bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Effect of Rho Kinase Inhibition on Calcium Signaling in Rat Isolated Large and Small Arteries
Authors: Martinsen Anneloes , Yerna Xavier , Rath Géraldine , Gomez Elvira Leon , Dessy Chantal , Morel Nicole
Published: September 2012

In addition to its role in the regulation of artery contraction, Rho kinase (ROCK) was reported to be involved in the cytosolic calcium response to vasoconstrictor agonists in rat aorta and superior mesenteric artery (SMA). However, it remains to be determined whether ROCK also contributes to calcium signaling in resistance arteries, which play a major role in blood pressure regulation. The investigation of the effect of ROCK inhibition on the calcium and contractile responses of rat resistance mesenteric artery (RMA), in comparison with aorta and SMA, indicated that the calcium response to noradrenaline was inhibited by the ROCK inhibitor Y-27632 in aorta and SMA but not in RMA. The effect of Y-27632 on the calcium signal was unaffected by cytochalasin-D. ROCK activation in noradrenaline-stimulated arteries was confirmed by the inhibition of myosin light chain phosphorylation by Y-27632. Moreover, noradrenaline-induced calcium signaling was similarly inhibited by nimodipine in aorta, SMA and RMA, but nimodipine sensitivity of the contraction increased from the aorta to the RMA, suggesting that the contraction was controlled by different sources of calcium. In pressurized RMA, Y-27632 and H-1152 depressed pressure-induced calcium responses and abolished myogenic contraction. These results stress the important differences in calcium signaling between conductance and resistance arteries.
Outcome of Trimodality-Eligible Esophagogastric Cancer Patients Who Declined Surgery after Preoperative Chemoradiation
Authors: Taketa Takashi , Correa Arlene M. , Suzuki Akihiro , Blum Mariela A. , Chien Pamela , Lee Jeffrey H. , Welsh James , Lin Steven H. , Maru Dipen M. , Erasmus Jeremy J. , Bhutani Manoop S. , Weston Brian , Rice David C. , Vaporciyan Ara A. , Hofstetter Wayne L. , Swisher Stephen G. , Ajani Jaffer A.
Published: September 2012

Background: For patients with localized esophageal cancer (EC) who can withstand surgery, the preferred therapy is chemoradiation followed by surgery (trimodality). However, after achieving a clinical complete response [clinCR; defined as both post-chemoradiation endoscopic biopsy showing no cancer and physiologic uptake by positron emission tomography (PET)], some patients decline surgery. The literature on the outcome of such patients is sparse. Method: Between 2002 and 2011, we identified 622 trimodality-eligible EC patients in our prospectively maintained databases. All patients had to be trimodality eligible and must have completed preoperative staging after chemoradiation that included repeat endoscopic biopsy and PET among other routine tests. Results: Out of 622 trimodality-eligible patients identified, 61 patients (9.8%) declined surgery. All 61 patients had a clinCR. The median age was 69 years (range 47–85). Males (85.2%) and Caucasians (88.5%) were dominant. Baseline stage was II (44.2%) or III (52.5%), and histology was adenocarcinoma (65.6%) or squamous cell carcinoma (29.5%). Forty-two patients are alive at a median follow-up of 50.9 months (95% CI 39.5–62.3). The 5-year overall and relapse-free survival rates were 58.1 ± 8.4 and 35.3 ± 7.6%, respectively. Of 13 patients with local recurrence during surveillance, 12 had successful salvage resection. Conclusion: Although the outcome of 61 EC patients with clinCR who declined surgery appears reasonable, in the absence of a validated prediction/prognosis model, surgery must be encouraged for all trimodality-eligible patients.
A Mechanistic Study of the Effect of Doxorubicin/Adriamycin on the Estrogen Response in a Breast Cancer Model
Authors: Pritchard Jessica E. , Dillon Patrick M. , Conaway Mark R. , Silva Corinne M. , Parsons Sarah J.
Published: September 2012

Objective: Estrogen treatment limits the cytotoxic effects of chemotherapy in estrogen receptor-positive (ER+) breast cancer cell lines, suggesting that estrogen pathway signaling may confer chemotherapeutic resistance. This study investigates the molecular responses of ER+ breast cancer cell lines to the chemotherapeutic agent, doxorubicin, in the presence or absence of estrogen. Methods: ER+ MCF-7 and T47-D cells were cultured in hormone-starved or estrogen-containing media with or without doxorubicin at concentrations mimicking the low concentrations seen in plasma and tumor microenvironments in humans following typical bolus administration. Protein levels, phosphorylations, and interactions of estrogen-signaling molecules were assessed following these treatments, as well the effects of ER signaling inhibitors on cell proliferation. Results: Surprisingly, estrogen and doxorubicin co-treatment markedly induced pro-growth alterations compared to doxorubicin alone and modestly enhanced estrogen alone-induced changes. Several inhibitors suppressed cell proliferation in the presence of doxorubicin and estrogen. Conclusions: These findings demonstrate that molecular changes caused by doxorubicin in ER+ breast cancer cells can be reversed by estrogen, providing molecular evidence for the poorer responses of ER+ tumors to doxorubicin in the presence of physiologic estrogen levels. Our results also suggest that the addition of drugs targeting the ER, EGFR, the SFKs, MEK, PI3K, and/or the MMP proteins to a conventional chemotherapy regimen may improve chemosensitivity.
Terminal-Restriction Fragment Length Polymorphism (T-RFLP) Analysis for Changes in the Gut Microbiota Profiles of Indomethacin- and Rebamipide-Treated Mice
Authors: Imaeda Hirotsugu , Fujimoto Takehide , Takahashi Kenichiro , Kasumi Eiji , Fujiyama Yoshihide , Andoh Akira
Published: September 2012

Background/Aims: We investigated the effects of indomethacin and rebamipide on the gut microbiota profiles using terminal restriction fragment polymorphism (T-RFLP) analysis. Materials and Methods: Female C57BL/6J mice were given indomethacin (10 mg/kg, s.c.) once a day and 2.5 mg rebamipide orally 3 times a day. After 7 days, they were sacrificed, and luminal contents were obtained from the ileum and cecum. The gut microbiota communities were analyzed by T-RFLP analysis with BslI digestion. Results: T-RFLP analyses showed that rebamipide and indomethacin had no significant effects on the gut microbiota profiles in the ileum and cecum. In contrast, the combination of rebamipide + indomethacin induced a significant change in the gut microbiota. The changes in the microbiota composition induced by the combination of rebamipide + indomethacin were characterized by the increase in the orders Bifidobacteriales and Lactobacillales, the genera Bacteroides and Prevotella and the family Clostridiaceae. The diversity of the gut microbiota community generated by the combination of rebamipide + indomethacin was significantly higher than those induced by either rebamipide or indomethacin alone. Conclusion: The combination of rebamipide + indomethacin induces remarkable changes in the gut microbiota composition and diversity. The clinical activity of rebamipide on nonsteroidal anti-inflammatory drug-induced intestinal injury may be exerted through a modulation of the gut microbiota.
Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy
Authors: Mychasiuk R. , Richards S. , Nakahashi A. , Kolb B. , Gibb R.
Published: September 2012

Autism is a highly debilitating disorder that has recently displayed a dramatic rise in incidence. In order to realistically study preventative and remedial strategies, it is important that we develop and understand useful animal models of the disorder. The purpose of this study was to investigate the efficacy of the prenatal valproic acid (VPA) rat model of autism by examining the neuro-anatomical and behavioural outcomes of offspring exposed to this paradigm. The VPA-treated rats exhibited behavioural changes in the delayed non-match-to-sample task, novel object recognition, activity box, and Whishaw tray reaching task. Anatomically, there was a reduction in brain weight and cortical thickness, along with decreased dendritic branching in the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), and decreased spine density in the mPFC, OFC, and cerebellum. Behavioural and anatomical findings from this study produced reliable results indicating that prenatal VPA exposure may be a viable model for the study of autism in rats.
Associations among Darbepoetin-α, CD34+ Cells and Cardiovascular Disease Events in Patients on Hemodialysis
Authors: Sanada Daisuke , Honda Hirokazu , Kato Noriyuki , Yokochi Akio , Michihata Tetsuo , Akizawa Tadao
Published: September 2012

Background and Objectives: Erythropoiesis-stimulating agents (ESAs) might moderate circulating CD34-positive hematopoietic stem (CD34+) cells. We assessed associations between ESA therapy and CD34+ cells and their impact on cardiovascular disease (CVD) events in patients on prevalent hemodialysis (HD). Design, Setting, Participants and Measurements: We analyzed 95 patients on prevalent HD who received the ESAs epoetin-β (n = 22), darbepoetin-α (n = 60), or neither (control; no ESA, n = 13). Baseline values for CD34+ cells, high-sensitivity C-reactive protein, interleukin-6, vascular endothelial growth factor, inter-cellular adhesion molecule-1, and carotid intima-media thickness were determined. The numbers of CD34+/erythropoietin receptor (EPOR)+ cells were determined in 35 and 8 patients in the darbepoetin-α and control groups, respectively. CD34+ cells were counted after 6 and 12 months of darbepoetin-α treatment (n = 35). All patients were followed up for a mean of 28 months. Results: Hemoglobin levels were lower, carotid intima-media thickness was more pronounced, and the ESA dose was higher in patients with a low, than with a high, CD34+ cell count. The ratio of CD34+/EPOR+ to CD34+ cells positively correlated with the darbepoetin-α dose. A low, but not a high, dose of darbepoetin-α for 6 and 12 months was associated with more CD34+ cells. Although high-dose darbepoetin-α therapy was an independent predictor of composite CVD events, this association disappeared when adjusted for the CD34+ cell count with other confounders. Conclusions: High-dose ESA therapy is associated with a low CD34+ cell count and comprises a risk factor for CVD events in patients on prevalent HD.
GLIDE: GPU-Based Linear Regression for Detection of Epistasis
Authors: Kam-Thong Tony , Azencott Chloé-Agathe , Cayton Lawrence , Pütz Benno , Altmann André , Karbalai Nazanin , Sämann Philipp G. , Schölkopf Bernhard , Müller-Myhsok Bertram , Borgwardt Karsten M.
Published: September 2012

Due to recent advances in genotyping technologies, mapping phenotypes to single loci in the genome has become a standard technique in statistical genetics. However, one-locus mapping fails to explain much of the phenotypic variance in complex traits. Here, we present GLIDE, which maps phenotypes to pairs of genetic loci and systematically searches for the epistatic interactions expected to reveal part of this missing heritability. GLIDE makes use of the computational power of consumer-grade graphics cards to detect such interactions via linear regression. This enabled us to conduct a systematic two-locus mapping study on seven disease data sets from the Wellcome Trust Case Control Consortium and on in-house hippocampal volume data in 6 h per data set, while current single CPU-based approaches require more than a year’s time to complete the same task.
Shared Copy Number Variation in Simultaneous Nephroblastoma and Neuroblastoma due to Fanconi Anemia
Authors: Serra A. , Eirich K. , Winkler A.K. , Mrasek K. , Göhring G. , Barbi G. , Cario H. , Schlegelberger B. , Royer-Pokora B. , Liehr T. , Leriche C. , Henne-Bruns D. , Barth T.F. , Schindler D.
Published: September 2012

Concurrent emergence of nephroblastoma (Wilms Tumor; WT) and neuroblastoma (NB) is rare and mostly observed in patients with severe subtypes of Fanconi anemia (FA) with or without VACTER-L association (VL). We investigated the hypothesis that early consequences of genomic instability result in shared regions with copy number variation in different precursor cells that originate distinct embryonal tumors. We observed a newborn girl with FA and VL (aplasia of the thumbs, cloacal atresia (urogenital sinus), tethered cord at L3/L4, muscular ventricular septum defect, and horseshoe-kidney with a single ureter) who simultaneously acquired an epithelial-type WT in the left portion of the kidney and a poorly differentiated adrenal NB in infancy. A novel homozygous germline frameshift mutation in PALB2 (c.1676_c1677delAAinsG) leading to protein truncation (pGln526ArgfsX1) inherited from consanguineous parents formed the genetic basis of FA-N. Spontaneous and induced chromosomal instability was detected in the majority of cells analyzed from peripheral lymphocytes, bone marrow, and cultured fibroblasts. Bone marrow cells also showed complex chromosome rearrangements consistent with the myelodysplastic syndrome at 11 months of age. Array-comparative genomic hybridization analyses of both WT and NB showed shared gains or amplifications within the chromosomal regions 11p15.5 and 17q21.31-q25.3, including genes that are reportedly implicated in tumor development such as IGF2, H19, WT2, BIRC5, and HRAS.
Morphine Metabolism in Human Skin Microsomes
Authors: Heilmann S. , Küchler S. , Schäfer-Korting M.
Published: September 2012

For patients with severe skin wounds, topically applied morphine is an option to induce efficient analgesia due to the presence of opioid receptors in the skin. However, for topical administration it is important to know whether the substance is biotransformed in the skin as this can eventually reduce the concentration of the active agent considerably. We use skin microsomes to elucidate the impact of skin metabolism on the activity of topically applied morphine. We are able to demonstrate that morphine is only glucuronidated in traces, indicating that the biotransformation in the skin can be neglected when morphine is applied topically. Hence, there is no need to take biotransformation into account when setting up the treatment regimen.
Effect of Lycopene and Tomato Products on Cholesterol Metabolism
Authors: Palozza P. , Catalano A. , Simone R.E. , Mele M.C. , Cittadini A.
Published: September 2012

Background/Aims: Increased ingestion of tomato, containing lycopene, has been associated with a decreased risk for atherosclerosis, although the exact molecular mechanism is still unknown. Here we review the available evidence for a direct regulation of tomato lycopene on cholesterol metabolism using results from experimental and human studies. Results: In human macrophages lycopene dose dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in cholesterol synthesis through a reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and expression, a modulation of low- density lipoprotein (LDL) receptor and acyl-coenzyme A:cholesterol acyltransferase activity. An increase in cholesterol efflux through an enhancement of ABCA1 and caveolin-1 expression was also observed. In animal models of atherosclerosis, lycopene and tomato products decreased plasma total cholesterol, LDL cholesterol and increased high-density lipoprotein cholesterol. In agreement with the experimental results, most human intervention trials analyzed show that dietary supplementation with lycopene and/or tomato products reduced plasma LDL cholesterol dependently on the dose and the time of administration. Conclusions: Although lycopene and tomato products seem to possess direct hypocholesterolemic properties, more experimental studies are needed to better understand the mechanisms involved. There is also a need for more well-designed human dietary intervention studies to better clarify the role of lycopene as a hypocholesterolemic agent.
Cisplatin-Docetaxel Induction plus Concurrent 3-D Conformal Radiotherapy and Weekly Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients: A Phase II Trial
Authors: Poudenx M. , Bondiau P.Y. , Chamorey E. , Venissac N. , Otto J. , Pourel N. , Castelnau O. , Tessier E. , De Surmont Salasc B. , Berdah J.F. , Pop D. , Michel C. , Mouroux J.
Published: September 2012

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study was to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m2 and cisplatin 75 mg/m2 followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m2) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). The primary endpoint was the response rate. Secondary objectives were toxicity, time to progression, and overall survival. Forty-four patients were included and 40 were eligible. The mean age was 60.5 years (range 40.7–72.1), and 75% had stage IIIB disease. Six patients underwent complete R0 resection including 2 pathologic complete responses after a planned intermediate evaluation. Thirty-three patients completed CHRT. The objective response rate was 65% (95% CI 50.2–79.8). Grade 3–4 hematologic and digestive toxicities were observed mainly during the induction phase. Grade 3 esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7 months, the median progression-free survival was 28.3 months (95% CI 11.0–35.0) and the median survival rate was 31.4 months. Cisplatin-docetaxel induction followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a feasible protocol associated with a promising response rate and acceptable toxicity.
The Antioxidant Role of Paraoxonase 1 and Vitamin E in Three Autoimmune Diseases
Authors: Ramadan R. , Tawdy A. , Abdel Hay R. , Rashed L. , Tawfik D.
Published: September 2012

Purpose of the Study: To investigate the role of paraoxonase 1 (PON1) and vitamin E in the pathogenesis of some autoimmune diseases, and to correlate their levels with the disease activity. Procedures: This randomized case control study was performed on 60 subjects: 45 patients [suffering from psoriasis, vitiligo and alopecia areata (AA) 15 patients each group] and 15 healthy controls. Venous blood and tissue biopsy were collected from each subject to estimate the levels of vitamin E and PON1. Results: All patients showed significantly lower levels of both PON1 and vitamin E in tissue and serum than the controls (p < 0.001). Conclusion: An association between oxidative stress and pathogenesis of these autoimmune diseases is identified. Attenuation of oxidative stress might be a relevant therapeutic approach and it would be useful to recommend additional drugs with antioxidant effects in the treatment of these conditions.
The Impact of Chronic Obstructive Pulmonary Disease and Smoking on Mortality and Kidney Transplantation in End-Stage Kidney Disease
Authors: Kent Brian D. , Eltayeb Elhadi E. , Woodman Alastair , Mutwali Arif , Nguyen Hoang T. , Stack Austin G.
Published: September 2012

Background: Chronic obstructive pulmonary disease (COPD) and tobacco use are leading causes of morbidity and mortality. The prevalence and clinical impact of COPD on mortality and kidney transplantation among patients who begin dialysis therapy is unclear. Methods: We explored the clinical impact of COPD and continued tobacco use on overall mortality and kidney transplantation in a national cohort study of US dialysis patients. National data on all dialysis patients (n = 769,984), incident between May 1995 and December 2004 and followed until October 31, 2006, were analyzed from the United States Renal Data System. Prevalence and period trends were determined while multivariable Cox regression evaluated relative hazard ratios (RR) for death and kidney transplantation. Results: The prevalence of COPD was 7.5% overall and increased from 6.7 to 8.1% from 1995–2004. COPD correlated significantly with older age, cardiovascular conditions, cancer, malnutrition, poor functional status, and tobacco use. Adjusted mortality risks were significantly higher for patients with COPD (RR = 1.20, 95% CI 1.18–1.21), especially among current smokers (RR = 1.28, 95% CI 1.25–1.32), and varied inversely with advancing age. In contrast, the adjusted risks of kidney transplantation were significantly lower for patients with COPD (RR = 0.47, 95% CI 0.41–0.54, for smokers and RR = 0.54, 95% CI 0.50–0.58, for non-smokers) than without COPD [RR = 0.72, 95% CI 0.70–0.75, for smokers and RR = 1.00 for non-smokers (referent category)]. Conclusions: Patients with COPD who begin dialysis therapy in the US experience higher mortality and lower rates of kidney transplantation, outcomes that are far worse among current smokers.
Clinical Characteristics and Outcomes of Patients with Clinically Unsuspected Pulmonary Embolism versus Patients with Clinically Suspected Pulmonary Embolism
Authors: Shteinberg Michal , Segal-Trabelsy Miriam , Adir Yochai , Laor Arie , Vardi Moshe , Bitterman Haim
Published: September 2012

Background: The routine use of multidetector computed tomography has led to increased detection of unsuspected pulmonary embolism (UPE), with questionable benefit for diagnosis and treatment. Objective: The purpose of this work was to compare the clinical characteristics and prognosis of patients with UPE to patients with suspected PE (SPE). Methods: We retrospectively reviewed the charts of patients diagnosed with PE in a community-based university hospital between the years 2002 and 2007. UPE was defined as PE detected on CT scans performed for indications other than suspicion of PE. We compared patients with UPE to patients with SPE for differences in clinical features, electrocardiogram, imaging and echocardiographic findings. We also assessed the long-term outcomes using electronic patient records. Results: Of 500 patients with PE, 408 had SPE and 92 had UPE. Patients with UPE were similar to patients with SPE regarding age and sex distribution. Malignancy was more prevalent in UPE patients (39 vs. 23%, p < 0.0068). UPE patients had significantly less tachypnea (37 vs. 57%, p = 0.0005), dyspnea (47 vs. 87%, p < 0.0001), chest pain (19 vs. 42%, p < 0.0001) and hypoxemia (36 vs. 55%, p = 0.0011). Mortality was higher in UPE patients (70.3 vs. 53%, p = 0.0029). The hazard ratio after adjustment for confounders including age, sex and malignancy was 1.546 (95% CI: 1.139–2.099, p = 0.0052). Conclusions: We suggest that UPE is more prevalent in patients with a malignancy and is associated with higher mortality despite a less severe clinical presentation. UPE may be a marker of poor prognosis.
Francisella tularensis Alters Human Neutrophil Gene Expression: Insights into the Molecular Basis of Delayed Neutrophil Apoptosis
Authors: Schwartz Justin T. , Bandyopadhyay Sarmistha , Kobayashi Scott D. , McCracken Jenna , Whitney Adeline R. , DeLeo Frank R. , Allen Lee-Ann H.
Published: September 2012

We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil gene expression over a 24-hour time period relative to the uninfected controls. Of approximately 47,000 genes analyzed, 3,435 were significantly up- or downregulated by LVS, including 365 unique genes associated with apoptosis and cell survival. Specific targets in this category included genes asso-ciated with the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2, BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via the NFĸB pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and RELA, IL1B, CAST, CDK2,GADD45B, BCL3, BIRC3, CDK2, IL1A, PBEF1, IL6, CXCL1, CCL4 and VEGF). The microarray data were confirmed by qPCR and pathway analysis. Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection, whereas BAX mRNA and protein were progressively downregulated. These data strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to sustain the viability of F. tularensis--infected neutrophils.
A Randomized Controlled Trial of Brain-Activating Rehabilitation for Elderly Participants with Dementia in Residential Care Homes
Authors: Yamagami Tetsuya , Takayama Yoshifumi , Maki Yohko , Yamaguchi Haruyasu
Published: September 2012

Background/Aims: We aimed to prove the effectiveness of brain-activating rehabilitation for dementia, which consisted of 5 principles: pleasant atmosphere, communication, praising, social role, and supportive care. Methods: The design was a randomized controlled trial that was not blinded. Fifty-four elderly participants with dementia (mean age: 85.2 years) were selected. Intervention based on the 5 principles of brain-activating rehabilitation was conducted for 1 h, twice a week, for 12 weeks (24 sessions). The control group had no treatment. Outcome measures consisted of two observation scales, namely sum of boxes in clinical dementia rating (CDR-SB) and the multidimensional observation scale for elderly subjects (MOSES), and two cognitive tests: the Hasegawa dementia scale revised (HDS-R) and trail making test A. Results: Repeated measure ANCOVA showed a significant interaction for total score of CDR-SB (F = 7.190, p = 0.015) and MOSES (F = 4.525, p = 0.038). There were no significant changes in the two cognitive test scores. Conclusion: Intervention based on the principles of brain-activating rehabilitation was effective in maintaining and improving daily life functions in elderly participants with dementia in residential care homes.
Benefits and Environmental Determinants of Physical Activity in Children and Adolescents
Authors: Loprinzi Paul D. , Cardinal Bradley J. , Loprinzi Kristina L. , Lee Hyo
Published: September 2012

In this review, we identify the health benefits associated with physical activity (PA); address the physical activity and sedentary guidelines issued by public health scientists as well as children’s compliance to these guidelines; discuss the importance of motor skill acquisition during early childhood; and identify different settings that contribute to physical activity participation and strategies for improving PA in these settings. Results show that regular participation in PA during childhood has numerous immediate benefits, including positive changes in adiposity, skeletal health, psychological health, and cardiorespiratory fitness. Additionally, motor skill development during early childhood may have immediate health benefits as well as long-lasting effects in adulthood. Furthermore, the benefits of PA during childhood also appear to positively influence adult health outcomes, such as increased bone mineral density. Key environmental settings that have been shown to influence children’s PA behavior include child care, active commuting to and from school, school recess, school physical education, after-school programs, churches, medical settings, and the home environment. Recommendations for practitioners and researchers are discussed.
African Rainfall Climatology Version 2 for Famine Early Warning Systems
Authors: Novella Nicholas S. , Thiaw Wassila M.
Published: September 2012

This paper describes a new gridded, daily 29-yr precipitation estimation dataset centered over Africa at 0.1° spatial resolution. Called the African Rainfall Climatology, version 2 (ARC2), it is a revision of the first version of the ARC. Consistent with the operational Rainfall Estimation, version 2, algorithm (RFE2), ARC2 uses inputs from two sources: 1) 3-hourly geostationary infrared (IR) data centered over Africa from the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) and 2) quality-controlled Global Telecommunication System (GTS) gauge observations reporting 24-h rainfall accumulations over Africa. The main difference with ARC1 resides in the recalibration of all Meteosat First Generation (MFG) IR data (1983–2005). Results show that ARC2 is a major improvement over ARC1. It is consistent with other long-term datasets, such as the Global Precipitation Climatology Project (GPCP) and Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP), with correlation coefficients of 0.86 over a 27-yr period. However, a marginal summer dry bias that occurs over West and East Africa is examined. Daily validation with independent gauge data shows RMSEs of 11.3, 13.4, and 14, respectively, for ARC2, Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis 3B42, version 6 (3B42v6), and the CPC morphing technique (CMORPH) for the West African summer season. The ARC2 RMSE is slightly higher for Ethiopia than those of CMORPH and 3B42v6. Both daily and monthly validations suggested that ARC2 underestimations may be attributed to the unavailability of daily GTS gauge reports in real time, and deficiencies in the satellite estimate associated with precipitation processes over coastal and orographic areas. However, ARC2 is expected to provide users with real-time monitoring of the daily evolution of precipitation, which is instrumental in improved decision making in famine early warning systems.
GPS Precipitable Water as a Diagnostic of the North American Monsoon in California and Nevada
Authors: Means James D.
Published: September 2012

Precipitable water derived from archived global positioning system (GPS) zenith travel-time delays is used to describe the seasonal and interannual variation of the North American monsoon in California and Nevada. A 3-hourly dataset of precipitable water from 2003 to 2009, for over 500 sites in California and Nevada using temperature and pressure interpolated from the North American Regional Reanalysis (NARR), is constructed to study the temporal and spatial extent of the North American monsoon in the desert regions of California and Nevada. The statistical distribution of precipitable water values is shown to delineate the region that is most often affected by the monsoonal influence. A normalized precipitable water index is employed to indicate when the monsoon starts and stops and to investigate spatial variability. The GPS network provides much higher spatial resolution than other meteorological networks using surface-based methods, such as dewpoint criteria and rainfall, and is seen to contain comparable ability in capturing temporal variations. This dataset reveals the northwestward propagation of the monsoon onset both synoptically and seasonally. The GPS observations indicate that in the mean the decay of the monsoon is less well defined than the onset. Seven-year reanalysis 700-mb geopotential height composites for the monsoon onset and 3 days prior indicate that the onset of the monsoon is associated with a shift in the synoptic pattern characterized by upper-level high pressure building from the east and offshore troughing retreating to the northwest.
Transient Climate Response in a Two-Layer Energy-Balance Model. Part I: Analytical Solution and Parameter Calibration Using CMIP5 AOGCM Experiments
Authors: Geoffroy O. , Saint-Martin D. , Olivié D. J. L. , Voldoire A. , Bellon G. , Tytéca S.
Published: September 2012

This is the first part of a series of two articles analyzing the global thermal properties of atmosphere–ocean coupled general circulation models (AOGCMs) within the framework of a two-layer energy-balance model (EBM). In this part, the general analytical solution of the system is given and two idealized climate change scenarios, one with a step forcing and one with a linear forcing, are discussed. These solutions give a didactic description of the contributions from the equilibrium response and of the fast and slow transient responses during a climate transition. Based on these analytical solutions, a simple and physically based procedure to calibrate the two-layer model parameters using an AOGCM step-forcing experiment is introduced. Using this procedure, the global thermal properties of 16 AOGCMs participating in phase 5 of the Coupled Model Intercomparison Project (CMIP5) are determined. It is shown that, for a given AOGCM, the EBM tuned with only the abrupt 4×CO2 experiment is able to reproduce with a very good accuracy the temperature evolution in both a step-forcing and a linear-forcing experiment. The role of the upper-ocean and deep-ocean heat uptakes in the fast and slow responses is also discussed. One of the main weaknesses of the simple EBM discussed in this part is its ability to represent the evolution of the top-of-the-atmosphere radiative imbalance in the transient regime. This issue is addressed in Part II by taking into account the efficacy factor of deep-ocean heat uptake.
Atmospheric Forcing of the Winter Air–Sea Heat Fluxes over the Northern Red Sea
Authors: Papadopoulos Vassilis P. , Abualnaja Yasser , Josey Simon A. , Bower Amy , Raitsos Dionysios E. , Kontoyiannis Harilaos , Hoteit Ibrahim
Published: September 2012

The influence of the atmospheric circulation on the winter air–sea heat fluxes over the northern Red Sea is investigated during the period 1985–2011. The analysis based on daily heat flux values reveals that most of the net surface heat exchange variability depends on the behavior of the turbulent components of the surface flux (the sum of the latent and sensible heat). The large-scale composite sea level pressure (SLP) maps corresponding to turbulent flux minima and maxima show distinct atmospheric circulation patterns associated with each case. In general, extreme heat loss (with turbulent flux lower than −400 W m−2) over the northern Red Sea is observed when anticyclonic conditions prevail over an area extending from the Mediterranean Sea to eastern Asia along with a recession of the equatorial African lows system. Subcenters of high pressure associated with this pattern generate the required steep SLP gradient that enhances the wind magnitude and transfers cold and dry air masses from higher latitudes. Conversely, turbulent flux maxima (heat loss minimization with values from −100 to −50 W m−2) are associated with prevailing low pressures over the eastern Mediterranean and an extended equatorial African low that reaches the southern part of the Red Sea. In this case, a smooth SLP field over the northern Red Sea results in weak winds over the area that in turn reduce the surface heat loss. At the same time, southerlies blowing along the main axis of the Red Sea transfer warm and humid air northward, favoring heat flux maxima.
Spatial Interpolation for Real-Time Rainfall Field Estimation in Areas with Complex Topography
Authors: Rogelis M. C. , Werner M. G. F.
Published: September 2012

For many hydrological applications interpolation of point rainfall measurements is needed. One such application is flood early warning, particularly where spatially distributed hydrological models are used. Operation in real time poses challenges to the interpolation procedure, as this should then both be automatic and efficiently provide robust interpolation of gauged data. The differences in performance of ordinary kriging, universal kriging, and kriging with external drift with individual and pooled variograms were assessed for 139 daily datasets with significant precipitation in a study area in Bogotá, Colombia. Interpolators were compared using the percentage of variability explained and the root-mean-square error found in cross validation, aiming at identifying a procedure for real-time interpolation. The results showed that interpolators using pooled variograms provide a performance comparable to when the interpolators were applied to the storms individually, showing that they can be used successfully for interpolation in real-time operation in the study area. The analysis identified limitations in the use of kriging with external drift. Only when the adjusted R2 between the secondary variables and precipitation is higher than the percentage of variability explained found in ordinary kriging, then kriging with external drift provided a consistent improvement. This interpolator was found to give a lower performance in all other cases. The distribution of precipitation over basins of interest for each of the storms, derived through sampling rainfall fields generated through conditional Gaussian simulation, shows that, while differences between the interpolators may appear to be significant, the variability of the precipitation volume is less significant.
Coping with information obesity: A diet for information professionals
Authors: Brown Scott
Published: September 2012

The author looks at the concept of ‘information obesity’ – analogous to physical obesity – especially as it applies to information professionals. The author examines causes, such as information overload, and additional factors that make information professionals prone to information obesity. The article concludes with practical and philosophical suggestions for preventing and coping with information obesity, and an overview of ideas around the concept of ‘slow information’.
Gaining additional value from secondary data resources: Using existing internal data and knowledge to create new company-centric resources
Authors: Carter Denise
Published: September 2012

Information teams within biopharmaceutical organizations are usually the decision-makers on purchasing external data resources, matching customer and business requirements to the most useful and cost-effective resource. Many of these resources are provided for end-user access and the information teams also use them to answer regular and ad hoc enquiries and feed into regular operations such as issuing alerts, or creating monthly competitor overviews. In today’s increasingly cost-conscious environment it is important to seek ways to increase value from investments in information resources. Information teams also need to demonstrate the relevance of their skills and services to the organization they serve and show how they contribute to the organization’s aims in tangible ways. This article describes two instances of using data from externally subscribed resources, combined with internal explicit and tacit knowledge to create new company-centric resources: a global epidemiology resource and a market attractiveness platform for assessing commercial-viability for products in emerging markets.
The challenge of advancement
Authors: Edgar Sue
Published: September 2012

The challenges and pitfalls of advancement can often hamper information professionals from making a career move. In looking back since a previous article explored the potential demise of the corporate information unit, this article focuses on the changes in economic models, service management and how professionals should approach making a move. In interviews with four senior information professionals based in the UK and informal discussions with several senior professionals in New York, common themes were found. Making a move for the sake of it may not necessarily advance your career. But how can you be successful in taking that next step?
Misinformation and Its Correction
Authors: Lewandowsky Stephan , Ecker Ullrich K. H. , Seifert Colleen M. , Schwarz Norbert , Cook John
Published: September 2012

The widespread prevalence and persistence of misinformation in contemporary societies, such as the false belief that there is a link between childhood vaccinations and autism, is a matter of public concern. For example, the myths surrounding vaccinations, which prompted some parents to withhold immunization from their children, have led to a marked increase in vaccine-preventable disease, as well as unnecessary public expenditure on research and public-information campaigns aimed at rectifying the situation.

We first examine the mechanisms by which such misinformation is disseminated in society, both inadvertently and purposely. Misinformation can originate from rumors but also from works of fiction, governments and politicians, and vested interests. Moreover, changes in the media landscape, including the arrival of the Internet, have fundamentally influenced the ways in which information is communicated and misinformation is spread.

We next move to misinformation at the level of the individual, and review the cognitive factors that often render misinformation resistant to correction. We consider how people assess the truth of statements and what makes people believe certain things but not others. We look at people’s memory for misinformation and answer the questions of why retractions of misinformation are so ineffective in memory updating and why efforts to retract misinformation can even backfire and, ironically, increase misbelief. Though ideology and personal worldviews can be major obstacles for debiasing, there nonetheless are a number of effective techniques for reducing the impact of misinformation, and we pay special attention to these factors that aid in debiasing.

We conclude by providing specific recommendations for the debunking of misinformation. These recommendations pertain to the ways in which corrections should be designed, structured, and applied in order to maximize their impact. Grounded in cognitive psychological theory, these recommendations may help practitioners—including journalists, health professionals, educators, and science communicators—design effective misinformation retractions, educational tools, and public-information campaigns.
The Orthodox Church of Crete, 1645–1735: a case study of the relation between sultanic power and patriarchal will
Authors: Tellan Elif Bayraktar
Published: September 2012

The Ottoman policies towards the Orthodox patriarchate and its clergymen have been discussed in a number of articles. For some scholars the relationship is one of purely financial character, with the patriarch being a mere tax collector, whereas for others the patriarch is acting as ethnarch of his millet, as defined by supporters of the millet theory. In this case study, the re-establishment of the Orthodox Church on the island of Crete testifies to the complexity of the relationship between the patriarch and the sultan. The struggle of the metropolitans of Crete to establish their authority from 1651 to 1735 is connected to the history of the Greek Orthodox patriarchate in the Ottoman capital.
Stephanus the Philosopher and Ps. Elias: a case of mistaken identity
Authors: Roueché Mossman
Published: September 2012

The assumption, based on studies of the life and works of the late-sixth to seventh century philosopher, Stephanus, by Herman Usener and Wanda Wolska-Conus, that (1) the seventh century author of the commentary on De Interpretatione was summoned by the Emperor Heraclius from Alexandria to take up teaching post in Constantinople at a newly founded imperial institution of higher education (according to Usener) and (2) the same Stephanus was the Constantinopolitan author of the anonymous Prolegomena Philosophiae and Commentary on Porphyry’s Isagoge published by L.G. Westerink under the name of Ps. Elias (according to Wolska-Conus), is questioned and it is shown that Usener’s hypothesis of an imperial university under Heraclius was based on the anachronistic use of the titles oikoumenikos didaskalos and katholikos didaskalos to describe ‘Stephanus’ in some astrological and alchemical manuscripts. Accordingly, there is no evidence for an imperial institution of higher education under Heraclius. In addition, the evidence for Stephanus’ discussion of the term diairesis (as found in his commentary on De Interpretatione and the Dialogues ofSeverus bar Shakko) differs so completely from that ofPs. Elias that there can be no possibility that the two commentators are the same person. Accordingly, Wolska-Conus’ hypothesis of the identity of the two must be abandoned.
Measured residual stresses and integrity of pipeline girth welds
Authors: Law M , Luzin V
Published: September 2012

Pipeline girth welds were made by manual metal arc and semiautomatic flux cored arc welding processes, both without post-weld heat treatment. The residual stresses in these welds were measured by neutron diffraction on ANSTO's strain scanner, Kowari. The two welds had similar residual stress values and profiles. An integrity assessment of the welded branch connection was performed with a conservative estimate based on the measured values of residual stress, and values of residual stress predicted by BS 7910. The critical crack size based on the measurements was almost twice as large, showing the value of these measurements.
Contact mechanics: A review and some applications
Authors: Atkinson C. , Martínez-Esnaola J. M. , Elizalde M. R.
Published: September 2012

A review of indentation contact fracture is given ranging from that resulting from pressure and percussion flaking of flint by early man to that produced by various shaped indentors on glasses and ceramics. A recent application is described of controlled damage by nanoindentation on initially defect free silicon wafer samples.
Role of trehalose in heat and desiccation tolerance in the soil bacterium Rhizobium etli
Authors: Reina-Bueno Mercedes , Argandoña Montserrat , Nieto Joaquín J , Hidalgo-García Alba , Iglesias-Guerra Fernando , Delgado María J , Vargas Carmen
Published: September 2012

Background

The compatible solute trehalose is involved in the osmostress response of Rhizobium etli, the microsymbiont of Phaseolus vulgaris. In this work, we reconstructed trehalose metabolism in R. etli, and investigated its role in cellular adaptation and survival to heat and desiccation stress under free living conditions.

Results

Besides trehalose as major compatible solute, R. etli CE3 also accumulated glutamate and, if present in the medium, mannitol. Putative genes for trehalose synthesis (otsAB/treS/treZY), uptake (aglEFGK/thuEFGK) and degradation (thuAB/treC) were scattered among the chromosome and plasmids p42a, p42c, p42e, and p42f, and in some instances found redundant. Two copies of the otsA gene, encoding trehalose-6-P-synthase, were located in the chromosome (otsAch) and plasmid p42a (otsAa), and the latter seemed to be acquired by horizontal transfer. High temperature alone did not influence growth of R. etli, but a combination of high temperature and osmotic stress was more deleterious for growth than osmotic stress alone. Although high temperature induced some trehalose synthesis by R. etli, trehalose biosynthesis was mainly triggered by osmotic stress. However, an otsAch mutant, unable to synthesize trehalose in minimal medium, showed impaired growth at high temperature, suggesting that trehalose plays a role in thermoprotection of R. etli. Desiccation tolerance by R. etli wild type cells was dependent of high trehalose production by osmotic pre-conditioned cells. Cells of the mutant strain otsAch showed ca. 3-fold lower survival levels than the wild type strain after drying, and a null viability after 4 days storage.

Conclusions

Our findings suggest a beneficial effect of osmotic stress in R. etli tolerance to desiccation, and an important role of trehalose on the response of R. etli to high temperature and desiccation stress.