bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Optimal Sensor Placement Strategy Based on Modified Modal Assurance Criterion and Improved Adaptive Genetic Algorithm for Structural Health Monitoring
Authors: He Can , Xing Jianchun , Li Juelong , Yang Qiliang , Wang Ronghao , Zhang Xun
Published: March 2015

Optimal sensor placement (OSP) is an important part in the structural health monitoring. Due to the ability of ensuring the linear independence of the tested modal vectors, the minimum modal assurance criterion (minMAC) is considered as an effective method and is used widely. However, some defects are present in this method, such as the low modal energy and the long computation time. A new OSP method named IAGA-MMAC is presented in this study to settle the issue. First, a modified modal assurance criterion (MMAC) is proposed to improve the modal energy of the selected locations. Then, an improved adaptive genetic algorithm (IAGA), which uses the root mean square of off-diagonal elements in the MMAC matrix as the fitness function, is proposed to enhance computation efficiency. A case study of sensor placement on a numerically simulated wharf structure is provided to verify the effectiveness of the IAGA-MMAC strategy, and two different methods are used as contrast experiments. A comparison of these strategies shows that the optimal results obtained by the IAGA-MMAC method have a high modal strain energy, a quick computational speed, and small off-diagonal elements in the MMAC matrix.
PiecewiseH∞Static Output Feedback Controller Design for Nonlinear Systems Based on T-S Affine Fuzzy Models
Authors: Zhao Xingang
Published: March 2015

This paper is concerned with the problem of designingH∞controllers via static output feedback controller for a class of complex nonlinear systems, which is approximated by continuous-time affine fuzzy models. A decomposition method is presented to divide the output-space into different operating regions and interpolation regions. Based on this partition, a novel piecewise controller with affine terms via static output feedback is designed. By using a dilated linear matrix inequality (LMI) characterization, some nonconvex conditions are converted into convex ones to make the asymptotic stability andH∞performance of the closed-looped system. The effectiveness of the proposed method is illustrated by a numerical example.
Measurement of Cytokines and Adhesion Molecules in the First 72 Hours after Severe Trauma: Association with Severity and Outcome
Authors: Sousa António , Raposo Frederico , Fonseca Sara , Valente Luís , Duarte Filipe , Gonçalves Moura , Tuna Diana , Paiva José-Artur
Published: March 2015

Introduction. Severity and outcome assessments are crucial in trauma. Our aim was to describe the role of a group of cytokines (TNFα, IL-6, IL-10, and HMGB-1) and ICAM-1 as severity and outcome assessment tools and their kinetics in the first 72 h after severe trauma.Materials and Methods. Authors designed a prospective cohort study of severe polytrauma patients (ISS > 15) in a level 1 Trauma Centre. Cytokines and ICAM-1 levels and Th1/Th2 ratios were assessed at admission, 24, 48, and 72 h. SIRS, SIRS with hypoperfusion, and shock were identified. Outcomes considered were ICU admission, ARDS, MODS, and death.Results. Ninety-nine patients were enrolled (median ISS: 29 and age 31). There was an early release of pro- and anti-inflammatory mediators with higher values at admission (except for ICAM-1). On admission, IL-6 was associated with ISS, IL-10 with SIRS with hypoperfusion, and HMGB-1 with shock. Several cytokines were associated with outcomes, especially IL-6 and IL-10 at 72 h with MODS and death. Low TNFα/IL-10 and IL-6/IL-10 ratios at 24 and 72 h were associated with MODS and death.Conclusions. Pro- and anti-inflammatory responses occur simultaneously and earlier after injury. Cytokines may be useful for outcome assessment, especially IL-6 and IL-10. Low Th1/Th2 ratio at 24 to 72 h is associated with MODS and death.
Antiproliferative and Apoptosis Induction Potential of the Methanolic Leaf Extract ofHolarrhena floribunda(G. Don)
Authors: Badmus J. A. , Ekpo O. E. , Hussein A. A. , Meyer M. , Hiss D. C.
Published: March 2015

Natural plant products with potent growth inhibition and apoptosis induction properties are extensively being investigated for their cancer chemopreventive potential.Holarrhena floribunda(HF) is used in a wide range of traditional medicine practices. The present study investigated the antiproliferative and apoptosis induction potential of methanolic leaf extracts of HF against breast (MCF-7), colorectal (HT-29), and cervical (HeLa) cancer cells relative to normal KMST-6 fibroblasts. The MTT assay in conjunction with the trypan blue dye exclusion and clonogenic assays were used to determine the effects of the extracts on the cells. Caspase activities were assayed with Caspase-Glo 3/7 and Caspase-9 kits. Apoptosis induction was monitored by flow cytometry using the APOPercentage and Annexin V-FITC kits. Reactive oxygen species (ROS) was measured using the fluorogenic molecular probe 5-(and-6)-chloromethyl-2′,7′-dichlorofluorescein diacetate acetyl ester and cell cycle arrest was detected with propidium iodide. Dose-response analyses of the extract showed greater sensitivity in cancer cell lines than in fibroblast controls. Induction of apoptosis, ROS, and cell cycle arrest were time- and dose-dependent for the cancer cell lines studied. These findings provide a basis for further studies on the isolation, characterization, and mechanistic evaluation of the bioactive compounds responsible for the antiproliferative activity of the plant extract.
Moving Object Detection for Video Surveillance
Authors: Kalirajan K. , Sudha M.
Published: March 2015

The emergence of video surveillance is the most promising solution for people living independently in their home. Recently several contributions for video surveillance have been proposed. However, a robust video surveillance algorithm is still a challenging task because of illumination changes, rapid variations in target appearance, similar nontarget objects in background, and occlusions. In this paper, a novel approach of object detection for video surveillance is presented. The proposed algorithm consists of various steps including video compression, object detection, and object localization. In video compression, the input video frames are compressed with the help of two‐dimensional discrete cosine transform (2D DCT) to achieve less storage requirements. In object detection, key feature points are detected by computing the statistical correlation and the matching feature points are classified into foreground and background based on the Bayesian rule. Finally, the foreground feature points are localized in successive video frames by embedding the maximum likelihood feature points over the input video frames. Various frame based surveillance metrics are employed to evaluate the proposed approach. Experimental results and comparative study clearly depict the effectiveness of the proposed approach.
p53 Family Members Regulate Phenotypic Response to Aurora Kinase A Inhibition in Triple-Negative Breast Cancer
Authors: Tentler John J. , Ionkina Anastasia A. , Tan Aik Choon , Newton Timothy P. , Pitts Todd M. , Glogowska Magdalena J. , Kabos Peter , Sartorius Carol A. , Sullivan Kelly D. , Espinosa Joaquin M. , Eckhardt S. Gail , Diamond Jennifer R.
Published: March 2015

Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis. Advances in the treatment of TNBC have been hampered by the lack of novel effective targeted therapies. The primary goal of this study was to evaluate the efficacy of targeting Aurora kinase A (AurA), a key regulator of mitosis, in TNBC models. A secondary objective was to determine the role of the p53 family of transcriptional regulators, commonly mutated in TNBC, in determining the phenotypic response to the AurA inhibitor alisertib (MLN8237). Alisertib exhibited potent antiproliferative and proapoptotic activity in a subset of TNBC models. The induction of apoptosis in response to alisertib exposure was dependent on p53 and p73 activity. In the absence of functional p53 or p73, there was a shift in the phenotypic response following alisertib exposure from apoptosis to cellular senescence. In addition, senescence was observed in patient-derived tumor xenografts with acquired resistance to alisertib treatment. AurA inhibitors are a promising class of novel therapeutics in TNBC. The role of p53 and p73 in mediating the phenotypic response to antimitotic agents in TNBC may be harnessed to develop an effective biomarker selection strategy in this difficult to target disease. Mol Cancer Ther; 14(5); 1117–29. ©2015 AACR.
Anti–miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation
Authors: Wagenaar Timothy R. , Zabludoff Sonya , Ahn Sung-Min , Allerson Charles , Arlt Heike , Baffa Raffaele , Cao Hui , Davis Scott , Garcia-Echeverria Carlos , Gaur Rajula , Huang Shih-Min A. , Jiang Lan , Kim Deokhoon , Metz-Weidmann Christiane , Pavlicek Adam , Pollard Jack , Reeves Jason , Rocnik Jennifer L. , Scheidler Sabine , Shi Chaomei , Sun Fangxian , Tolstykh Tatiana , Weber William , Winter Christopher , Yu Eunsil , Yu Qunyan , Zheng Gang , Wiederschain Dmitri
Published: March 2015

Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti–miR-21, but not with a mismatch control anti-miRNA, resulted in significant derepression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis, and necrosis was noted in anti–miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21 suppression, global gene expression profiling was performed on anti–miR-21-treated liver cancer cells, which revealed striking enrichment in miR-21 target genes and deregulation of multiple growth-promoting pathways. Finally, in vivo dependency on miR-21 was observed in two separate HCC tumor xenograft models. In summary, these data establish a clear role for miR-21 in the maintenance of tumorigenic phenotype in HCC in vitro and in vivo.

Implications: miR-21 is important for the maintenance of the tumorigenic phenotype of HCC and represents a target for pharmacologic intervention. Mol Cancer Res; 13(6); 1009–21. ©2015 AACR.
Relaxin-2 Does Not Ameliorate Nephropathy in an Experimental Model of Type-1 Diabetes
Authors: Dschietzig Thomas Bernd , Krause-Relle Katharina , Hennequin Maud , von Websky Karoline , Rahnenführer Jan , Ruppert Jana , Grön Hans Jürgen , Armbruster Franz Paul , Bathgate Ross A. D. , Aschenbach Joerg R. , Forssmann Wolf-Georg , Hocher Berthold
Published: March 2015

Background/Aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide - is a candidate drug for both. Methods: Low-dose (32 µg/kg/day) and high-dose (320 µg/kg/day) Rlx were tested against vehicle (n = 20 each) and non-diabetic controls (n = 14) for 12 weeks in a model of type-1 diabetes induced in endothelial nitric oxide synthase knock-out (eNOS-KO) mice by intraperitoneal injection of streptozotocin. Results: Diabetic animals showed normal plasma creatinine, markedly increased albuminuria and urinary malonyldialdehyde, elevated relative kidney weight, glomerulosclerosis, and increased glomerular size, but no relevant interstitial fibrosis. Neither dose of Rlx affected these changes although the drug was active and targeted plasma levels were achieved. Of note, we found no activation of the renal TGF-β pathway in this model. In the hearts of diabetic animals, no fibrotic alterations indicative of DC could be determined which precluded testing of the initial hypothesis. Conclusions: We investigated a model showing early DN without overt tubulo-interstitial fibrosis and activation of the TGF-β-Smad-2/3 pathway. In this model, Rlx proved ineffective; however, the same may not apply to other models and types of diabetes.
Is Chemoradiotherapy Beneficial for Stage IV Rectal Cancer?
Authors: Huh Jung Wook , Kim Hee Cheol , Park Hee Chul , Choi Doo Ho , Park Joon Oh , Park Young Suk , Park Yoon Ah , Cho Yong Beom , Yun Seong Hyeon , Lee Woo Yong , Chun Ho-Kyung
Published: March 2015

Purpose: The aim of this study was to investigate the oncologic impact of preoperative or postoperative chemoradiotherapy on stage IV rectal cancer. Methods: A total of 140 consecutive patients with locally advanced mid-to-lower rectal cancer and resectable stage IV disease were prospectively enrolled. In total, 69 patients received chemoradiotherapy (26 preoperatively and 43 postoperatively); in contrast, 71 did not. Survival curves were constructed using the Kaplan-Meier method, and a multivariate analysis was performed to identify independent prognostic factors. Results: According to the multivariate analysis, radiation therapy was not an independent factor associated with either survival or recurrence. The overall survival curves revealed that patients who underwent radiotherapy tended to have a better survival compared with patients who did not undergo radiotherapy; however, this trend was not statistically significant (p = 0.057). The disease-free, local recurrence-free, and distant metastasis-free survival curves did not differ significantly between the two groups. The local recurrence-free survival rates for patients who underwent preoperative radiotherapy were significantly higher than those for patients who underwent postoperative radiotherapy (p = 0.042). Conclusion: Preoperative radiotherapy, rather than postoperative radiotherapy, may improve local control of stage IV rectal cancer. However, chemoradiotherapy did not improve the survival of patients with stage IV rectal cancer in this study.
L-Tryptophan as a Novel Potential Pharmacological Treatment for Wound Healing via Aryl Hydrocarbon Receptor Activation
Authors: Barouti Neda , Mainetti Carlo , Fontao Lionel , Sorg Olivier
Published: March 2015

Background: The aryl hydrocarbon receptor has been shown to be involved in wound healing. Objective: The aim of this study was to assess the effect of tryptophan on wound healing in vitro and in a clinical trial. Methods: The ability of tryptophan and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to increase wound healing was assessed in an in vitro scratch wound model in human keratinocytes. Topical tryptophan and vehicle were assessed for 12 weeks in 51 patients with lower limb ulcers that were resistant to conventional therapies. Results: TCDD 0.1 nM and tryptophan 1 µM increased the rate of scratch recovery in a culture model. Topical tryptophan induced stronger pain relief and faster re-epithelialization than its vehicle in patients with lower limb ulcers. Conclusion: Tryptophan shows promising potential as a novel topical treatment for wound healing.
Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis
Authors: De Frène Veerle , Gerris Jan , Weyers Steven , Dhont Marc , Vansteelandt Stijn , Annemans Lieven , De Sutter Petra
Published: March 2015

Background: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. Methods: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. Results: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). Conclusion: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.
MiR-301a Mediates the Effect of IL-6 on the AKT/GSK Pathway and Hepatic Glycogenesis by Regulating PTEN Expression
Authors: Dou Lin , Wang Shuyue , Sui Xiaofang , Meng Xiangyu , Shen Tao , Huang Xiuqing , Guo Jun , Fang Weiwei , Man Yong , Xi Jianzhong , Li Jian
Published: March 2015

Background/Aims: IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown. Methods: The activation of AKT/GSK pathway and the level of glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance. Results: In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic glycogenesis. Conclusion: We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.
Plasma Phosphatidylcholine Alterations in Cystic Fibrosis Patients: Impaired Metabolism and Correlation with Lung Function and Inflammation
Authors: Grothe Judith , Riethmüller Joachim , Tschürtz Sandra M. , Raith Marco , Pynn Chris J. , Stoll Dieter , Bernhard Wolfgang
Published: March 2015

Background: Liver impairment, ranging from steatosis to cirrhosis, is frequent in cystic fibrosis (CF) patients and is becoming increasingly significant due to their improved life expectancy. One aspect of hepatic alterations is caused by increased fecal loss of the essential nutrient choline, following enterohepatic bile phosphatidylcholine (PC) cycle impairment. Hepatic PC synthesis, both de novo and via phosphatidylethanolamine-N-methyl-transferase (PEMT), is essential for very low-density lipoprotein (VLDL) secretion. VLDL-PC in particular contributes to the organism's supply with polyunsaturated fatty acids (LC-PUFA), namely arachidonic (C20:4) and docosahexaenoic acid (C22:6). Consequently, choline deprivation and altered hepatic PC metabolism may affect plasma PC homeostasis and extrahepatic organ function. Objectives: To investigate relationships between altered plasma choline and PC homeostasis and markers of lung function and inflammation in CF. To assess alterations in hepatic choline and PC metabolism of CF patients. Design: Quantification of plasma/serum choline and PC species in adult CF patients compared to controls. Correlation of PC with forced expiratory vital capacity (FEV1) and interleukin 6 (IL-6) concentrations. Analysis of choline and PC metabolism in CF compared to controls, using deuterated choline ([D9-methyl]-choline) labeling in vivo. Results: Mean choline and PC concentrations in CF patients were lower than in controls. Choline and PC concentrations as well as fractions of C22:6-PC and C20:4-PC correlated directly with FEV1, but inversely with IL-6. Plasma concentrations of deuterated PC were decreased for both pathways, whereas only in PC synthesized via PEMT precursor enrichment was decreased. Conclusion: In CF patients, hepatic and plasma homeostasis of choline and PC correlate with lung function and inflammation. Impaired hepatic PC metabolism, exemplarily shown in three CF patients, provides an explanation for such correlations. Larger studies are required to understand the link between hepatic PC metabolism and overall clinical performance of CF patients, and the perspective of choline substitution of these patients.
TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma
Authors: Wu Huaxing , Wang Guonian , Li Shuai , Zhang Mingyue , Li Hulun , Wang Kun
Published: March 2015

Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.
Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats
Authors: Wang Rui-Xing , He Rui-Lan , Jiao Hai-Xia , Dai Mao , Mu Yun-Ping , Hu Ying , Wu Zhi-Juan , Sham James S.K. , Lin Mo-Jun
Published: March 2015

Background: Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT)-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1) induced contraction of pulmonary arteries (PAs) and store-operated Ca2+ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMCs) from chronic hypoxia (CH) and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA)-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.
For the Benefit of Others: Reasons Why Women with Breast Cancer Participate in RCTs
Authors: Jenkins Valerie A. , Fallowfield Lesley J.
Published: March 2015

Background: Appreciation of the barriers and drivers affecting enrolment in randomised clinical trials (RCTs) is important for future trial design, communication and information provision. Methods: As part of an intervention to facilitate UK multidisciplinary team communication about RCTs, women with breast cancer who discussed trials with doctors or research nurses completed questionnaires examining i) clarity of trial information and ii) reasons for their trial decision. Results: 152 women completed the questionnaires; 113/152 (74%) consented to RCT enrolment. Patients' satisfaction with communication about the trial information was very good, irrespective of participation decisions. Acceptors' and decliners' responses to 9/16 statements concerning decisions about trial participation differed significantly. ‘Wanting to help with doctor's research' influenced 100% acceptors compared to 57% of decliners (p < 0.001). Decliners were more likely to be ‘worried about randomisation' (20 vs. 39%; p < 0.035) and to ‘want doctor to choose treatment rather than be randomised' (31 vs. 53%; p < 0.031). Primary reason for trial acceptance was altruism; ‘I feel that others with my illness will benefit from the results of the trial', 58/108 (54%). Conclusion: A majority of women accepted RCT entry citing altruistic motivations as the primary driver for participation. Trial design and setting (metastatic or adjuvant) had little impact on participation.
Breast Cancer Risks and Risk Prediction Models
Authors: Engel Christoph , Fischer Christine
Published: March 2015

BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.
Impact of Karyotype Organization on Interlocus Recombination between T Cell Receptor Genes in Equidae
Authors: Drbalova Jitka , Musilova Petra , Kubickova Svatava , Sebestova Hana , Vahala Jiri , Rubes Jiri
Published: March 2015

The T cell receptor (TCR) genes (TRA, TRB, TRD and TRG) reside in 3 different chromosomal regions. During the maturation of T lymphocytes, the TCR genes are rearranged by site-specific recombination, a process that also predisposes T cells to aberrant rearrangements. Illegitimate recombination between the TCR genes occurs at a low level in healthy individuals, but this frequency may correlate with the risk of lymphoma. The aim of this work was to investigate interlocus recombination in equids. Illegitimate rearrangements were studied in peripheral blood lymphocytes by FISH with painting and BAC probes and by sequencing of PCR products, and the frequencies of recombination were assessed in horses and 4 other equids. The presence of several trans-rearrangement products between the TRA and TRG genes was verified by PCR in all investigated equids. Frequencies of trans-rearrangements in horses are higher than in humans, and colocalization of the TCR genes on the same chromosome increases the incidence of trans-rearrangements between them. The orientation of the TCR genes does not impact interlocus recombination itself but does affect the viability of cells carrying its products and consequently the number of trans-rearrangements observed in lymphocytes.
Genotype/Phenotype Correlations in Patients with Hereditary Breast Cancer
Authors: Wittersheim Maike , Büttner Reinhard , Markiefka Birgid
Published: March 2015

Of all breast cancer cases, 5-10% can be attributed to germline mutations, and the high-susceptibility genes BRCA1 and BRCA2 account for about 25-28% of these cases. For the remainder, several genes of moderate and low penetrance have been discovered. Histopathologic characteristics have been studied in small cohorts, but for most of the known non-BRCA1/2-associated hereditary breast cancers, the histologic and immunohistochemical phenotypes are not yet identified. Particularly BRCA1 tumors are associated with a distinct morphology and immunohistochemical characteristics that differ from sporadic breast cancer of age-matched controls. The recognition of features characteristic of these mutations can be helpful to identify patients likely to carry a germline mutation and to assess which gene should be screened for first, in families with a high occurrence of breast and ovarian cancer.
Formation of Abnormal Fistula on Arteriovenous Fistula in a Patient with Buttonhole Cannulation: A Case Report
Authors: Cao Wen , Chen Lin , Shi Mei , Zhou Li , Fu Ping
Published: March 2015

Buttonhole cannulation has been suggested as a technique that may lead to a reduction in many complications when compared with other techniques such as rope-ladder cannulation. Despite all above, some complications still continue, which may lead to a dysfunction of the arteriovenous fistula (AVF) and inadequate dialysis, having an impact on the quality of life of the patients or eventually making the vascular access unusable. We report a 47-year-old Chinese male with end-stage renal disease who had maintenance hemodialysis three times a week for 5 years. The AVF on the left wrist was operated 5 years ago and proved to be functionally effective with some monitoring and surveillance measures in the fourth year of hemodialysis. Two months later, the buttonhole cannulation technique was applied due to fistula punctuation difficulty by previous aneurysmal dilatation. After 10 times of buttonhole cannulation, the edema on the left forearm of the patient indicated a dysfunction of the AVF. This was further confirmed by the HD02 hemodialysis monitor and a vascular ultrasound, revealing a recirculation of 87%, an abnormal fistula between the AVF and the vein together with thrombus, and aneurysmal dilatation near the anastomosis. The site of cannulation was changed to avoid heavy recirculation (reduced to 25%), and a new AVF on the left wrist was successfully operated. Abnormal fistula on the AVF and vein during buttonhole cannulation is rarely reported, which reminds us that vascular access surveillance should be done regularly before and during the process of construction to find a possible dysfunction of the AVF in patients undergoing buttonhole cannulation.
Perfect Storm
Authors: Alcántara Carmela , Muntner Paul , Edmondson Donald , Safford Monika M. , Redmond Nicole , Colantonio Lisandro D. , Davidson Karina W.
Published: March 2015

Background—

Depression and stress have each been found to be associated with poor prognosis in patients with coronary heart disease. A recently offered psychosocial perfect storm conceptual model hypothesizes amplified risk will occur in those with concurrent stress and depressive symptoms. We tested this hypothesis in a large sample of US adults with coronary heart disease.

Methods and Results—

Participants included 4487 adults with coronary heart disease from the REasons for Geographic and Racial Differences in Stroke study, a prospective cohort study of 30 239 black and white adults. We conducted Cox proportional hazards regression with the composite outcome of myocardial infarction or death and adjustment for demographic, clinical, and behavioral factors. Overall, 6.1% reported concurrent high stress and high depressive symptoms at baseline. During a median 5.95 years of follow-up, 1337 events occurred. In the first 2.5 years of follow-up, participants with concurrent high stress and high depressive symptoms had increased risk for myocardial infarction or death (adjusted hazard ratio, 1.48 [95% confidence interval, 1.08–2.02]) relative to those with low stress and low depressive symptoms. Those with low stress and high depressive symptoms (hazard ratio, 0.92 [95% confidence interval, 0.66–1.28]) or high stress and low depressive symptoms (hazard ratio, 0.86 [95% confidence interval, 0.57–1.29]) were not at increased risk. The association on myocardial infarction or death was not significant after the initial 2.5 years of follow-up (hazard ratio, 0.89 [95% confidence interval, 0.65–1.22]).

Conclusions—

Our results provide initial support for a psychosocial perfect storm conceptual model; the confluence of depressive symptoms and stress on medical prognosis in adults with coronary heart disease may be particularly destructive in the shorter term.
Decision-Making for Destination Therapy Left Ventricular Assist Devices
Authors: McIlvennan Colleen K. , Jones Jacqueline , Allen Larry A. , Lindenfeld JoAnn , Swetz Keith M. , Nowels Carolyn , Matlock Daniel D.
Published: March 2015

Background—

Implanting centers often require the identification of a dedicated caregiver before destination therapy left ventricular assist device (DT LVAD) implantation; however, the caregiver experience surrounding this difficult decision is relatively unexplored.

Methods and Results—

From October 2012 through July 2013, we conducted semistructured, in-depth interviews with caregivers of patients considering DT LVAD. Data were analyzed using a mixed inductive and deductive approach. We interviewed 17 caregivers: 10 caregivers of patients living with DT LVAD, 6 caregivers of patients who had died with DT LVAD, and 1 caregiver of a patient who had declined DT LVAD. The themes identified, which could also be considered dialectical tensions, are broadly interpreted under 3 domains mapping to decision context, process, and outcome: (1) the stark decision context, with tension between hope and reality; (2) the challenging decision process, with tension between wanting loved ones to live and wanting to respect loved ones’ wishes; and (3) the downstream decision outcome, with tension between gratitude and burden.

Conclusions—

Decision-making surrounding DT LVAD should incorporate decision support for patients and caregivers. This should include a focus on caregiver burden and the predictable tensions that caregivers experience.
East Asian Variant of Aldehyde Dehydrogenase 2 Is Associated With Coronary Spastic Angina
Authors: Mizuno Yuji , Harada Eisaku , Morita Sumio , Kinoshita Kenji , Hayashida Mariko , Shono Makoto , Morikawa Yoshinobu , Murohara Toyoaki , Nakayama Masafumi , Yoshimura Michihiro , Yasue Hirofumi
Published: March 2015

Background—

Coronary spastic angina (CSA) is a common disease among East Asians, including Japanese. The prevalence of alcohol flushing syndrome associated with deficient activity of the variant aldehyde dehydrogenase 2 (
ALDH2*2
) genotype is prevalent among East Asians. We examined whether CSA is associated with the
ALDH2*2
genotype in Japanese.

Methods and Results—

The study subjects consisted of 202 patients in whom intracoronary injection of acetylcholine was performed by angiography on suspicion of CSA (119 men and 83 women; mean age, 66.2±11.4 years). They were divided into CSA (112 patients) and control groups (90 patients).
ALDH2
genotyping was performed by the direct application of the TaqMan polymerase chain reaction system on dried whole blood. Clinical and laboratory data were examined using conventional methods. The frequencies of male sex,
ALDH2*2
genotype carriers, alcohol flushing syndrome, tobacco smoking, and the plasma level of uric acid were higher (
P
<0.001,
P
<0.001,
P
<0.001,
P
<0.001, and
P
=0.007, respectively) and the plasma high-density lipoprotein cholesterol levels were lower (
P
<0.001) in the CSA group than in the control group. The multivariable logistic regression analysis revealed that
ALDH2*2
genotype and smoking were significantly associated with CSA (
P
<0.001 and
P
=0.024, respectively).

Conclusions—

East Asian variant
ALDH2*2
genotypes and, hence, deficient ALDH2 activity were associated with CSA in Japanese. These data support further investigation of treatment targeting aldehydes for CSA.
Impaired Right Ventricular Hemodynamics Indicate Preclinical Pulmonary Hypertension in Patients With Metabolic Syndrome
Authors: Gopal Deepa M. , Santhanakrishnan Rajalakshmi , Wang Yi‐Chih , Ayalon Nir , Donohue Courtney , Rahban Youssef , Perez Alejandro J. , Downing Jill , Liang Chang‐seng , Gokce Noyan , Colucci Wilson S. , Ho Jennifer E.
Published: March 2015

Background

Metabolic disease can lead to intrinsic pulmonary hypertension in experimental models. The contributions of metabolic syndrome (MetS) and obesity to pulmonary hypertension and right ventricular dysfunction in humans remain unclear. We investigated the association of MetS and obesity with right ventricular structure and function in patients without cardiovascular disease.

Methods and Results

A total of 156 patients with MetS (mean age 44 years, 71% women, mean body mass index 40 kg/m
2
), 45 similarly obese persons without MetS, and 45 nonobese controls underwent echocardiography, including pulsed wave Doppler measurement of pulmonary artery acceleration time (
PAAT
) and ejection time. Pulmonary artery systolic pressure was estimated from
PAAT
using validated equations. MetS was associated with lower tricuspid valve e′ (right ventricular diastolic function parameter), shorter
PAAT
, shorter ejection time, and larger pulmonary artery diameter compared with controls (
P
<0.05 for all). Estimated pulmonary artery systolic pressure based on
PAAT
was 42±12 mm Hg in participants with MetS compared with 32±9 and 32±10 mm Hg in obese and nonobese controls (
P
for
ANOVA
<0.0001). After adjustment for age, sex, hypertension, diabetes, body mass index, and triglycerides, MetS remained associated with a 20‐ms–shorter
PAAT
(β=−20.4, SE=6.5,
P
=0.002 versus obese). This association persisted after accounting for left ventricular structure and function and after exclusion of participants with obstructive sleep apnea.

Conclusions

MetS is associated with abnormal right ventricular and pulmonary artery hemodynamics, as shown by shorter
PAAT
and subclinical right ventricular diastolic dysfunction. Estimated pulmonary artery systolic pressures are higher in MetS and preclinical metabolic heart disease and raise the possibility that pulmonary hypertension contributes to the pathophysiology of metabolic heart disease.
PHASES Score for Prediction of Intracranial Aneurysm Growth
Authors: Backes Daan , Vergouwen Mervyn D.I. , Tiel Groenestege Andreas T. , Bor A. Stijntje E. , Velthuis Birgitta K. , Greving Jacoba P. , Algra Ale , Wermer Marieke J.H. , van Walderveen Marianne A.A. , terBrugge Karel G. , Agid Ronit , Rinkel Gabriel J.E.
Published: March 2015

Background and Purpose—

Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth.

Methods—

In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles.

Results—

We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5–10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22–1.43). With the lowest quartile of the PHASES score (0–1) as reference, hazard ratios were for the second (PHASES 2–3) 1.07 (95% CI, 0.49–2.32), the third (PHASES 4) 2.29 (95% CI, 1.05–4.95), and the fourth quartile (PHASES 5–14) 2.85 (95% CI, 1.43–5.67).

Conclusions—

Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.
Feel between the Lines: Implied Emotion in Sentence Comprehension
Authors: Lai Vicky Tzuyin , Willems Roel M. , Hagoort Peter
Published: March 2015

This study investigated the brain regions for the comprehension of implied emotion in sentences. Participants read negative sentences without negative words, for example, “The boy fell asleep and never woke up again,” and their neutral counterparts “The boy stood up and grabbed his bag.” This kind of negative sentence allows us to examine implied emotion derived at the sentence level, without associative emotion coming from word retrieval. We found that implied emotion in sentences, relative to neutral sentences, led to activation in some emotion-related areas, including the medial prefrontal cortex, the amygdala, and the insula, as well as certain language-related areas, including the inferior frontal gyrus, which has been implicated in combinatorial processing. These results suggest that the emotional network involved in implied emotion is intricately related to the network for combinatorial processing in language, supporting the view that sentence meaning is more than simply concatenating the meanings of its lexical building blocks.
Religiosity and Personality Traits of Hispanic and Non-Hispanic Catholic Deacons
Authors: Ferrari Joseph R.
Published: March 2015

The Hispanic masculinity style may be “machismo” (dominant, distant, and unemotional) or “caballeros” (engaged, affectionate, compassionate), but is unknown among Hispanic clergy. Using a U.S. on-line survey database, Hispanic ( n = 127) and non-Hispanic ( n = 1708) Catholic deacons self-reported religiosity and personality traits. Hispanic and non-Hispanic deacons reported similar depth on religious beliefs, but non-Hispanic, compared to Hispanic, deacons claimed higher interpersonal religious commitment and a spiritual transcendence of connectedness to others. On the HEXACO-60, Hispanic, compared to non-Hispanic, deacons reported significantly higher emotional traits and lower extraversion traits. Furthermore, Hispanic deacons reported higher fearfulness and sociability and lower boldness facets, compared to non-Hispanic deacons. These results were independent of the ethnic composition of the parish community. Results suggest that Hispanic deacons may reflect “caballeros” masculinity-caring for others and sensitive to their emotional needs while socially outgoing.
Religious Objects and the Coping Process
Authors: Lundmark Mikael
Published: March 2015

This study addresses the psychological functions of physical religious objects in religious coping by presenting case studies on the use of prayer cloths. The cases are selected from a qualitative, in-depth interview study among Swedish practising Christians suffering from cancer, on religious experiences and expressions that serve in the process of coping with a life situation changed by the disease. It is argued that current psychological theories on coping and religion lack tools for understanding the role of physical religious objects in the process of religious coping. A theoretical framework that remedies this problem is suggested and applied to the case studies. The key feature of the theoretical framework is that it modifies and extends the coping theory of Kenneth Pargament by drawing on resources from object relations theory, especially the concept of “transitional object”. The results suggests that the creation and/or handling of transitional objects is a reconstructing or preserving coping method, and that prayer cloths function as transitional objects when they (a) facilitate transition/movement between the inner subjective world and the outer objective world by being charged with significance, and (b) function as a coping tool for conserving this significance.
The TIGGE Project and Its Achievements
Authors: Swinbank Richard , Kyouda Masayuki , Buchanan Piers , Froude Lizzie , Hamill Thomas M. , Hewson Tim D. , Keller Julia H. , Matsueda Mio , Methven John , Pappenberger Florian , Scheuerer Michael , Titley Helen A. , Wilson Laurence , Yamaguchi Munehiko
Published: March 2015

The International Grand Global Ensemble (TIGGE) was a major component of The Observing System Research and Predictability Experiment (THORPEX) research program, whose aim is to accelerate improvements in forecasting high-impact weather. By providing ensemble prediction data from leading operational forecast centers, TIGGE has enhanced collaboration between the research and operational meteorological communities and enabled research studies on a wide range of topics.

The paper covers the objective evaluation of the TIGGE data. For a range of forecast parameters, it is shown to be beneficial to combine ensembles from several data providers in a multimodel grand ensemble. Alternative methods to correct systematic errors, including the use of reforecast data, are also discussed.

TIGGE data have been used for a range of research studies on predictability and dynamical processes. Tropical cyclones are the most destructive weather systems in the world and are a focus of multimodel ensemble research. Their extratropical transition also has a major impact on the skill of midlatitude forecasts. We also review how TIGGE has added to our understanding of the dynamics of extratropical cyclones and storm tracks.

Although TIGGE is a research project, it has proved invaluable for the development of products for future operational forecasting. Examples include the forecasting of tropical cyclone tracks, heavy rainfall, strong winds, and flood prediction through coupling hydrological models to ensembles.

Finally, the paper considers the legacy of TIGGE. We discuss the priorities and key issues in predictability and ensemble forecasting, including the new opportunities of convective-scale ensembles, links with ensemble data assimilation methods, and extension of the range of useful forecast skill.