bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Evaluation of the Pathogenicity of Different Strains ofSchistosoma mansoni
Authors: Euzébio Antônio Aurélio , Zuim Nádia Regina Borim , Linhares Arício Xavier , Magalhães Luiz Augusto , Zanotti-Magalhães Eliana Maria
Published: November 2012

The pathogenesis of three differentSchistosoma mansonistrains from the Brazilian states of Minas Gerais (BH strain) and São Paulo (SJ and SD strains) was evaluated in experimentally infected mice. Observations of the most severe clinical cases among local patients treated (SD strain) in the city of Campinas (São Paulo, Brazil) formed the basis of this study. Mice were used as definitive hosts and were infected with cercariae fromBiomphalaria tenagophila(SJ and SD strains) andBiomphalaria glabrata(BH strains). The parameters analyzed were as follows: number ofS. mansonieggs in mice feces; number of granulomas per tissue area in liver, spleen, lungs, pancreas, and ascending colon; measurements of hepatic and intestinal granulomas; number of adult worms; and measurements of trematode eggs. The comparison among the three strains indicated that the SD strain, isolated in Campinas, presented a higher worm recovery relative to the number of penetrating cercariae. In addition, when compared to the SJ and BH strains, the SD strain demonstrated similar pathogenicity to the BH strain, with a greater quantity of granulomas in the viscera, as well as larger granulomas and eggs. Furthermore, a greater quantity of trematode eggs was also shed in the feces.
Trends in Tissue Engineering for Blood Vessels
Authors: Nemeno-Guanzon Judee Grace , Lee Soojung , Berg Johan Robert , Jo Yong Hwa , Yeo Jee Eun , Nam Bo Mi , Koh Yong-Gon , Lee Jeong Ik
Published: November 2012

Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.
Development of a New Heterogeneous Lewis Acid Catalyst for Chemoselective Tetrahydropyranylation of Different Hydroxyl Compounds
Authors: Kolahdoozan Majid , Hossaini Mahshid
Published: November 2012

Amino functionalized triazine supported on silica‐gel was prepared and characterized. This new triazine derivative was applied as a coordinating agent for aluminum chloride. This novel Lewis acid supported on heterogeneous surface was used as an effective catalyst for protection of alcohols and phenols in the presence of 3,4‐dihydro‐2H‐pyran. This catalyst can be reused without any significant loss of activity, and it protects alcohols in the presence of phenols.
Determination of Trace Amounts of Palladium in Water Samples by Graphite Furnace Atomic Absorption Spectrometry after Dispersive Liquid‐Liquid Microextraction
Authors: Jamali Mohammad Reza , Assadi Yaghoub , Rahnama Kozani Reyhaneh
Published: November 2012

A simple, rapid, and powerful microextraction technique was used for determination of palladium (II) ion in water samples using dispersive liquid‐liquid microextraction (DLLME) followed by graphite furnace atomic absorption spectrometry (GF AAS). The different variables affecting the complexation and extraction conditions such as extraction and disperser solvent type, extraction time, pH, and concentration of chelating agent were optimized. Under the optimum conditions, the calibration graph was linear in the ranges of 0.05–1 μg L−1 with detection limit of 0.02 μg L−1. The precision (RSD %) for ten replicate determination at 0.2 μg L−1 of palladium was better than 3.5% and the enrichment factor 166.5 was obtained from only 5.0 mL of sample. Under the presence of foreign ions, no significant interference was observed. Finally, accuracy and application of the method were estimated by using test samples of natural waters spiked with different amounts of palladium.
Sorption Efficiency of a New Sorbent towards Cadmium(II): Methylphosphonic Acid Grafted Polystyrene Resin
Authors: Ferrah Nacer , Abderrahim Omar , Didi Mohamed Amine , Villemin Didier
Published: November 2012

A new chelating polymeric sorbent has been developed using polystyrene resin grafted with phosphonic acid. After characterization by FTIR and elementary analysis, the new resin has been investigated in liquid‐solid extraction of cadmium(II). The results indicated that phosphonic resin could adsorb Cd(II) ion effectively from aqueous solution. The adsorption was strongly dependent on the pH of the medium and the optimum pH value level for better sorption was between 3.2 and 5.2. The influence of other analytical parameters including contact time, amount of resin, metal ion concentration, and the presence of some electrolytes was investigated. The maximum uptake capacity of Cd(II) ions was 37,9 mg·g−1 grafted resin at ambient temperature, at an initial pH value of 5.0. The overall adsorption process was best described by pseudo second‐order kinetic. When Freundlich and Langmuir isotherms were tested, the latter had a better fit with the experimental data. Furthermore, more than 92% of Cd(II) could be eluted by using 1.0 mol·L−1 HCl in one cycle.
An Integrated Genomic Screen Identifies LDHB as an Essential Gene for Triple-Negative Breast Cancer
Authors: McCleland Mark L. , Adler Adam S. , Shang Yonglei , Hunsaker Thomas , Truong Tom , Peterson David , Torres Eric , Li Li , Haley Benjamin , Stephan Jean-Philippe , Belvin Marcia , Hatzivassiliou Georgia , Blackwood Elizabeth M. , Corson Laura , Evangelista Marie , Zha Jiping , Firestein Ron
Published: November 2012

Breast cancer has been redefined into three clinically relevant subclasses: (i) estrogen/progesterone receptor positive (ER+/PR+), (ii) HER2/ERRB2 positive, and (iii) those lacking expression of all three markers (triple negative or basal-like). While targeted therapies for ER+/PR+ and HER2+ tumors have revolutionized patient treatment and increased lifespan, an urgent need exists for identifying novel targets for triple-negative breast cancers. Here, we used integrative genomic analysis to identify candidate oncogenes in triple-negative breast tumors and assess their function through loss of function screening. Using this approach, we identify lactate dehydrogenase B (LDHB), a component of glycolytic metabolism, as an essential gene in triple-negative breast cancer. Loss of LDHB abrogated cell proliferation in vitro and arrested tumor growth in fully formed tumors in vivo. We find that LDHB and other related glycolysis genes are specifically upregulated in basal-like/triple-negative breast cancers as compared with other subtypes, suggesting that these tumors are distinctly glycolytic. Consistent with this, triple-negative breast cancer cell lines were more dependent on glycolysis for growth than luminal cell lines. Finally, we find that patients with breast cancer and high LDHB expression in their tumors had a poor clinical outcome. While previous studies have focused on the ubiquitous role of LDHA in tumor metabolism and growth, our data reveal that LDHB is upregulated and required only in certain cancer genotypes. These findings suggest that targeting LDHB or other components of lactate metabolism would be of clinical benefit in triple-negative breast cancer. Cancer Res; 72(22); 5812–23. ©2012 AACR.
An Integrated Genome-Wide Approach to Discover Tumor-Specific Antigens as Potential Immunologic and Clinical Targets in Cancer
Authors: Xu Qing-Wen , Zhao Wei , Wang Yue , Sartor Maureen A. , Han Dong-Mei , Deng Jixin , Ponnala Rakesh , Yang Jiang-Ying , Zhang Qing-Yun , Liao Guo-Qing , Qu Yi-Mei , Li Lu , Liu Fang-Fang , Zhao Hong-Mei , Yin Yan-Hui , Chen Wei-Feng , Zhang Yu , Wang Xiao-Song
Published: November 2012

Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G–based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets. Cancer Res; 72(24); 6351–61. ©2012 AACR.
PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer
Authors: Badoual Cécile , Hans Stéphane , Merillon Nathalie , Van Ryswick Cordélia , Ravel Patrice , Benhamouda Nadine , Levionnois Emeline , Nizard Mevyn , Si-Mohamed Ali , Besnier Nicolas , Gey Alain , Rotem-Yehudar Rinat , Pere Hélène , Tran Thi , Guerin Coralie L. , Chauvat Anne , Dransart Estelle , Alanio Cécile , Albert Sebastien , Barry Beatrix , Sandoval Federico , Quintin-Colonna Françoise , Bruneval Patrick , Fridman Wolf H. , Lemoine Francois M. , Oudard Stephane , Johannes Ludger , Olive Daniel , Brasnu Daniel , Tartour Eric
Published: November 2012

Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3+ T cells and programmed death-1 (PD-1)+ T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1+ T cells and the levels of PD-1+ cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1+ T cells expressed activation markers and were functional after blockade of the PD-1–PD-L1 axis in vitro. Approximately 50% of PD-1+ tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1–infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. Cancer Res; 73(1); 128–38. ©2012 AACR.
Development of [11C]erlotinib Positron Emission Tomography for In Vivo Evaluation of EGF Receptor Mutational Status
Authors: Bahce Idris , Smit Egbert F. , Lubberink Mark , van der Veldt Astrid A. M. , Yaqub Maqsood , Windhorst Albert D. , Schuit Robert C. , Thunnissen Erik , Heideman Daniëlle A. M. , Postmus Pieter E. , Lammertsma Adriaan A. , Hendrikse N. Harry
Published: November 2012

Purpose: To evaluate whether, in patients with non–small cell lung carcinoma (NSCLC), tumor uptake of [11C]erlotinib can be quantified and imaged using positron emission tomography and to assess whether the level of tracer uptake corresponds with the presence of activating tumor EGF receptor (EGFR) mutations.

Experimental Design: Ten patients with NSCLCs, five with an EGFR exon 19 deletion, and five without were scanned twice (test retest) on the same day with an interval of at least 4 hours. Each scanning procedure included a low-dose computed tomographic scan, a 10-minute dynamic [15O]H2O scan, and a 1-hour dynamic [11C]erlotinib scan. Data were analyzed using full tracer kinetic modeling. EGFR expression was evaluated using immunohistochemistry.

Results: The quantitative measure of [11C]erlotinib uptake, that is, volume of distribution (VT), was significantly higher in tumors with activating mutations, that is, all with exon 19 deletions (median VT, 1.76; range, 1.25–2.93), than in those without activating mutations (median VT, 1.06; range, 0.67–1.22) for both test and retest data (P = 0.014 and P = 0.009, respectively). Good reproducibility of [11C]erlotinib VT was seen (intraclass correlation coefficient = 0.88). Intergroup differences in [11C]erlotinib uptake were not correlated with EGFR expression levels, nor tumor blood flow.

Conclusion: [11C]erlotinib VT was significantly higher in NSCLCs tumors with EGFR exon 19 deletions. Clin Cancer Res; 19(1); 183–93. ©2012 AACR.
Predictive Biomarkers of Sensitivity to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Breast Cancer Models
Authors: Diamond Jennifer R. , Eckhardt S. Gail , Tan Aik Choon , Newton Timothy P. , Selby Heather M. , Brunkow Kelsey L. , Kachaeva Maria I. , Varella-Garcia Marileila , Pitts Todd M. , Bray Mark R. , Fletcher Graham C. , Tentler John J.
Published: November 2012

Purpose: The Aurora kinases are a family of conserved serine-threonine kinases with key roles in mitotic cell division. As with other promising anticancer targets, patient selection strategies to identify a responsive subtype will likely be required for successful clinical development of Aurora kinase inhibitors. The purpose of this study was to evaluate the antitumor activity of the Aurora and angiogenic kinase inhibitor ENMD-2076 against preclinical models of breast cancer with identification of candidate predictive biomarkers.

Experimental Design: Twenty-nine breast cancer cell lines were exposed to ENMD-2076 and the effects on proliferation, apoptosis, and cell-cycle distribution were evaluated. In vitro activity was confirmed in MDA-MB-468 and MDA-MB-231 triple-negative breast cancer xenografts. Systematic gene expression analysis was used to identify up- and downregulated pathways in the sensitive and resistant cell lines, including within the triple-negative breast cancer subset.

Results: ENMD-2076 showed antiproliferative activity against breast cancer cell lines, with more robust activity against cell lines lacking estrogen receptor expression and those without increased HER2 expression. Within the triple-negative breast cancer subset, cell lines with a p53 mutation and increased p53 expression were more sensitive to the cytotoxic and proapoptotic effects of ENMD-2076 exposure than cell lines with decreased p53 expression.

Conclusions: ENMD-2076 exhibited robust anticancer activity against models of triple-negative breast cancer and the candidate predictive biomarkers identified in this study may be useful in selecting patients for Aurora kinase inhibitors in the future. Clin Cancer Res; 19(1); 291–303. ©2012 AACR.
Phase I and Clinical Pharmacology Study of Bevacizumab, Sorafenib, and Low-Dose Cyclophosphamide in Children and Young Adults with Refractory/Recurrent Solid Tumors
Authors: Navid Fariba , Baker Sharyn D. , McCarville M. Beth , Stewart Clinton F. , Billups Catherine A. , Wu Jianrong , Davidoff Andrew M. , Spunt Sheri L. , Furman Wayne L. , McGregor Lisa M. , Hu Shuiying , Panetta John C. , Turner David , Fofana Demba , Reddick Wilburn E. , Leung Wing , Santana Victor M.
Published: November 2012

Purpose: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and pharmacodynamics of sorafenib, bevacizumab, and low-dose oral cyclophosphamide in children and young adults with recurrent/refractory solid tumors.

Experimental Design: Sorafenib dose was escalated from 90 to 110 mg/m2 twice daily with fixed doses of bevacizumab at 5 mg/kg every 3 weeks and cyclophosphamide at 50 mg/m2 daily. Once sorafenib's MTD was established, bevacizumab dose was escalated. Each course was of 21 days. Pharmacokinetics and pharmacodynamics studies were conducted during the first course.

Results: Nineteen patients (11 males; median age, 9.2 years) received a median of four courses (range, 1–23). DLTs during course 1 included grade 3 rash (two), increased lipase (one), anorexia (one), and thrombus (one). With an additional 71 courses of therapy, the most common toxicities ≥ grade 3 included neutropenia (nine), lymphopenia (nine), and rashes (four). Five of 17 evaluable patients had partial tumor responses, and five had disease stabilization (>2 courses). Median day 1 cyclophosphamide apparent oral clearance was 3.13 L/h/m2. Median day 1 sorafenib apparent oral clearance was 44 and 39 mL/min/m2 at the 2 dose levels evaluated, and steady-state concentrations ranged from 1.64 to 4.8 mg/L. Inhibition of serum VEGF receptor 2 (VEGFR2) was inversely correlated with sorafenib steady-state concentrations (P = 0.019).

Conclusion: The recommended phase II doses are sorafenib, 90 mg/m2 twice daily; bevacizumab, 15 mg/kg q3 weeks; and cyclophosphamide, 50 mg/m2 once daily. This regimen is feasible with promising evidence of antitumor activity that warrants further investigation. Clin Cancer Res; 19(1); 236–46. ©2012 AACR.
Plasma Cysteine/Cystine Reduction Potential Correlates with Plasma Creatinine Levels in Chronic Kidney Disease
Authors: Rodrigues Silvia D. , Batista Giuseppe B. , Ingberman Max , Pecoits-Filho Roberto , Nakao Lia S.
Published: November 2012

Background/Aims: Oxidative stress has been considered a nontraditional risk factor for cardiovascular disease in the chronic kidney disease (CKD) population, possibly triggered by uremic toxicity. Methods: A chromatographic method with coulometric detection was adapted to directly and simultaneously determine cysteine (Cys) and cystine (Cyss) in plasma samples. Healthy subjects and CKD subjects in different stages were analyzed. The free Cys and free Cyss levels in their plasma were determined, and the reduction potential [Eh(Cyss/2Cys)] was calculated with the Nernst equation. Results: Healthy plasma presented Eh(Cyss/2Cys) of –123 ± 7 mV. Plasma Eh(Cyss/2Cys) correlated significantly with creatinine levels (p < 0.0001, r = 0.62). Conclusion: Plasma Eh(Cyss/2Cys) correlated with increased levels of plasma creatinine, supporting the view that uremia triggers oxidative stress. In addition, it may be used as a quantitative oxidative stress biomarker in uremic conditions.
Sonographic Monitoring of Midline Shift Predicts Outcome after Intracerebral Hemorrhage
Authors: Kiphuth Ines C. , Huttner Hagen B. , Breuer Lorenz , Schwab Stefan , Köhrmann Martin
Published: November 2012

Background: Spontaneous intracerebral hemorrhage (ICH) and the evolution of subsequent perihemorrhagic edema lead to midline shift (MLS), which can be assessed by transcranial duplex sonography (TDS). In this observational study, we monitored MLS with TDS in patients with supratentorial ICH up to day 14 after the ictus, and then correlated MLS with the outcome 6 months after hospital discharge. Methods: Sixty-eight patients with spontaneous ICH (volume >20 cm3) were admitted during a 1-year period between April 2009 and April 2010. Sixty-one patients fulfilled the inclusion criteria and were eligible for analysis. TDS to measure MLS was performed upon admission and then subsequently, using serial examinations in 24-hour intervals up to day 14. Statistical tests were used to determine cut-off values for functional outcome and mortality after 6 months. Results: The median National Institutes of Health Stroke Scale (NIHSS) score upon admission was 21 and the mean hematoma volume was 52 cm3. NIHSS score, functional outcome, hematoma volume and MLS were correlated in the examined patient cohort. ICH score upon admission, hematoma volume and the extent of MLS on days 1–14 were predictive of functional outcome and death. Values of MLS showed two peaks, the first between day 2 and day 5 and the second between day 12 and day 14, indicating that edema progresses not only during the acute but also during the subacute phase. Depending on the time point, an MLS of 4.5–7.5 mm or greater indicated an impending failure of conservative therapy. An MLS of 12 mm or greater at any time indicated mortality with a sensitivity of 69%, a specificity of 100% and positive and negative predictive values of 100 and 74%, respectively. Conclusions: MLS seems to be a crucial factor for outcome after ICH. Apart from the hematoma volume itself, edema adds to the intracranial pressure. To monitor MLS in early patient management after ICH, TDS is a useful noninvasive bedside alternative, avoiding increased radiation exposure and repeated transportation of critically ill patients. Cut-off values may help to reliably predict functional outcome and treatment failure in patients undergoing maximal neurointensive therapy.
Further Evidence of No Association between Spinal Muscular Atrophy and Increased Nuchal Translucency
Authors: Barone Chiara , Bianca Sebastiano
Published: November 2012

Introduction: Several authors have reported on pregnancy outcomes associated with enlarged nuchal translucency (NT) in cases of spinal muscular atrophy (SMA), and thus, thickened NT has been considered a possible early ultrasound scan sign of SMA. The purpose of our study was to evaluate the association between an increased NT and SMA in order to use an ultrasound scan of NT as a possible marker of this disorder. Material and Methods: This is a retrospective and observational study of women who had a fetus or delivered a baby with SMA following a pregnancy in which NT ultrasound has been performed. With the support of ‘Famiglie SMA’, we acquired copies of ultrasound NT measurements, molecular genetic tests confirming the SMA diagnosis in the fetus/baby, other prenatal ultrasound evaluations and informed consent. Results: Twenty-nine Italian women met the inclusion criteria and sent us the requested reports. All had a normal NT measurement for the SMA-affected fetus, with a mean of 1.8 mm (range 0.9–2.4). Discussion: This series does not confirm an association between increased NT and SMA. Fetal genetic testing for the survival motor neuron gene 1 on the basis of increased NT is not indicated in couples with no previous history of this genetic condition.
Serum Pentraxin-3 Levels Are Associated with the Severity of Metabolic Syndrome
Authors: Karakas Mehmet Fatih , Buyukkaya Eyup , Kurt Mustafa , Motor Sedat , Akcay Adnan Burak , Karakas Esra , Buyukkaya Şule , Sen Nihat
Published: November 2012

Objectives: The aim of the present study was to assess the association between the level of pentraxin-3 (PTX-3) and the severity of metabolic syndrome (MS). Subjects and Method: One hundred and two patients with MS and 101 consecutive age- and sex-matched control subjects were included in the study. The MS patients were classified into three groups based on the number of MS criteria, i.e. group 1: patients with 3 MS criteria, group 2: patients with 4 MS criteria, and group 3: patients with 5 MS criteria. Serum PTX-3 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Results: Group 1 had higher PTX-3 levels compared to the control group (0.58 ± 0.11 ng/ml vs. 0.36 ± 0.15 ng/ml, p < 0.001). PTX-3 levels were higher in group 3 than in both group 1 (0.90 ± 0.06 ng/ml vs. 0.58 ± 0.11 ng/ml, p < 0.001) and group 2 (0.90 ± 0.06 ng/ml vs. 0.63 ± 0.12 ng/ml, p < 0.001). Group 3, however, had higher hs-CRP levels than both group 1 (1.89 ± 0.45 mg/dl vs. 1.40 ± 0.44 mg/dl, p = 0.007) and group 2 (1.89 ± 0.45 mg/dl vs. 1.47 ± 0.58 mg/dl, p = 0.01). The control group had lower hs-CRP levels than group 1 (0.81 ± 0.47 mg/dl vs. 1.40 ± 0.44 mg/dl, p < 0.001) and group 2 (0.81 ± 0.47 mg/dl vs. 1.47 ± 0.58 mg/dl, p < 0.001). Serum PTX-3 levels correlated with serum hs-CRP levels (r = 0.49, p < 0.001). Conclusions: PTX-3, a novel inflammatory marker, was found to be associated with the severity of MS.
Frequency and Clinical Association of Panton-Valentine Leukocidin-Positive Staphylococcus aureus Isolates: A Study from Kuwait
Authors: AlFouzan Wadha , Al-Haddad Aneesah , Udo Edet , Mathew Bindu , Dhar Rita
Published: November 2012

Objective: This study was undertaken to determine the frequency of Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus among strains isolated in our laboratory and to study the association of PVL-positive strains with clinical disease. Materials and Methods: A total of 291 S. aureus isolates obtained from different clinical specimens from June 1, 2009, to March 31, 2010, at the Farwania Hospital Laboratory were investigated for antimicrobial susceptibility, carriage of genes for PVL, and SCCmec elements. Antimicrobial susceptibility testing was performed by standard methods. The presence of mecA genes for PVL SCCmec typing was determined by PCR. Results: Of the 291 S. aureus isolates, 89 (30.6%) were methicillin-resistant S. aureus (MRSA), whereas 202 (69.4%) were methicillin susceptible (MSSA). Genes for PVL were detected in 13 (14.6%) and 24 (12.0%) of the MRSA and MSSA isolates, respectively. The majority of the PVL-producing MRSA and MSSA were isolated from 12 (30.7%) and 19 (21.8%) cases of skin and soft tissue infections (SSTI), respectively. Although both MSSA and MRSA strains were uniformly susceptible to rifampicin, teicoplanin, and vancomycin, multidrug resistance was observed among PVL-producing and nonproducing MRSA isolates. Both MRSA types carried SCCmec type III, IV, IVc, and V genetic elements. Conclusion: This study revealed the presence of genes for PVL in both MSSA and MRSA, associated mostly with SSTI and respiratory tract infections, supporting previous observations that PVL production is widespread among S. aureus strains obtained from different clinical sources.
Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
Authors: Butler Anne M. , Yin Xiaoyan , Evans Daniel S. , Nalls Michael A. , Smith Erin N. , Tanaka Toshiko , Li Guo , Buxbaum Sarah G. , Whitsel Eric A. , Alonso Alvaro , Arking Dan E. , Benjamin Emelia J. , Berenson Gerald S. , Bis Josh C. , Chen Wei , Deo Rajat , Ellinor Patrick T. , Heckbert Susan R. , Heiss Gerardo , Hsueh Wen-Chi , Keating Brendan J. , Kerr Kathleen F. , Li Yun , Limacher Marian C. , Liu Yongmei , Lubitz Steven A. , Marciante Kristin D. , Mehra Reena , Meng Yan A. , Newman Anne B. , Newton-Cheh Christopher , North Kari E. , Palmer Cameron D. , Psaty Bruce M. , Quibrera P. Miguel , Redline Susan , Reiner Alex P. , Rotter Jerome I. , Schnabel Renate B. , Schork Nicholas J. , Singleton Andrew B. , Smith J. Gustav , Soliman Elsayed Z. , Srinivasan Sathanur R. , Zhang Zhu-ming , Zonderman Alan B. , Ferrucci Luigi , Murray Sarah S. , Evans Michele K. , Sotoodehnia Nona , Magnani Jared W. , Avery Christy L.
Published: November 2012

Background—

The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.

Methods and Results—

We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9–1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with
MEIS1, SCN5A, ARHGAP24, CAV1
, and
TBX5
to African American populations at the genome-wide significance level (
P
<5.0×10
−8
), we also identified a novel locus:
ITGA9
, located in a region previously implicated in
SCN5A
expression. The 3p21 region harboring
SCN5A
also contained 2 additional independent secondary signals influencing PR (
P
<5.0×10
−8
).

Conclusions—

This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.
The relationship between the prescription of psychotropic drugs and suicide rates in older people in England and Wales
Authors: Shah Ajit , Zhinchin Galina , Zarate-Escudero Sofia , Somyaji Manjunath
Published: November 2012

Background:

Several studies have reported an inverse correlation between general population and elderly suicide rates and antidepressant prescribing rates. Correlations between general population and elderly suicide rates and prescribing rates of other psychotropic drugs have also been reported. All studies of elderly suicide rates have used data over a decade old.

Methods:

The relationship between elderly suicide rates and prescription rates of psychotropic drugs by the broad British National Formulary (BNF) categories, for individual psychotropic drug groups within the BNF categories (e.g. SSRIs), and for individual psychotropic drugs was examined over a 12-year period (1995–2006) using Spearman’s rank correlation. All data were ascertained from the archives of the National Statistics Office.

Results:

There was an absence of significant correlations between elderly suicides rates and rates of prescriptions of psychotropic drugs in the broad BNF categories, individual psychotropic drug groups and individual psychotropic drugs.

Discussion:

The findings may be due to methodological flaws. However, if they are genuine, then the following approaches require consideration to further reduce suicide rates: (1) development of strategies to ensure continued prescription of psychotropic drugs at the current level; (2) development of strategies to improve non-pharmacological measures, including improved mental health services provision for older people, improved assessment of suicide risk, increased availability of psychosocial interventions and restricting the availability of methods of suicide; and (3) development of strategies to implement improvement in distal risk (e.g. societal socio-economic status) and protective (e.g. societal educational attainment) factors for suicide at a societal level.
Offender Perceptions of Mandated Substance Abuse Treatment
Authors: Kras Kimberly R.
Published: November 2012

Offenders with a substance abuse diagnosis are often ordered to participate in treatment. However, little is known about how offenders perceive this mandate or how the criminal justice system should be involved. The procedural justice orientation suggests that offenders who view the mandate as legitimate and useful will be more likely to comply. In-depth interviews with probationers and parolees are analyzed to explore this issue. Overall, offenders held conflicting opinions about the mandate to attend treatment. Although offenders disliked being ordered to complete drug treatment, they understood the benefit of attending as a part of their reintegration and sobriety. Offenders felt their supervising officers were fair, but their role in drug treatment was to ensure program completion. This study adds to the literature by providing insight into offender perceptions of mandated treatment and the dimensions of the offender–officer relationship. Implications for procedural justice, future research, and policy are discussed.
Local priorities, industry realities: the music quota as cultural exceptionalism
Authors: Homan Shane
Published: November 2012

This article examines cultural quota debates in the context of local music content provision in Australia and New Zealand. The commercial radio industries in both countries are examined for the different ways in which the local music industries attempt to negotiate changing perceptions of the ‘national’ in the shift from analogue to digital media environments. A call for new configurations of local media as cultural exception is made, given the profound shifts in global cultural trade and digital media spheres, where reliance upon older notions of cultural nationalism is less stable.
Texte à images, images de textes : Dieu prend-il soin des bœufs ? de Patrick Modiano et Gérard Garouste
Authors: Morris Alan
Published: November 2012

Cet article porte sur une des nouvelles les moins connues de Patrick Modiano : Dieu prend-il soin des bœufs ?, ouvrage de bibliophilie écrit en collaboration avec l’artiste Gérard Garouste. Après un court résumé de l’histoire de ce livre – variation sur le conte pour enfants traditionnel – le texte est situé dans le contexte de l’ensemble des écrits de l’auteur, afin de mettre en évidence les nombreux jeux de miroirs qui se créent. D’une part, sont mis en valeur des éléments du récit qui sont des constantes de l’imaginaire du romancier : les personnages-animaux servant de métaphores ; l’omniprésence de la Seconde guerre mondiale et de l’Holocauste ; le clin d’œil fait à l’Œdipe ; l’importance des images (contribution d’un artiste-illustrateur); les apports intertextuels. D’autre part, la spécificité de ce texte est soulignée : le fait qu’il se termine bien et sans ambiguïté, ce qui nécessite une inversion de plusieurs grands thèmes modianiens habituels. Il y a donc une concordance évidente entre la rareté de ce livre, qui est quasiment inaccessible au grand public, et la (relative) nouveauté de certains aspects de l’histoire qu’il véhicule, aspects également rares au sein de l’œuvre modianienne.
Issued by the General Staff: Doctrine Writing at British GHQ, 1917–1918
Authors: Beach Jim
Published: November 2012

This article exploits the previously unused private papers of the General Headquarters doctrine writers to examine the process by which the British Expeditionary Force’s combat doctrine was produced and the influences upon it. It also reveals SS.198, a hitherto unknown manual from the autumn of 1917, which illustrates Field Marshal Sir Douglas Haig’s influence upon doctrine writing at the time of the controversial Third Ypres offensive. It concludes that the doctrinal process raises serious questions about the notion of a consistent ‘learning curve’ within the BEF.
Another Perspective on Australian Discipline in the Great War: The Egalitarian Bargain
Authors: Rhoden Clare
Published: November 2012

Culture as an underlying factor in Australian discipline during the Great War deserves further exploration. Most accounts relate a poor disciplinary record compared with Australia’s British and Dominion allies. A new perspective, proposing a different underlying attitude to leadership and service, is offered as one element contributing to the explanation of the different attitudes to discipline. Based on the discourse in one cultural artefact, the prose literature of the war, this paper investigates how Australian egalitarian expectations contrasted with the paternal-deferential relationship between British officers and their men. Three factors in particular contributed to the Anzac attitude to discipline: the explicit egalitarian values of Australian society, the Anzac conception of the war as work rather than a crusade, and the Australians’ persistent citizen self-identity.
Effects on Resilience of Caregivers of Persons With Autism Spectrum Disorder
Authors: Bekhet Abir K. , Johnson Norah L. , Zauszniewski Jaclene A.
Published: November 2012

BACKGROUND: Approximately 2.8 million people in the United States are diagnosed with autism spectrum disorder (ASD). Family caregivers manage many aspects of their care, which is demanding, overwhelming, and can affect their mental health. OBJECTIVE: This study examined the effects of caregiver burden (risk factor) and positive cognitions (protective factors) on resourcefulness (resilience indicator) in 95 caregivers of persons with ASD. DESIGN: Descriptive, correlational, and cross-sectional. RESULTS: Positive cognitions explained 32% of the variance in resourcefulness, F(1, 93) = 44.49, p < .001, and as positive cognitions increased, caregivers’ resourcefulness increased. A substantial drop in the beta weight of caregiver burden from B = −.36 to −.04 when positive cognitions was entered the equation suggested that positive cognitions mediated the effect of caregiver burden on resourcefulness. CONCLUSION: The results support resilience theory and suggest a need for developing interventions to strengthen positive thinking among caregivers of persons with ASD.
Honor as a value in Finland, Estonia, Italy, Russia, and Switzerland
Authors: Helkama Klaus , Verkasalo Markku , Myyry Liisa , Silfver Mia , Niit Toomas , Manganelli Anna-Maria , Andreeva G. M. , Stefanenko T. G. , Dubovskaya E. M. , Tikhomandritskaya O. A. , Stetsenko Anna
Published: November 2012

Using the Schwartz Value Model as a basis, the meaning of the value item, honor (sense of honor) was explored in eight samples in Finland ( N = 1877) and in five comparable samples of 15- to 17-year-old adolescents in Estonia, Finland, Italy, Russia, and Switzerland ( N = 1788). In Finland, honor was a self-enhancement value in all age and occupational groups, although its importance varied widely. An identical pattern was found for Estonian adolescents, but for Swiss adolescents honor was both a self-enhancement and a conservation value and for Italian and Russian adolescents, a pure conservation value. Male adolescents had higher regard for honor than female adolescents in Finland, Russia, and Switzerland, but no sex differences were found in Estonia, Italy or in the Finnish adult samples. In all adolescent samples, honor was associated with work-related values (e.g., hard work, conscientiousness).
Gender specific honor codes and cultural change
Authors: Cihangir Sezgin
Published: November 2012

The current research investigates two main goals. First, it investigates the cultural and gender differences in gender specific honor codes among youth ( N =482) from cultures with a high orientation on honor (Moroccan vs. Turkish) compared to youth from a culture with a low orientation on honor (native Dutch). Second, the current research investigates the cultural change in values underlying honor codes. Before an educational program, a pre-training test assessed the perceived determinants (i.e., religion, culture, parents and other close relatives, and friends and peers) of honor. Furthermore, the perceived importance of sexual purity of female and male family members for honor, and the perceived responsibility for the sexual purity of female family members were assessed. In addition, the current study also investigated whether students from cultures with a high orientation on honor vs. cultures with a low orientation on honor are able to indicate different types of violence as honor related, and to what extent they endorse violence against themselves when they would violate their family honor. The results of the current study shows that cultural change in cultural beliefs and attitudes underlying honor is possible through educational programs. The implications of the findings are discussed.
The damage control sequence in the elderly: Strategy, complexities, and outcomes
Authors: Newell Mark A , Skarupa David J , Rotondo Michael F
Published: November 2012

Traditional management in cases of exsanguinating abdominal trauma led to poor outcomes in critically injured patients. Because prolonged operations were not well tolerated due to the severe physiologic derangements, an abbreviated laparotomy began to be used. Patients were then resuscitated in the intensive care unit and brought back to the operating room once their physiology had been normalised. This approach has been termed the damage control sequence. Elderly trauma patients are susceptible to significant injury that may mandate a damage control sequence. For myriad reasons, including pre-existing medical conditions, decreased physiologic reserve, and the emergent nature of their injuries, the application of this management approach in the elderly is fraught with challenges. The purpose of this review is to enumerate the damage control sequence, describe the complexities of its use in the elderly, and discuss associated outcomes in this challenging patient population.
M&A and the profile of inventive activity
Authors: Valentini Giovanni , Di Guardo Maria Chiara
Published: November 2012

This article examines the effect of mergers and acquisitions (M&A) on the profile of merging firms’ inventive activity. The authors conceive of the inventive process as a recombinant search, whose outcome can be characterized along two complementary dimensions, which define its profile: its depth of impact on subsequent inventions, and its breadth of impact across different scientific domains. The profile of firms’ inventive activity depends on two main factors: the resources available to be recombined and the organizational incentives that guide the recombination process. In turn, these factors significantly depend on the upstream, technological resources available and on firms’ downstream, product-market related assets. Importantly, both of these factors may change in the aftermath of M&A, as their specific institutional features facilitate the exchange and redeployment of upstream and downstream resources. The authors then discuss how variations in the profile of firms’ inventive activity in the aftermath of an M&A reflect the diversity of upstream and downstream resources redeployed by the M&A deal. They test their hypotheses with a panel of firms from the US medical devices and photographic equipment industry. The study finds that diversity in merging firms’ downstream resources exerts a positive impact on post-acquisition profile of inventive activities, whereas diversity in knowledge bases does not seem to exert a significant direct effect on the two qualitative dimensions of inventive activity considered. Yet, technological diversity displays a positive effect in deals characterized by high market relatedness.
Exploring structural embeddedness of product market activities and resources within business units
Authors: Karim Samina
Published: November 2012

This article explores the concept of structural embeddedness and proposes a construct, contextual links, which represent coordination mechanisms applied to activities that may embed activities and their underlying resources within their business units. The main argument is that if activities and resources are highly embedded in unit structures, then unit reconfiguration should have an impact on activity reconfiguration, where reconfiguration refers to movement within the firm and retention or deletion from the firm. Specifically, the article argues that if there is a significant structural embeddedness, then removal from the contextual environment within which activities reside will result in their creating less value. Theoretical support is drawn from the dynamic capabilities and organization design literatures. Activity movements are specified as default, linked, or unlinked changes. The article examines, empirically, the simultaneous effects of activity and unit reconfiguration on activity retention to gain insight on structural embeddedness. It contrasts activity-level and unit-level contextual links; whereas the former refers to activities embedded in units, the latter refers to units embedded in the firm. Findings reveal that preserving activity-level contextual links is more influential than preserving unit-level contextual links in determining value creation from activities and their resources.
TLR4- and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T cell–independent isotype switch in mice
Authors: Pihlgren Maria , Silva Alberto B. , Madani Rime , Giriens Valérie , Waeckerle-Men Ying , Fettelschoss Antonia , Hickman David T. , López-Deber María Pilar , Ndao Dorin Mlaki , Vukicevic Marija , Buccarello Anna Lucia , Gafner Valérie , Chuard Nathalie , Reis Pedro , Piorkowska Kasia , Pfeifer Andrea , Kündig Thomas M. , Muhs Andreas , Johansen Pål
Published: November 2012

Immunoglobulin class switching from IgM to IgG in response to peptides is generally T cell–dependent and vaccination in T cell–deficient individuals is inefficient. We show that a vaccine consisting of a dense array of peptides on liposomes induced peptide-specific IgG responses totally independent of T-cell help. Independency was confirmed in mice lacking T cells and in mice deficient for MHC class II, CD40L, and CD28. The IgG titers were high, long-lived, and comparable with titers obtained in wild-type animals, and the antibody response was associated with germinal center formation, expression of activation-induced cytidine deaminase, and affinity maturation. The T cell–independent (TI) IgG response was strictly dependent on ligation of TLR4 receptors on B cells, and concomitant TLR4 and cognate B-cell receptor stimulation was required on a single-cell level. Surprisingly, the IgG class switch was mediated by TIR-domain-containing adapter inducing interferon-β (TRIF), but not by MyD88. This study demonstrates that peptides can induce TI isotype switching when antigen and TLR ligand are assembled and appropriately presented directly to B lymphocytes. A TI vaccine could enable efficient prophylactic and therapeutic vaccination of patients with T-cell deficiencies and find application in diseases where induction of T-cell responses contraindicates vaccination, for example, in Alzheimer disease.
Antibacterial effect of microvesicles released from human neutrophilic granulocytes
Authors: Timár Csaba I. , Lőrincz Ákos M. , Csépányi-Kömi Roland , Vályi-Nagy Anna , Nagy György , Buzás Edit I. , Iványi Zsolt , Kittel Ágnes , Powell David W. , McLeish Kenneth R. , Ligeti Erzsébet
Published: November 2012

Cell-derived vesicles represent a recently discovered mechanism for intercellular communication. We investigated their potential role in interaction of microbes with host organisms. We provide evidence that different stimuli induced isolated neutrophilic granulocytes to release microvesicles with different biologic properties. Only opsonized particles initiated the formation of microvesicles that were able to impair bacterial growth. The antibacterial effect of neutrophil-derived microvesicles was independent of production of toxic oxygen metabolites and opsonization or engulfment of the microbes, but depended on β2 integrin function, continuous actin remodeling, and on the glucose supply. Neutrophil-derived microvesicles were detected in the serum of healthy donors, and their number was significantly increased in the serum of bacteremic patients. We propose a new extracellular mechanism to restrict bacterial growth and dissemination.