Knowledge of this triphasic recurrence and corresponding histopathological characteristics help determine the treatment and follow-up strategy for IAD patients.
The Neurorestorative Benefit of GW3965 Treatment of Stroke in Mice
Authors: Cui Xu , Chopp Michael , Zacharek Alex , Cui Yisheng , Roberts Cynthia , Chen Jieli
Published: November 2012

Background and Purpose—

GW3965, a synthetic liver X receptor agonist, elevates high-density lipoprotein cholesterol and has antiatherosclerosis and anti-inflammation properties. We tested the hypothesis that GW3965 treatment of stroke increases vascular remodeling, promotes synaptic protein expression and axonal growth in the ischemic brain, and improves functional outcome in mice.

Methods—

Mice were subjected to transient middle cerebral artery occlusion and treated without or with different doses of GW3965 (5, 10, or 20 mg/kg) starting 24 hours after middle cerebral artery occlusion daily for 14 days. Neurological functional tests, blood high-density lipoprotein cholesterol measurement, and immunostaining were performed. Mouse brain endothelial cells, primary cultured artery explants, and primary cortical neurons cultures were also used in vitro.

Results—

GW3965 treatment of stroke significantly increased blood high-density lipoprotein cholesterol level, synaptic protein expression, axonal density, angiogenesis and arteriogenesis, and Angiopoietin1, Tie2, and occludin expression in the ischemic brain and improved functional outcome compared with middle cerebral artery occlusion control animals (n=10;
P
<0.05). In vitro, GW3965 and high-density lipoprotein cholesterol also significantly increased capillary-like tube formation and artery explant cell migration as well as neurite outgrowth. Inhibition of Angiopoietin-1 attenuated GW3965-induced tube-formation, artery cell migration, and neurite outgrowth (n=6 per group;
P
<0.05).

Conclusions—

These data indicate, for the first time, that GW3965 promotes synaptic protein expression and axonal growth and increases vascular remodeling, which may contribute to improvement of functional outcome after stroke. Increasing Angiopoietin-1/Tie2 signaling activity may play an important role in GW3965-induced brain plasticity and neurological recovery from stroke.
Estimating Central Equatorial Pacific SST Variability over the Past Millennium. Part I: Methodology and Validation
Authors: Emile-Geay Julien , Cobb Kimberly M. , Mann Michael E. , Wittenberg Andrew T.
Published: November 2012

Constraining the low-frequency (LF) behavior of general circulation models (GCMs) requires reliable observational estimates of LF variability. This two-part paper presents multiproxy reconstructions of Niño-3.4 sea surface temperature over the last millennium, applying two techniques [composite plus scale (CPS) and hybrid regularized expectation maximization (RegEM) truncated total least squares (TTLS)] to a network of tropical, high-resolution proxy records. This first part presents the data and methodology before evaluating their predictive skill using frozen network analysis (FNA) and pseudoproxy experiments. The FNA results suggest that about half of the Niño-3.4 variance can be reconstructed back to A.D. 1000, but they show little LF skill during certain intervals. More variance can be reconstructed in the interannual band where climate signals are strongest, but this band is affected by dating uncertainties (which are not formally addressed here). The CPS reliably estimates interannual variability, while LF fluctuations are more faithfully reconstructed with RegEM, albeit with inevitable variance loss. The RegEM approach is also tested on representative pseudoproxy networks derived from two millennium-long integrations of a coupled GCM. The pseudoproxy study confirms that reconstruction skill is significant in both the interannual and LF bands, provided that sufficient variance is exhibited in the target Niño-3.4 index. It also suggests that FNA severely underestimates LF skill, even when LF variability is strong, resulting in overly pessimistic performance assessments. The centennial-scale variance of the historical Niño-3.4 index falls somewhere between the two model simulations, suggesting that the network and methodology presented here would be able to capture the leading LF variations in Niño-3.4 for much of the past millennium, with the caveats noted above.
Kinematic and Thermodynamic Structures of Sierra Barrier Jets and Overrunning Atmospheric Rivers during a Landfalling Winter Storm in Northern California
Authors: Kingsmill David E. , Neiman Paul J. , Moore Benjamin J. , Abel Mimi R. , Yuter Sandra E. , Ralph F. Martin
Published: November 2012

This study characterizes kinematic and thermodynamic structures of Sierra barrier jets (SBJs), atmospheric rivers (ARs), and their interaction over the period 14–16 February 2011 when a winter storm made landfall in northern California. A suite of scanning and profiling Doppler radars, rawinsondes, and GPS receivers is used to document these structures across the Central Valley and up the western Sierra slope to the crest along an ~200-km segment of the Sierra. The winter storm is grouped into two episodes, each having an AR that made landfall. Low-level winds in the SBJ observed during episode 1 were southeasterly and embedded in a stably stratified air mass. Along-barrier wind speeds U340 reached maximum values of 25–30 m s−1, as low as ~0.2 km MSL over the Central Valley, and as high as ~1.5 km MSL over the western Sierra slope. Southwesterly winds associated with the AR overlaid the SBJ along an interface that sloped upward from southwest to northeast with a southwestern extent at the western edge of the Central Valley. In contrast, low-level winds in the SBJ observed during episode 2 were more southerly and embedded in a less stable air mass. The U340 reached maximum values that were slightly weaker (~20–25 m s−1) and spread over a thicker layer that extended to higher levels over the western Sierra (~2.5 km MSL). Southwesterly winds associated with the AR overlaying the SBJ tilted upward from southwest to northeast with a steeper slope but did not extend as far southwest.
Risk Score for the Prediction of Contrast-Induced Nephropathy in Elderly Patients Undergoing Percutaneous Coronary Intervention
Authors: Fu Naikuan , Li Ximing , Yang Shicheng , Chen Yongli , Li Qiong , Jin Dongxia , Cong Hongliang
Published: November 2012

We developed a risk score for contrast-induced nephropathy (CIN) in elderly patients (n = 668) before percutaneous coronary intervention (PCI). Another 277 elderly patients were studied for validation. Based on the odds ratio, risk factors were assigned a weighted integer; the sum of the integers was the risk score. Among the 668 elderly patients, 105 (15.7%) experienced CIN. There were 9 risk factors for CIN (with weighted integer): estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (4), diabetes (3), left ventricular ejection fraction <45% (3), hypotension (2), age >70 years (2), myocardial infarction (2), emergency PCI (2), anemia (2), and contrast agent volume >200 mL (2). The incidence of CIN was 3.4%, 11.9%, 36.9%, and 69.8% in the low-risk (≤4), moderate risk (5-8), high-risk (9-12), and very-high-risk groups (≥13). The model demonstrated good discriminative power in the validation population ( c statistic = 0.79). This score can be used to plan preventative measures.
Screening for Sleep Disorders in Pediatric Primary Care
Authors: Erichsen Daniel , Godoy Cecilia , Gränse Fanny , Axelsson John , Rubin David , Gozal David
Published: November 2012

Objectives. Obstructive sleep apnea (OSA) and habitual snoring are highly prevalent childhood conditions and have been associated with a large array of negative health outcomes. Although guidelines were published by the American Academy of Pediatrics (AAP) a decade ago recommending routine screening of sleep-disordered breathing (SDB) in primary care settings, it remains unclear to what extent such guidelines have been implemented and resulted in effective SDB screening. The aim of this study was to determine if AAP guidelines are adhered to in pediatric primary care. Study design. In all, 1032 electronic charts of children 4 to 17 years old presenting for well-child visits to 17 pediatricians between January 1 and December 31, 2010, were manually reviewed. Abstracted data included demographic variables and documentation of snoring as well as other sleep-related complaints. Results. The mean age was 8.5 ± 3.9 years (mean ± standard deviation), 49.9% were male, and 79.7% were Hispanic; 24.4% (n = 252) were screened for snoring. Of the children screened for sleep-related issues, 34.1% (n = 86) snored, but the majority of them (61.6%, n = 53) received no further evaluation. In the present sample, 0.5% (n = 5) had a diagnosis of OSA. Conclusions. The low prevalence of OSA may be explained by the relatively low frequency of sleep-related problem screening by pediatricians and thus the inordinately low adherence to the AAP guidelines. Modification and transition to electronic medical records as well as expanded efforts to educate health care providers and caregivers may improve detection and timely treatment of children at risk for SDB.
Seeing Beyond Your Visual Field
Authors: Barton Kevin R. , Valtchanov Deltcho , Ellard Colin
Published: November 2012

Previous research has suggested that the layout of urban spaces can have a substantial influence on how people navigate through those spaces. However, to date, few studies have directly investigated how changes in layout interact with changes in visual field to shape a person’s route choice. Across two experiments, the influence of visual field and spatial layout was manipulated using virtual reality. It was found that route choice was significantly influenced by the configuration of a space—The more consistently organized environment led to more systematic route choices. However, limiting the perception of distant visual information was found to influence route choice in a similar but completely independent way. These findings suggest that navigation in urban spaces is dependent on the interaction between topology and the visual features of the space, where greater visual field and a consistently organized spatial layout lead to maximally efficient route choices.
Discretion in employment relations policy among foreign-controlled multinationals in Canada
Authors: Bélanger Jacques , Lévesque Christian , Jalette Patrice , Murray Gregor
Published: November 2012

This article assesses the extent to which the foreign-controlled subsidiaries of multinational firms have the discretion to establish their employment relations policies. Drawing on a survey of the activities of foreign-controlled multinational companies in Canada, it considers three lines of analysis: the parent company’s country of origin, the subsidiary’s specific organizational capabilities and its position in global value chains. While our results confirm that US-controlled subsidiaries have lower discretion than those from continental Europe and Asia, they also highlight the need to go beyond country-of-origin analysis. Organizational capabilities and the subsidiary’s role in global value chains are also important predictors of subsidiary discretion on employment relations policy.
Housing Shadow Prices in an Inundation-prone Suburb
Authors: Rambaldi Alicia N. , Fletcher Cameron S. , Collins Kerry , McAllister Ryan R.J.
Published: November 2012

For flood-prone urban areas, the prospect of increasing population densities and more frequent extreme weather associated with climate change is alarming. Proactive adaptation can reduce potential flood risks in theory. However, there is limited empirical economics exploring this issue, without which convincing residents within exposed areas to participate in adaptation is challenging. In this paper, a hedonic model is presented of property prices for a flood-prone inner-city suburb of Brisbane, Australia. The study defines a continuous flood-risk variable based on the vertical distances of properties relative to a flood level that occurs on average once every 100 years. The results show significant property-price discounting of 5.5 per cent per metre below the defined flood level. Detailed hedonic characteristics also provided shadow price estimates of housing characteristics and distances to amenities (such as bus-stops, train-stations, parks and bikeways) and these hedonics need to be considered when holistically assessing the dynamics of suburbs for adaptation planning.