bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-priority cognizant regression testing
Authors: Bhasin Harsh
Published: June 2014

Any change in software requires all the test cases, developed earlier, to be re-executed. This is done to make sure that the changes have not affected the proper working of the software. Since it is usually impossible to re-run all the test cases, the number of test cases, to be reexecuted, must be reduced. Prioritization, reduction and selection are the three techniques used to accomplish the same. The basis of the prioritization of test cases can be the time of execution or the cost. A test case suite has many test cases. The sequence of test cases in a suite also plays a part in evaluating the effectiveness of a suite. Both cost and priority should be taken into account to determine the order of test suites. This work proposes a fitness function, which depends on both factors. This fitness function would decide the priority of the test cases. Since it is an optimization problem, Genetic Algorithms have been used to accomplish the task. In order to verify the technique, the test data of four testing cycles of a professional Enterprise Resource Planning System has been used.
Clone detection in UML class models using class metrics
Authors: Singh Satwinder , Kaur Raminder
Published: June 2014

This paper presents a technique to detect clones in UML class models. Class metrics (number of attributes, number of operations) of a class, class attribute names, root nodes, child nodes and class method names are compared with corresponding metrics, attribute names, root node, child nodes and method names of another class. Based on the number of matched attributes, operations and metrics, a percentage of cloning is calculated. We declare two classes as clones of each other if the matching percentage of the class metrics, class attribute names and class method names is greater than a specific threshold.
Cardiac responses to left ventricular pacing in hearts with normal electrical conduction: beneficial effect of improved filling is counteracted by dyssynchrony
Authors: Boe Espen , Russell Kristoffer , Remme Espen W. , Gjesdal Ola , Smiseth Otto A. , Skulstad Helge
Published: June 2014

Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV ( P < 0.05) and increased LVEDV ( P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum ( P < 0.01) due to an increased left-to-right transseptal pressure gradient ( P < 0.05). LV pacing, however, also induced dyssynchrony ( P < 0.05) and therefore reduced LV stroke work ( P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS.
Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?
Authors: Park Song-Young , Gifford Jayson R. , Andtbacka Robert H. I. , Trinity Joel D. , Hyngstrom John R. , Garten Ryan S. , Diakos Nikolaos A. , Ives Stephen J. , Dela Flemming , Larsen Steen , Drakos Stavros , Richardson Russell S.
Published: June 2014

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s−1·mg−1, P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·g−1·min−1, P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s−1·mg−1, P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.
Crude Extracts fromLycium barbarumSuppress SREBP-1c Expression and Prevent Diet-Induced Fatty Liver through AMPK Activation
Authors: Li Wang , Li Yan , Wang Qing , Yang Yi
Published: June 2014

Lycium barbarumpolysaccharide (LBP) is well known in traditional Chinese herbal medicine that, has beneficial effects. Previous study reported that LBP reduced blood glucose and serum lipids. However, the underlying LBP-regulating mechanisms remain largely unknown. The main purpose of this study was to investigate whether LBP prevented fatty liver through activation of adenosine monophosphate-activated protein kinase (AMPK) and suppression of sterol regulatory element-binding protein-1c (SREBP-1c). Male C57BL/6J mice were fed a low-fat diet, high-fat diet, or 100 mg/kg LBP-treatment diet for 24 weeks. HepG2 cells were treated with LBP in the presence of palmitic acid. In our study, LBP can improve body compositions and lipid metabolic profiles in high-fat diet-fed mice. Oil Red O stainingin vivoandin vitroshowed that LBP significantly reduced hepatic intracellular triacylglycerol accumulation. H&E staining also showed that LBP can attenuate liver steatosis. Hepatic genes expression profiles demonstrated that LBP can activate the phosphorylation of AMPK, suppress nuclear expression of SREBP-1c, and decrease protein and mRNA expression of lipogenic genesin vivoorin vitro. Moreover, LBP significantly elevated uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α) expression of brown adipose tissue. In summary, LBP possesses a potential novel treatment in preventing diet-induced fatty liver.
Different Angiogenic Abilities of Self-Setting Calcium Phosphate Cement Scaffolds Consisting of Different Proportions of Fibrin Glue
Authors: Xiu Jintao , Fan Junjun , Li Jie , Cui Geng , Lei Wei
Published: June 2014

To investigate the different angiogenic abilities of the self-setting calcium phosphate cement (CPC) consisting of different proportions of fibrin glue (FG), the CPC powder and the FG solution were mixed at the powder/liquid (P/L) ratios of 1 : 0.5, 1 : 1, and 1 : 2 (g/mL), respectively, and pure CPC was used as a control. After being implanted into the lumbar dorsal fascia of the rabbit, the angiogenic process was evaluated by histological examination and CD31 immunohistochemistry to detect the new blood vessels. The result of the new blood vessel showed that the P/L ratio of 1 : 1 group indicated the largest quantity of new blood vessel at 4 weeks, 8 weeks, and 12 weeks after implantation, respectively. The histological evaluation also showed the best vascular morphology in the 1 : 1 group at 4 weeks, 8 weeks, and 12 weeks after the operation, respectively. Our study indicated that the CPC-FG composite scaffold at the P/L ratio of 1 : 1  (g/mL) stimulated angiopoiesis better than any other P/L ratios and has significant potential as the bioactive material for the treatment of bone defects.
SOA-Based Model for Value-Added ITS Services Delivery
Authors: Herrera-Quintero Luis Felipe , Maciá-Pérez Francisco , Marcos-Jorquera Diego , Gilart-Iglesias Virgilio
Published: June 2014

Integration is currently a key factor in intelligent transportation systems (ITS), especially because of the ever increasing service demands originating from the ITS industry and ITS users. The current ITS landscape is made up of multiple technologies that are tightly coupled, and its interoperability is extremely low, which limits ITS services generation. Given this fact, novel information technologies (IT) based on the service-oriented architecture (SOA) paradigm have begun to introduce new ways to address this problem. The SOA paradigm allows the construction of loosely coupled distributed systems that can help to integrate the heterogeneous systems that are part of ITS. In this paper, we focus on developing an SOA-based model for integrating information technologies (IT) into ITS to achieve ITS service delivery. To develop our model, the ITS technologies and services involved were identified, catalogued, and decoupled. In doing so, we applied our SOA-based model to integrate all of the ITS technologies and services, ranging from the lowest-level technical components, such as roadside unit as a service (RSUAAS), to the most abstract ITS services that will be offered to ITS users (value-added services). To validate our model, a functionality case study that included all of the components of our model was designed.
Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China
Authors: Egner Patricia A. , Chen Jian-Guo , Zarth Adam T. , Ng Derek K. , Wang Jin-Bing , Kensler Kevin H. , Jacobson Lisa P. , Muñoz Alvaro , Johnson Jamie L. , Groopman John D. , Fahey Jed W. , Talalay Paul , Zhu Jian , Chen Tao-Yang , Qian Geng-Sun , Carmella Steven G. , Hecht Stephen S. , Kensler Thomas W.
Published: June 2014

Broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can generate the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases (GST) and other cytoprotective enzymes. A broccoli sprout–derived beverage providing daily doses of 600 μmol glucoraphanin and 40 μmol sulforaphane was evaluated for magnitude and duration of pharmacodynamic action in a 12-week randomized clinical trial. Two hundred and ninety-one study participants were recruited from the rural He-He Township, Qidong, in the Yangtze River delta region of China, an area characterized by exposures to substantial levels of airborne pollutants. Exposure to air pollution has been associated with lung cancer and cardiopulmonary diseases. Urinary excretion of the mercapturic acids of the pollutants, benzene, acrolein, and crotonaldehyde, were measured before and during the intervention using liquid chromatography tandem mass spectrometry. Rapid and sustained, statistically significant (P ≤ 0.01) increases in the levels of excretion of the glutathione-derived conjugates of benzene (61%), acrolein (23%), but not crotonaldehyde, were found in those receiving broccoli sprout beverage compared with placebo. Excretion of the benzene-derived mercapturic acid was higher in participants who were GSTT1-positive than in the null genotype, irrespective of study arm assignment. Measures of sulforaphane metabolites in urine indicated that bioavailability did not decline over the 12-week daily dosing period. Thus, intervention with broccoli sprouts enhances the detoxication of some airborne pollutants and may provide a frugal means to attenuate their associated long-term health risks. Cancer Prev Res; 7(8); 813–23. ©2014 AACR.
Defining Key Signaling Nodes and Therapeutic Biomarkers in NF1-Mutant Cancers
Authors: Malone Clare F. , Fromm Jody A. , Maertens Ophélia , DeRaedt Thomas , Ingraham Rachel , Cichowski Karen
Published: June 2014

NF1 encodes a RAS GTPase-activating protein. Accordingly, aberrant RAS activation underlies the pathogenesis of NF1-mutant cancers. Nevertheless, it is unclear which RAS pathway components represent optimal therapeutic targets. Here, we identify mTORC1 as the key PI3K effector in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. However, we find that tumor regression requires sustained inhibition of both mTORC1 and MEK. Transcriptional profiling studies were therefore used to establish a signature of effective mTORC1–MEK inhibition in vivo. We unexpectedly found that the glucose transporter GLUT1 was potently suppressed, but only when both pathways were inhibited. Moreover, unlike VHL- and LKB1-mutant cancers, reduction of 18F-FDG uptake required the suppression of both mTORC1 and MEK. Together, these studies identify optimal and suboptimal therapeutic targets in NF1-mutant malignancies and define a noninvasive means of measuring combined mTORC1–MEK inhibition in vivo, which can be readily incorporated into clinical trials.

Significance: This work demonstrates that mTORC1 and MEK are key therapeutic targets in NF1-mutant cancers and establishes a noninvasive biomarker of effective, combined target inhibition that can be evaluated in clinical trials. Cancer Discov; 4(9); 1062–73. ©2014 AACR.

This article is highlighted in the In This Issue feature, p. 973
Mechanisms That Can Promote Peripheral B-cell Lymphoma in ATM-Deficient Mice
Authors: Tepsuporn Suprawee , Hu Jiazhi , Gostissa Monica , Alt Frederick W.
Published: June 2014

The Ataxia Telangiectasia–mutated (ATM) kinase senses DNA double-strand breaks (DSB) and facilitates their repair. In humans, ATM deficiency predisposes to B- and T-cell lymphomas, but in mice it leads only to thymic lymphomas. We tested the hypothesis that increased DSB frequency at a cellular oncogene could promote B-cell lymphoma by generating ATM-deficient mice with a V(D)J recombination target (DJβ cassette) within c-myc intron 1 (“DA” mice). We also generated ATM-deficient mice carrying an Eμ-Bcl-2 transgene (AB mice) to test whether enhanced cellular survival could promote B-cell lymphomas. About 30% of DA or AB mice and nearly 100% of mice harboring the combined genotypes (DAB mice) developed mature B-cell lymphomas. In all genotypes, B-cell tumors harbored oncogenic c-myc amplification generated by breakage–fusion–bridge (BFB) from dicentric chromosomes formed through fusion of IgH V(D)J recombination–associated DSBs on chromosome 12 to sequences downstream of c-myc on chromosome 15. AB tumors demonstrate that B lineage cells harboring spontaneous DSBs leading to IgH/c-myc dicentrics are blocked from progressing to B-cell lymphomas by cellular apoptotic responses. DA and DAB tumor translocations were strictly linked to the cassette, but occurred downstream, frequently in a 6-kb region adjacent to c-myc that harbors multiple cryptic V(D)J recombination targets, suggesting that bona fide V(D)J target sequences may activate linked cryptic targets. Our findings indicate that ATM deficiency allows IgH V(D)J recombination DSBs in developing B cells to generate dicentric translocations that, via BFB cycles, lead to c-myc–activating oncogenic translocations and amplifications in mature B cells. Cancer Immunol Res; 2(9); 857–66. ©2014 AACR.
Is Alcohol Drinking Associated with Renal Impairment in the General Population of South Korea?
Authors: Kim Ha-Na , Kim Se-Hong , Song Sang-Wook
Published: June 2014

Background/Aims: We examined relationships between the average amount of daily alcohol intake, drinking patterns, and renal dysfunction among South Korean adultsaged ≥ 20 years. Methods: The analysis used data from the Korean National Health and Nutrition Examination Survey (KNHANES), a cross-sectional survey of Korean civilians, conducted from January to December 2011. In this study, a sample of 5,251 participants was analysed. Results: Compared with abstinence, the odds ratio for a decrease in estimated glomerular filtration rate (eGFR) was 0.14 (95% CI: 0.01-0.91) among heavy drinkers, and 0.42 (95% CI: 0.17-0.98) among binge drinkers and the association between the amount of mean daily alcohol intake, binge-drinking status and a likelihood of reduced eGFR value showed significant trends (p = 0.041 and p = 0.038, respectively), after adjusting for age, smoking status, amount of physical activity, morbid hypertension, diabetes, dyslipidaemia, anaemia and body mass index. There was no significant association between alcohol consumption and the urine albumin to creatinine ratio in men, or between alcohol consumption and renal dysfunction in women. Conclusions: Alcohol consumption was inversely associated with a reduction in eGFR in Korean men. However, these findings should be interpreted cautiously, given the other harmful effects related to alcohol consumption, especially heavy and binge drinking.
Effect of Oxandrolone and Timing of Oral Ethinylestradiol Initiation on Pubertal Progression, Height Velocity and Bone Maturation in the UK Turner Study
Authors: Perry Rebecca J. , Gault Emma Jane , Paterson Wendy F. , Dunger David B. , Donaldson Malcolm D.C.
Published: June 2014

Background: A UK study showed final height in Turner syndrome (TS) girls receiving growth hormone is affected by age at pubertal induction and oxandrolone (Ox). Using data from that study, we analysed the effect of timing of oral ethinylestradiol (EE2) and Ox on height velocity (HV), bone maturation and pubertal progression, and compared growth response in EE2-treated versus spontaneous puberty. Methods: Analysis of HV, bone age and pubertal stage in 92 TS girls (7-13 years) randomised to Ox (0.05 mg/kg/day; max: 2.5 mg/day) or placebo from 9 years, and EE2 (year 1: 2 µg/day; year 2: 4 µg/day; year 3: 6/8/10 µg/day × 4 months) or placebo at 12 years with EE2 at 14 years. Girls enrolled at >12.25 years received EE2 at 14 years (‘late group'). Results: Fifty-six girls were randomised to EE2 at 12 years (n = 28, 11 Ox) or 14 years (n = 28, 13 Ox); there were 19 girls in the late group (9 Ox) and 17 girls with spontaneous puberty (10 Ox). Girls receiving EE2 at 12 versus 14 years had faster bone maturation, but neither group showed acceleration. Ox increased HV without altering bone maturation or pubertal progression. Girls with spontaneous puberty had greater pubertal growth (mean PHV 8.5 cm/year; p < 0.001) and height gain (p < 0.001) than EE2-treated girls despite similar mean enrolment height SD and dysmorphology scores. Conclusion: Pubertal induction with EE2 does not replicate the acceleration observed in unaffected girls or TS girls with spontaneous puberty.
Prevention of Disease Progression with Anti-Inflammatory Therapy in Patients with HCV-Related Cirrhosis: A Markov Model
Authors: Ikeda Kenji , Kawamura Yusuke , Kobayashi Masahiro , Fukushima Taito , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Saitoh Satoshi , Suzuki Fumitaka , Suzuki Yoshiyuki , Arase Yasuji , Kumada Hiromitsu
Published: June 2014

Background: The significance of anti-inflammatory therapy has not been fully evaluated in hepatitis C virus (HCV)-related cirrhosis. Patients and Methods: We analyzed stepwise progression rates from cirrhosis to hepatocellular carcinoma (HCC) and to death using a Markov model in 1,280 patients with HCV-related cirrhosis. During the observation period, 303 patients received interferon and 736 received glycyrrhizin injections as anti-inflammatory therapy. Results: In the entire group, annual progression rates from cirrhosis to HCC and from cirrhosis to death were 6.8 and 1.9%, and the rate from HCC to death was 19.0%. When sustained virological response (SVR) or biochemical response (BR) was attained with interferon, the annual rate to HCC decreased to 2.6%. On the contrary, the progression rates to HCC and to death in the patients without SVR and BR were 7.2 and 2.0%, respectively (p < 0.0001). Continuous interferon administration significantly decreased the carcinogenesis rate to 5.5% (p = 0.0087). In the analysis of the remaining patients with high alanine transaminase of 75 IU/l or more but without interferon response or without interferon administration, glycyrrhizin injection significantly decreased annual non-progression probability (no glycyrrhizin 88.0% vs. glycyrrhizin therapy 92.3%, p = 0.00055). Conclusion: Glycyrrhizin injection therapy is useful in the prevention of disease progression in interferon-resistant or intolerant patients with HCV-related cirrhosis.
Safety and Efficacy of Oxandrolone in Growth Hormone-Treated Girls with Turner Syndrome: Evidence from Recent Studies and Recommendations for Use
Authors: Sas T.C.J. , Gault E.J. , Zeger Bardsley M. , Menke L.A. , Freriks K. , Perry R.J. , Otten B.J. , de Muinck Keizer-Schrama S.M.P.F. , Timmers H. , Wit J.M. , Ross J.L. , Donaldson M.D.C.
Published: June 2014

There has been no consensus regarding the efficacy and safety of oxandrolone (Ox) in addition to growth hormone (GH) in girls with Turner syndrome (TS), the optimal age of starting this treatment, or the optimal dose. This collaborative venture between Dutch, UK and US centers is intended to give a summary of the data from three recently published randomized, placebo-controlled, double-blind studies on the effects of Ox. The published papers from these studies were reviewed within the group of authors to reach consensus about the recommendations. The addition of Ox to GH treatment leads to an increase in adult height, on average 2.3-4.6 cm. If Ox dosages <0.06 mg/kg/day are used, side effects are modest. The most relevant safety concerns are virilization (including clitoromegaly and voice deepening) and a transient delay of breast development. We advise monitoring signs of virilization breast development and possibly blood lipids during Ox treatment, in addition to regular follow-up assessments for TS. In girls with TS who are severely short for age, in whom very short adult stature is anticipated, or in whom the growth rate is modest despite good compliance with GH, adjunctive treatment with Ox at a dosage of 0.03-0.05 mg/kg/day starting from the age of 8-10 years onwards can be considered.
A Three-Year Randomized Controlled Trial in 6-Year-Old Children on Caries-Preventive Strategies in a General Dental Practice in the Netherlands
Authors: Vermaire J.H. , Poorterman J.H.G. , van Herwijnen L. , van Loveren C.
Published: June 2014

A parallel-randomized controlled trial on caries-preventive strategies was conducted in a general dental practice with a mixed socioeconomic background patient population. The aim of this study was to test the hypothesis that, compared to regular care consisting of check-ups twice a year with professional fluoride applications and pit and fissure sealants in all permanent molars, a larger caries-preventive effect can be achieved by following a non-operative caries treatment and prevention (NOCTP) strategy or by following, in addition to regular care, an increased number of professional topical fluoride applications (IPFA). A total of 230 children (6.0 years ± 3 months of age) were randomly assigned to the two experimental groups or the control group. After 3 years, 179 participants remained in the study (54 NOCTP, 62 IPFA and 63 control). The children were examined at baseline and at 3 years by the same experienced examiner, who was blinded for the allocation of the children. Caries was scored clinically at the D3 level. Per protocol analysis revealed a mean DMFS increment after 3 years of 0.15 (95% CI -0.05 to 0.35) for NOCTP, 0.34 (95% CI 0.11 to 0.54) for IPFA and 0.47 (95% CI 0.26 to 0.68) for the control group. To account for missing data, multiple imputation was used, after which the mean DMFS increment was 0.11 (95% CI -0.05 to 0.27) for NOCTP, 0.29 (95% CI 0.11 to 0.46) for IPFA and 0.40 (95% CI 0.21 to 0.55) for the control group. Testing the differences with independent samples t test revealed a lower caries increment in the NOCTP group compared to the control group. ANCOVA was used to correct for differences in baseline dmfs, socioeconomic status and perceived dental hygiene burden. The ΔDMFS effect size between the NOCTP and the control group dropped, losing statistical significance (p = 0.06). Although the results in this study are promising, it has yet to be established in a larger study whether NOCTP has the ability to be effective in regular dental practice with a mixed socioeconomic status population.
Iron Deficiency Status Irrespective of Anemia: A Predictor of Unfavorable Outcome in Chronic Heart Failure Patients
Authors: Rangel Inês , Gonçalves Alexandra , de Sousa Carla , Leite Sérgio , Campelo Manuel , Martins Elisabete , Amorim Sandra , Moura Brenda , Silva Cardoso José , Maciel Maria Júlia
Published: June 2014

Objective: To assess the prognostic significance of iron deficiency (ID) in a chronic heart failure (CHF) outpatient population. Methods and Results: We prospectively evaluated 127 patients with stable CHF and left ventricular ejection fraction ≤45%. Clinical and analytical data as well as information regarding the occurrence of the composite endpoint of overall mortality and nonfatal cardiovascular events were assessed. Among the 127 patients enrolled [81% men, median age: 62 years (25th-75th percentile: 53-68)], 46 (36%) patients had ID. Women, patients with higher plasma brain natriuretic peptide levels (>400 pg/ml) and with right ventricular systolic dysfunction presented ID more frequently (p < 0.05 for all). At 225 ± 139 days of follow-up, the composite endpoint occurred in 15 (12%) patients. It was more frequent in ID (24 vs. 5%, p = 0.001) and anemic patients (25 vs. 8%, p = 0.014). In a Cox regression analysis, ID was associated with a higher likelihood of composite endpoint occurrence (HR 5.00, 95% CI 1.59-15.78, p = 0.006). In a multivariable analysis adjusted for clinical variables, including the presence of anemia, ID remained a significant predictor of the composite endpoint (HR 5.38, 95% CI 1.54-18.87, p = 0.009). Conclusion: In a CHF outpatient population, ID carried a higher risk of unfavorable outcome, irrespectively of the presence of anemia.
Cross-Cultural Equivalence of the Patient- and Parent-Reported Quality of Life in Short Stature Youth (QoLISSY) Questionnaire
Authors: Bullinger Monika , Quitmann Julia , Silva Neuza , Rohenkohl Anja , Chaplin John E. , DeBusk Kendra , Mimoun Emmanuelle , Feigerlova Eva , Herdman Michael , Sanz Dolores , Wollmann Hartmut , Pleil Andreas , Power Michael
Published: June 2014

Background: Testing cross-cultural equivalence of patient-reported outcomes requires sufficiently large samples per country, which is difficult to achieve in rare endocrine paediatric conditions. We describe a novel approach to cross-cultural testing of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire in five countries by sequentially taking one country out (TOCO) from the total sample and iteratively comparing the resulting psychometric performance. Methods: Development of the QoLISSY proceeded from focus group discussions through pilot testing to field testing in 268 short-statured patients and their parents. To explore cross-cultural equivalence, the iterative TOCO technique was used to examine and compare the validity, reliability, and convergence of patient and parent responses on QoLISSY in the field test dataset, and to predict QoLISSY scores from clinical, socio-demographic and psychosocial variables. Results: Validity and reliability indicators were satisfactory for each sample after iteratively omitting one country. Comparisons with the total sample revealed cross-cultural equivalence in internal consistency and construct validity for patients and parents, high inter-rater agreement and a substantial proportion of QoLISSY variance explained by predictors. Conclusion: The TOCO technique is a powerful method to overcome problems of country-specific testing of patient-reported outcome instruments. It provides an empirical support to QoLISSY's cross-cultural equivalence and is recommended for future research.
Association between Compound Heterozygous Mutations of SLC34A3 and Hypercalciuria
Authors: Abe Yuki , Nagasaki Keisuke , Watanabe Toru , Abe Tokinari , Fukami Maki
Published: June 2014

Background: Mutations in SLC34A3 have been shown to cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Patients with compound heterozygous or homozygous mutations develop skeletal lesions in addition to hypercalciuria, hypophosphatemia and/or elevated 1,25-dihydroxy vitamin D [1,25-(OH)2D] levels. Here, we report a case of hypercalciuria without skeletal lesions in a patient with compound heterozygous mutations of SLC34A3.Case Presentation: A 3-year-old girl presented with microscopic hematuria. Laboratory data revealed elevated 1,25-(OH)2D levels and serum calcium, reduced serum inorganic phosphorus and hypercalciuria. In addition, the ratio of maximal rate of renal tubular reabsorption of phosphate to glomerular filtration rate was reduced. Abdominal ultrasound revealed bilateral nephrocalcinosis. These data were consistent with HHRH, but the patient had no clinical features of rickets or any family history of skeletal disease. Genetic analysis revealed compound heterozygous mutations of c.175+1 G>A and c.1234 C>T in SLC34A3.Conclusions: This is the report of a patient with compound heterozygous mutations of SLC34A3 and normal skeletal features. Biallelic mutations in SLC34A3 can thus be associated with hypercalciuria not accompanied by rickets. Orally administered inorganic phosphate is predicted to improve symptoms in these patients, hence screening for SLC34A3 mutations should be considered in patients with hypercalciuria of unknown etiology.
Distribution and Timing of Distant Metastasis after Local Therapy in a Large Cohort of Patients with Esophageal and Esophagogastric Junction Cancer
Authors: Shiozaki Hironori , Sudo Kazuki , Xiao Lianchun , Wadhwa Roopma , Elimova Elena , Hofstetter Wayne L. , Skinner Heath D. , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Blum Mariela A. , Maru Dipen M. , Ajani Jaffer A.
Published: June 2014

Background: Patients with localized esophageal and esophagogastric junction cancer (EAC) receive chemoradiation and then surgery (trimodality, TMT) or definitive chemoradiation (bimodality, BMT). Distant metastases (DMs) are common but the details of their distribution and timing in a large cohort have not been described. Methods: 629 patients with localized EAC who had TMT or BMT were analyzed. Standard statistical methods were used to define the end points. Results: The median follow-up time was 37.2 months (interquartile range 17.8-65.0). Of 356 TMT patients, 33% (119) developed DM as their first relapse and of 273 BMT patients, 40% (109) developed DM; 91% (TMT) and 96% (BMT) of the DMs were diagnosed within 2 years of local therapy. The most common sites of DM were: lung, distant nodes, liver, peritoneal cavity, bone, brain and pleura in order of frequency. The median overall survival of TMT patients with DM was 10.2 months (95% CI 7.8-12.7) and that for BMT patients with DM was 7.8 months (95% CI 5.7-9.9). Conclusions: Following TMT or BMT, ≥33% of patients developed DMs and most of these occurred within 2 years (>90%) of local therapy. A clinical model is desirable that associates clinical parameters with a high risk for DM in TMT-eligible patients prior to surgery.
Risk Factors Associated with Lipomyelomeningocele: A Case-Control Study
Authors: Esmaeili Arash , Hanaei Sara , Fadakar Kaveh , Dadkhah Sahar , Arjipour Mahdi , Habibi Zohreh , Nejat Farideh , El Khashab Mostafa
Published: June 2014

Background: In general, it seems that both genetic and environmental factors play important roles in the induction of neural tube defects. Lipomyelomeningocele (LipoMMC) is a rather common type of closed neural tube defect, but only limited studies have investigated the potential risk factors of this anomaly. Therefore, the purpose of this case-control study was to investigate the risk factors involved in LipoMMC formation. Material and Method: Various risk factors were evaluated in 35 children between 1 month and 10 years of age with LipoMMC in a hospital-based case-control study. The 2 control arms consisted of 35 children with myelomeningocele (MMC group) and 35 children with congenital anomalies other than central nervous system problems (control group). All groups were matched for age and visited the same hospital. A structured questionnaire was used for the collection of all data, including the mothers' weight and height during pregnancy, education, reproductive history, previous abortions, and socioeconomic status, as well as the parents' consanguinity and family history of the same anomalies. Results: Univariate analysis of the children with LipoMMC compared to the control group showed that the use of periconceptional folic acid supplementation was significantly lower in the MMC and LipoMMC groups compared to the control group. In addition, comparison of the MMC and control groups revealed statistically significant differences regarding the use of folic acid and maternal obesity. In multivariate analysis, use of folic acid in the periconceptional period and during the first trimester was an independent risk factor for LipoMMC and MMC. Furthermore, maternal obesity was a significantly positive risk factor for MMC. Conclusion: The probable risk factors for LipoMMC were investigated in this case-control study. Consumption of folic acid in the periconceptional period and during the first trimester is an independent protective factor against LipoMMC. It seems that larger studies are needed to examine other possible risk factors.
Verhaltensmedizin in der Neurologie: State of the Art
Authors: Leplow Bernd
Published: June 2014

Verhaltensmedizinische Interventionen setzen bei neurologischen Erkrankungen mit dem Ziel an, die gesellschaftliche Teilhabe so weit wie möglich zu erhalten oder wiederherzustellen. Dies kann über restitutive und kompensatorische Zugangswege mit oder ohne direkte Intervention am somatischen Substrat erfolgen. So lassen sich schlaganfallbedingte Paresen zumindest teilweise auch als Verlust des motorischen Gedächtnisses erklären. Durch lernpsychologisch begründete Interventionen ist neben der funktionellen Verbesserung auch eine Wiederherstellung der somatosensorischen Repräsentation möglich. Über EEG-Feedback-gestützte Brain-Computer-Interfaces kann dagegen die bei nahezu kompletten Lähmungen der Willkürmotorik ausgefallene Kommunikation mit der Umwelt kompensiert werden. Therapeutische Maßnahmen, die nicht direkt am somatischen Substrat ansetzen, zielen entweder auf die Wechselwirkung zwischen kurzfristigen, symptomatischen Verschlechterungen und situativen Auslösern oder auf den emotionalen und behavioralen Umgang mit einer somatischen Erkrankung. So ist eine situationsspezifische Symptomkontrolle unter anderem bei Anfallserkrankungen mit oder ohne Neurofeedback-Unterstützung möglich. Darüber hinaus kann die Behandlung psychischer Beschwerden und Störungen heute bei fast allen neurologischen Erkrankungen indiziert sein. Deshalb sollen mit diesem Beitrag die vielfältigen Möglichkeiten herausgestellt werden, die bereits jetzt zur verhaltensmedizinischen Unterstützung der Selbstregulation bei ganz unterschiedlichen neurologischen Krankheitsbildern zur Verfügung stehen.
Clinical and Microbiological Evaluation of an Extended-Wear Hearing Instrument
Authors: Sim Jae Hoon , Xie Youzhou , Karamuk Erdal , von Kameke Alexander , Holder Jens Ten , Zbinden Reinhard , Röösli Christof , Huber Alexander M.
Published: June 2014

This study aimed to examine the integrity of the ear canal skin and its microbiological changes caused by an extended-wear hearing device. An extended-wear hearing device, Lyric2 (Phonak AG, Switzerland), which is the second generation of the Lyric device, was fitted to 52 ears of 27 subjects. A refit of the device was done for a selection of ears (n = 15) for which the initial fitting was interrupted (28 ears). A matching control group consisted of 10 ears of 10 subjects with no history of using any form of hearing aid for 3 months. The ear canal skin of ears fitted with the hearing device was inspected using an otoendoscope, and signs of problematic pathological conditions were graded. Microbiological examinations were performed at three different stages following fitting. Wearing the device was interrupted in 28 (53.8%) out of the 52 ears for the initial fitting, and 17 of the 28 interrupted cases (60.7%) were due to issues of the ear canal skin. In 3 of 15 ears (25%) following a refitting, wearing the device was interrupted yet again, and 1 of these 3 interruptions was caused by ear canal skin pathologies. Growth of bacteria was not enhanced or prompted by wearing the Lyric2, and Gram-negative bacteria could not be cultured while the device was in place. Based on aspects of ear canal skin pathology, continuous and nonproblematic uses of the Lyric2 device are presumed to be obtained if the fitting is done carefully. Wearing of the Lyric2 device can be considered safe from a microbiological perspective and does not promote growth of Gram-negative bacteria.
LRRC26 Is a Functional BK Channel Auxiliary γ Subunit in Arterial Smooth Muscle Cells
Authors: Evanson Kirk W. , Bannister John P. , Leo M. Dennis , Jaggar Jonathan H.
Published: June 2014

Rationale
:

Smooth muscle cell (myocyte) large-conductance calcium (Ca)
2+
-activated potassium (BK) channels are functionally significant modulators of arterial contractility. Arterial myocytes express both pore-forming BKα and auxiliary β1 subunits, which increase channel Ca
2+
sensitivity. Recently, several leucine-rich repeat containing (LRRC) proteins have been identified as auxiliary γ subunits that elevate the voltage sensitivity of recombinant and prostate adenocarcinoma BK channels. LRRC expression and physiological functions in native cell types are unclear.

Objective
:

Investigate the expression and physiological functions of leucine-rich repeat containing protein 26 (LRRC26) in arterial myocytes.

Methods and Results
:

Reverse transcription polymerase chain reaction and Western blotting detected LRRC26 mRNA and protein in cerebral artery myocytes. Biotinylation, immunofluorescence resonance energy transfer microscopy, and coimmunoprecipitation indicated that LRRC26 was located in close spatial proximity to, and associated with, plasma membrane BKα subunits. LRRC26 knockdown (RNAi) reduced total and surface LRRC26, but did not alter BKα or β1, proteins in arteries. LRRC26 knockdown did not alter Ca
2+
sparks but reduced BK channel voltage sensitivity, which decreased channel apparent Ca
2+
sensitivity and transient BK current frequency and amplitude in myocytes. LRRC26 knockdown also increased myogenic tone over a range (40–100 mm Hg) of intravascular pressures, and reduced vasoconstriction to iberiotoxin and vasodilation to NS1619, BK channel inhibitors and activators, respectively. In contrast, LRRC26 knockdown did not alter depolarization (60 mmol/L K
+
)–induced vasoconstriction.

Conclusions
:

LRRC26 is expressed, associates with BKα subunits, and elevates channel voltage- and apparent Ca
2+
sensitivity in arterial myocytes to induce vasodilation. This study indicates that arterial myocytes express a functional BK channel γ subunit.
Ambulatory Hypertension Subtypes and 24-Hour Systolic and Diastolic Blood Pressure as Distinct Outcome Predictors in 8341 Untreated People Recruited From 12 Populations
Authors: Li Yan , Wei Fang-Fei , Thijs Lutgarde , Boggia José , Asayama Kei , Hansen Tine W. , Kikuya Masahiro , Björklund-Bodegård Kristina , Ohkubo Takayoshi , Jeppesen Jørgen , Gu Yu-Mei , Torp-Pedersen Christian , Dolan Eamon , Liu Yan-Ping , Kuznetsova Tatiana , Stolarz-Skrzypek Katarzyna , Tikhonoff Valérie , Malyutina Sofia , Casiglia Edoardo , Nikitin Yuri , Lind Lars , Sandoya Edgardo , Kawecka-Jaszcz Kalina , Mena Luis , Maestre Gladys E. , Filipovský Jan , Imai Yutaka , O’Brien Eoin , Wang Ji-Guang , Staessen Jan A.
Published: June 2014

Background—

Data on risk associated with 24-hour ambulatory diastolic (DBP
24
) versus systolic (SBP
24
) blood pressure are scarce.

Methods and Results—

We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP
24
≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54;
P
≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75;
P
≤0.0054). Isolated systolic hypertension (SBP
24
≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (
P
≤0.0012). Below age 50, DBP
24
was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05;
P
=0.0039) and cardiovascular mortality (HR, 4.07;
P
=0.0032) and for all cardiovascular end points combined (HR, 1.74;
P
=0.039) with a nonsignificant contribution of SBP
24
(HR≤0.92;
P
≥0.068); above age 50, SBP
24
predicted all end points (HR≥1.19;
P
≤0.0002) with a nonsignificant contribution of DBP
24
(0.96≤HR≤1.14;
P
≥0.10). The interactions of age with SBP
24
and DBP
24
were significant for all cardiovascular and coronary events (
P
≤0.043).

Conclusions—

The risks conferred by DBP
24
and SBP
24
are age dependent. DBP
24
and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP
24
and isolated systolic and mixed hypertension are the predominant risk factors.
Dabigatran Etexilate and Risk of Myocardial Infarction, Other Cardiovascular Events, Major Bleeding, and All‐Cause Mortality: A Systematic Review and Meta‐analysis of Randomized Controlled Trials
Authors: Douxfils Jonathan , Buckinx Fanny , Mullier François , Minet Valentine , Rabenda Véronique , Reginster Jean‐Yves , Hainaut Philippe , Bruyère Olivier , Dogné Jean‐Michel
Published: June 2014

Background

Signals of an increased risk of myocardial infarction (
MI
) have been identified with dabigatran etexilate in randomized controlled trials (
RCTs
).

Methods and Resules

We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta‐analysis included all
RCT
s and the availability of outcome data for
MI
, other cardiovascular events, major bleeding, and all‐cause mortality. Among the 501 unique references identified, 14
RCT
s fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (

OR
PETO

) values using the fixed‐effect model (
FEM
) for
MI
, other cardiovascular events, major bleeding, and all‐cause mortality were 1.34 (95%
CI
1.08 to 1.65,
P
=0.007), 0.93 (95%
CI
0.83 to 1.06,
P
=0.270), 0.88 (95%
CI
0.79 to 0.99,
P
=0.029), and 0.89 (95%
CI
0.80 to 1.00,
P
=0.041). When compared with warfarin,

OR
PETO

values using
FEM
were 1.41 (95%
CI
1.11 to 1.80,
P
=0.005), 0.94 (95%
CI
0.83 to 1.06,
P
=0.293), 0.85 (95%
CI
0.76 to 0.96,
P
=0.007), and 0.90 (95%
CI
0.81 to 1.01,
P
=0.061), respectively. In
RCT
s using the 150‐mg
BID
dosage, the

OR
PETO

values using
FEM
were 1.45 (95%
CI
1.11 to 1.91,
P
=0.007), 0.95 (95%
CI
0.82 to 1.09,
P
=0.423), 0.92 (95%
CI
0.81 to 1.05,
P
=0.228), and 0.88 (95%
CI
0.78 to 1.00,
P
=0.045), respectively. The results of the 110‐mg
BID
dosage were mainly driven by the
RE
‐
LY
trial.

Conclusions

This meta‐analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of
MI
. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all‐cause mortality.
Playing Cards at the Eucharistic Table: Music, Theology, and Society in a Corpus Christi Villancico from Colonial Mexico, 1628
Authors: Cashner Andrew A.
Published: June 2014

As part of the festivities of Corpus Christi in 1628, a cathedral choir in colonial Mexico sang about the Eucharist through the metaphor of a card game. This music is a previously unstudied, fragmentary villancico, composed by Juan Gutiérrez de Padilla for the cathedral of Puebla de los Ángeles, and it opens a window into the social history of card-playing and gambling in the Spanish colonies. It stems from a broader tradition of “divinizing” cards, including poetry and drama by Lope de Vega and González de Eslava. The article explores the theological and social implications of using liturgical music to present Christ as a rogue card player, winning humanity back from the devil by laying down the trump card of his own body on the table. Includes an edition of the surviving music. The online version includes a recording played on the organ by the author.
The bats of northeastern Brazil: a panorama
Authors: Garcia Ana Cristina L. , Leal Edson S.B. , Rohde Claudia , Carvalho-Neto Francisco G. , Montes Martín A.
Published: June 2014

Due to the lack of studies with a regional focus on the richness and distribution of the fauna of chiropterans in northeastern Brazil, this paper presents a collection of these data gathered in an extensive literature review. The data analyzed include technical reports of environment consulting agencies, abstracts presented in scientific meetings, monographs, dissertations, theses, papers, scientific notes, short communications, book chapters and books on bats of South America, Brazil and the biomes Amazon, Caatinga, Cerrado and Atlantic Forest. The numbers of municipalities surveyed per biome and the localities, municipalities and species richness for each state and biome in northeastern Brazil were determined. This information indicated the regions lacking more consistent Chiroptera sampling efforts, namely large areas in the Amazon, Caatinga and Cerrado. However, bat surveys in Atlantic Forest environments in most northeastern Brazilian states were considered representative. Although bat populations in some states have been poorly surveyed, the results of this review afford to conclude that a large part of the diversity of bat species known in Brazil has been reported for the northeastern region of the country. This review enlarges the knowledge on bat species richness and distribution in northeastern Brazil, and indicates areas suffering from wide survey gaps.