bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Mild to Moderate Renal Impairment on the Pharmacokinetics of the Nucleoside Analog Hepatitis C Virus Polymerase Inhibitor Mericitabine
Authors: Haznedar Joshua , Moreira Sebastian , Marbury Thomas , Robson Richard , Smith William , Kulkarni Rohit , Munson Marie L. , Thommes James A. , Lemenuel‐Diot Annabelle , Washington Carla , Smith Patrick , Chen Ya‐Chi
Published: December 2013

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Mericitabine is the prodrug of RO4995855, a selective inhibitor of the hepatitis C virus (HCV) NS5B polymerase. This study assessed the effect of renal impairment on RO4995855 pharmacokinetics. In this open‐label study, HCV‐negative volunteers (18–75 years) with normal renal function (NRF: creatinine clearance [CLCR] >80 mL/min, n = 10) or stable renal impairment (mild: CLCR 50–80 mL/min, n = 10; moderate: CLCR 30–49 mL/min, n = 10) received oral mericitabine 1000 mg twice daily (BID) (500 mg BID for moderate renal impairment) for 5 days. Primary outcome measures were renal clearance, maximum plasma concentration (Cmax), and area under the concentration‐time curve (0–12 h) (AUC0–12) for RO4995855. Renal clearance decreased as renal function decreased. Relative to subjects with NRF, the geometric mean ratios (GMR) for AUC0–12 and Cmax in mild renal impairment subjects were 1.45 (90% confidence interval [CI], 1.26–1.66) and 1.14 (1.02–1.28), respectively. For moderate renal impairment subjects, the dose‐normalized GMR for AUC0–12 and Cmax relative to NRF subjects were 2.51 (90% CI, 2.19–2.88) and 1.76 (1.56–1.97), respectively. Renal clearance of RO4995855 declined in subjects with mild/moderate renal impairment following mericitabine. Dose adjustment of mericitabine may be required in patients with moderate renal impairment.
Differential timing of antibody‐mediated phagocytosis and cell‐free killing of invasive African Salmonella allows immune evasion
Authors: Siggins Matthew K. , O'Shaughnessy Colette M. , Pravin John , Cunningham Adam F. , Henderson Ian R. , Drayson Mark T. , MacLennan Calman A.
Published: December 2013

Nontyphoidal Salmonellae commonly cause fatal bacteraemia in African children lacking anti‐Salmonella antibodies. These are facultative intracellular bacteria capable of cell‐free and intracellular survival within macrophages. To better understand the relationship between extracellular and intracellular infection in blood and general mechanisms of Ab‐related protection against Salmonella, we used human blood and sera to measure kinetics of Ab and complement deposition, serum‐mediated bactericidal killing and phagocytosis of invasive African Salmonella enterica serovar Typhimurium D23580. Binding of antibodies peaked by 30 s, but C3 deposition lagged behind, peaking after 2–4 min. C5b‐9 deposition was undetectable until between 2 and 6 min and peaked after 10 min, after which time an increase in serum‐mediated killing occurred. In contrast, intracellular, opsonized Salmonellae were readily detectable within 5 min. By 10 min, around half of monocytes and most neutrophils contained bacteria. The same kinetics of serum‐mediated killing and phagocytosis were observed with S. enterica Typhimurium laboratory strain SL1344, and the S. enterica Enteritidis African invasive isolate D24954 and laboratory strain PT4. The differential kinetics between cell‐free killing and phagocytosis of invasive nontyphoidal Salmonella allows these bacteria to escape the blood and establish intracellular infection before they are killed by the membrane attack complex.
An epigenetic profile of early T‐cell development from multipotent progenitors to committed T‐cell descendants
Authors: Vigano Maria Alessandra , Ivanek Robert , Balwierz Piotr , Berninger Philipp , van Nimwegen Erik , Karjalainen Klaus , Rolink Antonius
Published: December 2013

Cellular differentiation of the T‐cell branch of the immune system begins with the HSC, which undergoes a series of stages characterized by progressive restriction in multipotency and acquisition of specific lineage identity At the molecular level, the restriction of cell potential, commitment, and differentiation to a specific lineage is achieved through the coordinated control of gene expression and epigenetic mechanisms. Here, we analyzed and compared the gene expression profiles and the genome‐wide histone modification marks H3K4me3 (H3 lysine 4 trimethylation) and H3K27me3 (H3 lysine 27 trimethylation) in (i) in vitro propagated HSCs, (ii) in vitro generated and propagated pro‐T cells derived from these stem cells, and (iii) double‐positive thymocytes derived from these pro‐T cells after injection into Rag‐deficient mice. The combined analyses of the different datasets in this unique experimental system highlighted the importance of both transcriptional and epigenetic repression in shaping the early phases of T‐cell development.
SQSTM1/p62/A170 regulates the severity of Legionella pneumophila pneumonia by modulating inflammasome activity
Authors: Ohtsuka Shigeo , Ishii Yukio , Matsuyama Masashi , Ano Satoshi , Morishima Yuko , Yanagawa Toru , Warabi Eiji , Hizawa Nobuyuki
Published: December 2013

Sequestosome1/A170/p62 (SQSTM1) is a scaffold multifunctional protein involved in several cellular events, such as signal transduction, cell survival, cell death, and inflammation. SQSTM1 expression by macrophages is induced in response to environmental stresses; however, its role in macrophage‐mediated host responses to environmental stimuli, such as infectious pathogens, remains unclear. In this study, we investigated the role of SQSTM1 in host responses to Legionella pneumophila, an intra‐cellular pathogen that infects macrophages, in both an SQSTM1‐deficient (SQSTM1−/−) mouse model and macrophages from these mice. Compared with wild‐type (WT) macrophages, the production and secretion of the proinflammatory cytokine IL‐1β was significantly enhanced in SQSTM1−/− macrophages after infection with L. pneumophila. Inflammasome activity, indicated by the level of IL‐18 and caspase‐1 activity, was also elevated in SQSTM1−/− macrophages after infection with L. pneumophila. SQSTM1 may interact with nucleotide‐binding oligomerization domain‐like receptor family, caspase recruitment domain‐containing 4 and nucleotide‐binding oligomerization domain like receptor family, pyrin domain containing 3 proteins to inhibit their self‐dimerization. Acute pulmonary inflammation induced by L. pneumophila and silica was enhanced in SQSTM1−/− mice with an increase in IL‐1β levels in the bronchoalveolar lavage fluids. These findings suggest that SQSTM1 is a negative regulator of acute pulmonary inflammation, possibly by regulating inflammasome activity and subsequent proinflammatory cytokine production.
Functionally responsive self‐reactive B cells of low affinity express reduced levels of surface IgM
Authors: Kirchenbaum Greg A. , St. Clair James B. , Detanico Thiago , Aviszus Katja , Wysocki Lawrence J.
Published: December 2013

Somatic gene rearrangement generates a diverse repertoire of B cells, many which have receptors possessing a range of affinities for self‐Ag. Newly generated B cells express high and relatively uniform amounts of surface IgM (sIgM), while follicular (FO) B cells express sIgM at widely varying levels. It is plausible, therefore, that downmodulation of sIgM serves as a mechanism to maintain weakly self‐reactive B cells in a responsive state by decreasing their avidity for self‐Ag. We tested this hypothesis by performing comparative functional tests with FO IgMhi and IgMlo B cells from the unrestricted repertoire of WT C57BL/6 mice. We found that FO IgMlo B cells mobilized Ca2+ equivalently to IgMhi B cells when the same number of sIgM molecules was engaged. In agreement, FO IgMlo B cells were functionally competent to produce an antibody response following adoptive transfer. The FO IgMlo cell population had elevated levels of Nur77 transcript, and was enriched with nuclear‐reactive specificities. Hybridoma sampling revealed that these B‐cell receptors were of low affinity. Collectively, these results suggest that sIgM downmodulation by low‐affinity, self‐reactive B cells preserves their immunocompetence and circumvents classical peripheral tolerance mechanisms that would otherwise reduce diversity within the B cell compartment.
Development of a potential method based on microchip electrophoresis with fluorescence detection for the sensitive determination of intracellular thiols in RAW264.7 cells
Authors: Tu Feng‐Qin , Zhang Li‐Yun , Guo Xiao‐Feng , Wang Hong , Zhang Hua‐Shan
Published: December 2013

This paper, for the first time, reported the development of a simple, rapid, and reliable method for the separation and sensitive determination of four thiol compounds including homocysteine, cysteine, glutathione, and N‐acetylcysteine based on glass MCE with fluorescence detection using a highly reactive fluorogenic probe, 1,3,5,7‐tetramethyl‐8‐phenyl‐(2‐maleimide)‐difluoroboradiaza‐s‐indacene (TMPAB‐o‐M), as the labeling reagent. TMPAB‐o‐M reacted selectively with thiols to produce highly fluorescent derivatives and the highest derivatization efficiency was achieved within 6 min in physiological conditions. After the optimization of separation conditions, a baseline separation of the four thiol compounds was achieved with the detection limits ranging from 2 nM for glutathione to 4 nM for cysteine (S/N = 3) and RSDs (n = 5) in the range of 3.2–3.8%. The proposed method was significantly sensitive compared to those using electrochemical or even LIF detection in MCE‐based setup reported previously, and applied to the determination of intracellular thiols in macrophage RAW264.7 cells.
Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21
Authors: Hibaoui Youssef , Grad Iwona , Letourneau Audrey , Sailani M Reza , Dahoun Sophie , Santoni Federico A , Gimelli Stefania , Guipponi Michel , Pelte Marie Françoise , Béna Frédérique , Antonarakis Stylianos E , Feki Anis
Published: December 2013

Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD‐SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual‐specificity tyrosine‐(Y)‐phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects.
Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S.
Authors: Wong Robert J. , Cheung Ramsey , Ahmed Aijaz
Published: December 2013

Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients with HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the Model for Endstage Liver Disease (MELD) scoring system in 2002 (3.3%, n = 143 in 2000 versus 12.2%, n = 714 in 2005 versus 23.3%, n = 1336 in 2012). The proportion of hepatitis C virus (HCV)-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 versus 46.3% in 2007 versus 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold. Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More important, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S. (Hepatology 2014;59:2188–2195)
Naringin Mitigates Erythrocytes Aging Induced by Paclitaxel: An In Vitro Study
Authors: Harisa Gamaleldin I.
Published: December 2013

In this study, the protective role of naringin (NAR) against paclitaxel (PTX)‐induced erythrocytes aging has been investigated using human erythrocyte as an in vitro model. Erythrocytes were incubated with PTX in the presence and absence of NAR. Incubation of erythrocytes with PTX resulted in increased protein carbonyl content and malondialdehyde and hemolysis percentage compared with control. Furthermore, a significant increase in the ratios of glutathione peroxidase/glutathione reductase, superoxide dismutase/glutathione peroxidase, and superoxide dismutase/catalase in PTX‐treated cells was observed, compared with control cells. In contrast, reduced glutathione/oxidized glutathione ratio and glucose‐6‐phosphate dehydrogenase activity were decreased upon PTX treatment. The simultaneous incubation of erythrocytes with PTX and NAR restored these variables to values similar to those of control erythrocytes. These results suggest that NAR inhibited PTX‐induced aging by lessening the PTX‐induced oxidative stress.
Randomized, placebo‐controlled single‐ascending‐dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS‐986001, in healthy subjects
Authors: Urata Y. , Paintsil E. , Cheng Y.‐C. , Matsuda T. , Sevinsky H. , Hawthorne D. , Bertz R. , Hanna G.J. , Grasela D. , Hwang C.
Published: December 2013

The objectives of this study were to evaluate the safety, tolerability and pharmacokinetics (PK) of BMS‐986001 as a single oral dose in healthy male subjects. Sixty‐four healthy male subjects were randomized to receive a single dose of BMS‐986001 or placebo in this single‐blind, placebo‐controlled, sequential ascending‐dose study. There were eight treatment groups (10, 30, 100, 300, 600, and 900 mg fed; and 100 and 300 mg fasted) of eight subjects each (BMS‐986001 n = 6/placebo n = 2). BMS‐986001 was well tolerated, with no serious adverse events (AEs), deaths, or discontinuations due to AEs reported. AEs were experienced by 14.6% of subjects receiving BMS‐986001; however, these did not appear to be dose related and were not considered to be related to study drug. BMS‐986001 was rapidly absorbed and exhibited a linear dose–exposure relationship across the dose range studied. PK appeared similar whether administered with or without food. Administration of BMS‐986001 as a single dose was generally safe and well tolerated. A linear dose–exposure relationship was seen across all doses studied, with no apparent food effect. Further clinical development is warranted.
Predicting the severity of acute bronchiolitis in infants: Should we use a clinical score or a biomarker?
Authors: Amat Flore , Henquell Cécile , Verdan Matthieu , Roszyk Laurence , Mulliez Aurélien , Labbé André
Published: December 2013

Krebs von den Lungen 6 antigen (KL‐6) has been shown to be a useful biomarker of the severity of Respiratory syncytial virus bronchiolitis. To assess the correlation between the clinical severity of acute bronchiolitis, serum KL‐6, and the causative viruses, 222 infants with acute bronchiolitis presenting at the Pediatric Emergency Department of Estaing University Hospital, Clermont‐Ferrand, France, were prospectively enrolled from October 2011 to May 2012. Disease severity was assessed with a score calculated from oxygen saturation, respiratory rate, and respiratory effort. A nasopharyngeal aspirate was collected to screen for a panel of 20 respiratory viruses. Serum was assessed and compared with a control group of 38 bronchiolitis‐free infants. No significant difference in KL‐6 levels was found between the children with bronchiolitis (mean 231 IU/mL ± 106) and those without (230 IU/mL ± 102), or between children who were hospitalized or not, or between the types of virus. No correlation was found between serum KL‐6 levels and the disease severity score. The absence of Human Rhinovirus was a predictive factor for hospitalization (OR 3.4 [1.4–7.9]; P = 0.006). Older age and a higher oxygen saturation were protective factors (OR 0.65[0.55–0.77]; P < 0.0001 and OR 0.67 [0.54–0.85] P < 0.001, respectively). These results suggest that in infants presenting with bronchiolitis for the first time, clinical outcome depends more on the adaptive capacities of the host than on epithelial dysfunction intensity. Many of the features of bronchiolitis are affected by underlying disease and by treatment. J. Med. Virol. 86:1944–1952, 2014. © 2013 Wiley Periodicals, Inc.
Effect of the IL28B Rs12979860 C/T polymorphism on the incidence and features of active cytomegalovirus infection in allogeneic stem cell transplant patients
Authors: Bravo Dayana , Solano Carlos , Giménez Estela , Remigia María José , Corrales Isabel , Amat Paula , Navarro David
Published: December 2013

The current study was aimed at investigating whether the single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene, had any effect on the incidence rate and the features of active CMV infection in the Allogeneic stem cell transplantation setting. This was a retrospective observational study including 151 patients undergoing T cell‐replete Allo‐SCT. Donor and recipient IL28 SNP genotype was determined by allele‐specific real‐time PCR. The incidence rate of active CMV infection was not significantly associated with either the donor or the recipient IL28B SNP genotype. Nevertheless, a trend towards a lower incidence of active CMV infection was noted in the donor T/T population with respect to the donor C/T and C/C population. The duration of first episodes of CMV DNAemia was significantly shorter in patients carrying the donor T/T genotype with respect to their C/C or C/T counterparts (P = 0.038). Peak CMV DNAmeia levels tended to be lower in patients carrying the T/T genotype (donor or recipient) than in C/C or C/T patients, although statistical significance was not reached. In conclusion the data presented pointed to a protective effect of the T allele (recessive genetic model) against CMV infection in the Allo‐SCT setting. J. Med. Virol. 86:838–844, 2014. © 2013 Wiley Periodicals, Inc.
Coccolithophore carbonate during the last 450 ka in the NW Pacific Ocean (ODP site 1209B, Shatsky Rise)
Authors: BORDIGA MANUELA , COBIANCHI MIRIAM , LUPI CLAUDIA , PELOSI NICOLA , VENTI NICHOLAS L. , ZIVERI PATRIZIA
Published: December 2013

This study focuses on Pleistocene–Holocene sediments from the Shatsky Rise (Ocean Drilling Program Site 1209B, NW Pacific Ocean). We quantify the contribution of calcite made by coccoliths in oceanic sediments, investigating the role of calcareous nannoplankton during the last 450 ka. Coccolith carbonate constitutes 60–90% of bulk carbonate. Coccolith carbonate accumulation rates (CARs) and CaCO3 fine fraction confirm that coccolithophores are major contributors to the carbonate export and accumulation. Primary productivity shows highest values from marine isotope stage (MIS) 12 to 8. Thereafter, although coccolith calcite content remains high, other sediment components, such as as foraminifera and biogenic opal, seem to be favored, perhaps related to an increase in fertilization by eolian dust. Our results demonstrate the important role of coccolithophore production and sedimentation on the regulation of ocean carbonate chemistry on time scales >1000–100 000 years. On glacial–interglacial scales, coccolithophore productivity could have affected deep‐water saturation by buffering deep‐sea CO2 through increased carbonate dissolution episodes. Spectral and wavelet analyses are consistent with CARs primarily driven by glacial–interglacial variability and obliquity‐controlled changes. Coccolith‐based paleoceanographic reconstructions allow us to establish that during the last 450 ka the mid‐latitudes of the NW Pacific are controlled by the dynamics of the El Niño Southern Oscillation perturbations and Boreal Monsoon system.
Testing the sensitivity of the East Antarctic Ice Sheet to Southern Ocean dynamics: past changes and future implications
Authors: FOGWILL CHRISTOPHER J. , TURNEY CHRISTIAN S. M. , MEISSNER KATRIN J. , GOLLEDGE NICHOLAS R. , SPENCE PAUL , ROBERTS JASON L. , ENGLAND MATHEW H. , JONES RICHARD T. , CARTER LIONEL
Published: December 2013

The stability of Antarctic ice sheets and their potential contribution to sea level under projected future warming remains highly uncertain. The Last Interglacial (135 000–116 000 years ago) provides a potential analogue, with global temperatures 2 °C higher and rates of sea‐level rise >5.6 m ka−1, leading to sea levels 6.6–9.4 m higher than present. The source(s) of this sea‐level rise remain fiercely debated. Here we report a series of independent model simulations exploring the effects of migrating Southern Hemisphere Westerlies (SHWs) on Southern Ocean circulation and Antarctic ice‐sheet dynamics. We suggest that southerly shifts in winds may have significantly impacted the sub‐polar gyres, inducing pervasive warming (0.2–0.8 °C in the upper 1200 m) adjacent to sectors of the East Antarctic Ice Sheet (EAIS), which due to their geometries and connectivity to the Southern Ocean are highly sensitive to ocean forcing. We conclude that the EAIS potentially made a substantial, hitherto unsuspected, contribution to interglacial sea levels, and given 21st‐century projections in the Southern Annular Mode and associated SHW migration, we highlight how pervasive circum‐Antarctic warming may threaten EAIS stability.
E‐PASS comprehensive risk score is a good predictor of postsurgical mortality from comorbid disease in elderly gastric cancer patients
Authors: Ariake Kyohei , Ueno Tatsuya , Takahashi Michinaga , Goto Shinji , Sato Shun , Akada Masanori , Naito Hiroo
Published: December 2013

Background and Objectives

The long‐term prognosis of elderly gastric cancer patients is poor because of the cancer and unrelated comorbidities. We investigated the risk factors for mortality after gastrectomy to aid surgeons in deciding the correct operative procedure for elderly gastric cancer patients.

Methods

A total of 414 gastric cancer patients surgically treated between 2002 and 2012 were divided into two groups A (≥75 years) and B (<75 years). Data were collected retrospectively and analyzed using the Estimation of Physiological Ability and Surgical Stress (E‐PASS) scoring system as a predictor of postoperative complications.

Results

Overall survival (P < 0.001), disease‐specific survival (P = 0.029), and survival rate related to comorbid disease (P < 0.001) were significantly reduced in elderly patients compared with younger patients. Surgical treatment for Group A involved lesser extent of nodal resection (P < 0.001). Multivariate analysis revealed that a comprehensive risk score (CRS) ≥0.5 based on the E‐PASS score (P = 0.022) and severe postoperative complication (P = 0.002) were independent risk factors for mortality from comorbid disease.

Conclusions

Thus, E‐PASS‐based CRS was a good predictor of comorbidity‐related mortality. CRS may help surgeons select elderly patients with gastric cancer for surgical or other therapies. J. Surg. Oncol. 2014 109:586–592. © 2013 Wiley Periodicals, Inc.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case‐control study from a Chinese center
Authors: Huang Chao‐Qun , Feng Jue‐Ping , Yang Xiao‐Jun , Li Yan
Published: December 2013

Background

Advanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case‐control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC.

Methods

The 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles.

Results

For the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0‐1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7–12.4) versus 13.7 (95% CI 10.0–16.5) months (P = 0.02), the 1‐, 2‐, and 3‐year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0‐1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit.

Conclusion

CRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety. J. Surg. Oncol 2014; 109:730–739. © 2013 The Authors. Journal of Surgical Oncology. Published by Wiley Periodicals, Inc.
APPRAISING AND SELECTING STRATEGIES TO COMBAT AND MITIGATE DESERTIFICATION BASED ON STAKEHOLDER KNOWLEDGE AND GLOBAL BEST PRACTICES IN CAPE VERDE ARCHIPELAGO
Authors: De Pina Tavares Jacques , Ferreira António J. D. , Reis Eduardo A. , Baptista Isaurinda , Amoros Regla , Costa Lenira , Furtado Adriano M. , Coelho Celeste
Published: December 2013

Desertification is the most disturbing and detrimental cause of rural vulnerability in Cape Verde, affecting families' material and environmental resources. Combating desertification in Cape Verde is complex because it involves addressing a mixture of endogenous (manual agriculture, fuel wood and fodder extraction, land tenure and steep slopes) and exogenous drivers (high rainfall variability, climate change, prolonged drought or heavy rainfall). To address and mitigate the adverse effects of desertification, it is necessary to develop an approach that identifies and brings together all the key stakeholders affected by and acting on the desertification issue, including land users, policy makers, managers, researchers and rural development technicians. This paper presents a hybrid methodology based on global best practices, applied in Cape Verde. It combines experiences and skills of local stakeholders (farmers, local association of land users and local non‐governmental organizations) with scientific knowledge of external stakeholders such as technicians of the Ministry of Rural Development, environmental advisors of Municipalities and researchers. Integration takes place following a participatory process of appraising and selecting desertification control strategies. The paper presents the first results obtained from application of the hybrid methodology to Ribeira Seca, the largest watershed of Santiago Island. The approach was evaluated with local and external stakeholders. Both groups appreciated that they could voice their views and discuss ways to overcome barriers and also to take full advantage of the opportunities offered by jointly selected promising desertification mitigation options. Copyright © 2013 John Wiley & Sons, Ltd.
FORMAL INSTITUTIONS AND THEIR ROLE IN PROMOTING SUSTAINABLE LAND MANAGEMENT IN BOTETI, BOTSWANA
Authors: Mulale K. , Chanda R. , Perkins J. S. , Magole L. , Sebego R. J. , Atlhopheng J. R. , Mphinyane W. , Reed M. S.
Published: December 2013

The aim of this paper is to discuss the role of existing policies, programmes and legislation in promoting sustainable land management and livelihoods in mid‐central Botswana. The paper is based on data from the survey of relevant literature, analysis of policy and legal documents, field observations and a series of stakeholder workshops held in the villages of Mopipi, Mokobaxane and Rakops in Boteti Sub‐District between 2008 and 2009. The study's findings indicate that formal land use and rangeland management institutions have influenced the process of environmental change in the study area, mostly in a negative way. Institutional failure and support to the expansion of the livestock sector have promoted overstocking; arable production support has encouraged land clearance in a drought‐prone and windy area; whereas protectionist wildlife management has been in conflict with, rather than complementary to, traditional uses of the communal rangelands. The environmental outcomes of all this have been the shrinkage of the Boteti commons, overgrazing, deforestation and wind erosion. The study recommends adoption of a community‐based natural resource management strategy, which could simultaneously secure livelihoods and conserve the commons. Copyright © 2013 John Wiley & Sons, Ltd.
Deposit formation from lubricant degradation: a uniform layer deposition model
Authors: Kouame Sylvain‐Didier B. , Vander Wal Randall L. , Perez Joseph
Published: December 2013

Reported is a new model describing deposit formation and ageing along the so‐called universal mass deposition curve. The penn state micro‐oxidation (PSMO) apparatus produced model deposits at varied test durations in order to study the ageing mechanism of thin film deposits from mineral base oil. Along the ‘universal’ mass deposition curve, mass deposition rates were correlated to film chemistry. Formed by concerted oxidation‐polymerisation reactions, chemical group and elemental content analyses were performed by Fourier transformed infrared spectroscopy‐attenuated total reflectance and energy dispersive spectroscopy, respectively. The results showed that deposit formation initiates as a film — uniform in composition. After an induction period, the film growth accelerates then slows and eventually falls off, with a decrease in mass often observed. These stages reflect underlying physical and chemical changes as the deposit progresses from an initial polymeric, lacquer‐type deposit, towards a final dark, carbonaceous deposit, along the universal mass deposition curve. Carbonyl, hydroxyl and sp3 hybridised carbon were identified as the main functional groups found across all deposit types albeit at different levels. Correlative behaviour was observed between changes in functional group infrared intensities and O‐atom and C‐atom content. These trends are interpreted as reflecting concerted deoxygenation and dehydrogenation processes, throughout the deposit, over the course of ageing, thus providing a foundation for the uniform layer model. Copyright © 2013 John Wiley & Sons, Ltd.
Findings from a fleet test on the performance of two engine oil formulations in automotive CNG engines
Authors: Macián V. , Tormos B. , Olmeda P. , Gómez Y. A.
Published: December 2013

This work presents a comparative assessment of engine oil performance on field test using urban transport vehicles powered by compressed natural gas engines using two different mineral oil formulations approved by engine manufacturer. The first one is considered as a baseline reference, and the second one is a higher quality formulation in terms of base stock refining and additive content. Higher quality oil has shown a significant enhanced lubricant performance, leading to reach the oil drain interval defined by engine manufacturer on these engines without penalties in maintenance costs.

In order to assess oil performance, an oil analysis programme has been established for oil samples collected from vehicles operated under real service conditions in an urban transport fleet. Monitored parameters include oxidation, nitration, aminic anti‐oxidant additives depletion, anti‐wear additives depletion, total acid number, total basic number and remaining useful life number (as an estimation of anti‐oxidant additive depletion including aminic and zinc dialkyldithiophosphate).

Results obtained in more than 90 samples from 15 different vehicles have shown higher degradation rates for low quality lubricant oil formulation. This deviation can be explained taking into account factors related with lower anti‐oxidant additives content and lower thermal stability that can be mainly related with the base stock quality. This lower oil performance can be finally converted into higher vehicle maintenance cost and lower engine reliability. Copyright © 2013 John Wiley & Sons, Ltd.
The effect of topical anesthetic hydration on the depth of thermal injury from the plasma skin regeneration device
Authors: Sanderson Alicia R. , Wu Edward C. , Liaw Lih‐Huei L. , Garg Rohit , Gangnes Richard A.
Published: December 2013

Background and Objectives

The plasma skin regeneration (PSR) device delivers thermal energy to the skin by converting nitrogen gas to plasma. Prior to treatment, hydration of the skin is recommended as it is thought to limit the zone of thermal damage. However, there is limited data on optimal hydration time. This pilot study aims to determine the effect of topical anesthetic application time on the depth of thermal injury from a PSR device using histology.

Study Design/Materials and Methods

PSR (1.8 and 3.5 J) was performed after 0, 30, or 60 minutes of topical anesthetic application. Rhytidectomy was then performed and skin was fixed for histologic analysis. Four patients (two control and four treatment sites per patient) undergoing rhytidectomy were recruited for the study. Each patient served as his/her own control (no hydration). A scoring system for tissue injury was developed. Epidermal injury, the presence of vacuolization, blistering, damage to adnexal structures, and depth of dermal collagen changes were evaluated in over 1,400 high‐power microscopy fields.

Results

There was a significant difference in the average thermal injury score, depth of thermal damage, and epidermal injury when comparing controls to 30 minutes of hydration (P = 0.012, 0.012, 0.017, respectively). There was no statistical difference between controls and 60 minutes of hydration or between 30 and 60 minutes of hydration. Epidermal vacuolization at low energy and patchy distribution of thermal injury was also observed.

Conclusion

Topical hydration influences the amount of thermal damage when applied to skin for 30 minutes prior to treatment with the PSR device. There was a trend toward decreasing thermal damage at 60 minutes, and there was no difference between treatment for 30 or 60 minutes. The data suggest that application of topical anesthetic for a short period of time prior to treatment with the PSR device is cost‐effective, safe, and may be clinically beneficial. Lasers Surg. Med. 46:127–131, 2014. © 2013 Wiley Periodicals, Inc.
Influence of Screw Profile Employed During Melt Mixing on the Micro‐scale Dispersion of MWCNTs in Poly(propylene)
Authors: Mayoral Beatriz , Garrett Graham , McNally Tony
Published: December 2013

The relationship between MWCNT dispersion and agglomerate size with the screw profile employed during mixing of MWCNTs and a PP in a twin‐screw extruder is investigated. Five screw configurations are designed based on an initial concept of forward conveying and kneading block elements and varying a number of other elements. A screw profile having a toothed mixing element and one reverse conveying element (S3) after the mixing zone is most effective at breaking down MWCNT primary agglomerates. Addition of a second and third reverse conveying element increases the practical residence time but promotes MWCNT re‐agglomeration. A screw profile with just forward conveying and kneading block elements (S1) yields the most uniform MWCNT dispersion.
Graphene–Epoxy Flexible Transparent Capacitor Obtained By Graphene–Polymer Transfer and UV‐Induced Bonding
Authors: Sangermano Marco , Chiolerio Alessandro , Veronese Giulio Paolo , Ortolani Luca , Rizzoli Rita , Mancarella Fulvio , Morandi Vittorio
Published: December 2013

A new approach is reported for the preparation of a graphene–epoxy flexible transparent capacitor obtained by graphene–polymer transfer and UV‐induced bonding. SU8 resin is employed for realizing a well‐adherent, transparent, and flexible supporting layer. The achieved transparent graphene/SU8 membrane presents two distinct surfaces: one homogeneous conductive surface containing a graphene layer and one dielectric surface typical of the epoxy polymer. Two graphene/SU8 layers are bonded together by using an epoxy photocurable formulation based on epoxy resin. The obtained material showed a stable and clear capacitive behavior.

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Results of the citalopram to enhance cognition in Huntington disease trial
Authors: Beglinger Leigh J. , Adams William H. , Langbehn Douglas , Fiedorowicz Jess G. , Jorge Ricardo , Biglan Kevin , Caviness John , Olson Blair , Robinson Robert G. , Kieburtz Karl , Paulsen Jane S.
Published: December 2013

Background

The objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD).

Methods

The study was randomized, double‐blind, and placebo‐controlled. Thirty‐three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM‐D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20 weeks), with practice and placebo run‐ins. The primary outcome was change in executive functioning.

Results

The intent to treat analysis was controlled for practice effects, comparing visits 1 and 2 to visits 5 and 6 for citalopram versus placebo. There were no significant benefits on the executive function composite (treatment‐placebo mean difference −0.167; 95% confidence interval [CI], −0.361 to 0.028; P = .092). Citalopram participants showed improved clinician‐rated depression symptoms on the HAM‐D (t = −2.02; P = 0.05). There were no group differences on motor ratings, self‐reported executive functions, psychiatric symptoms, or functional status.

Conclusions

There was no evidence that short‐term treatment with citalopram improved executive functions in HD. Despite excluding patients with active depression, participants on citalopram showed improved mood, raising the possibility of efficacy for subsyndromal depression in HD. © 2013 International Parkinson and Movement Disorder Society
DNA methylation of the MAPT gene in Parkinson's disease cohorts and modulation by vitamin E In Vitro
Authors: Coupland Kirsten G. , Mellick George D. , Silburn Peter A. , Mather Karen , Armstrong Nicola J. , Sachdev Perminder S. , Brodaty Henry , Huang Yue , Halliday Glenda M. , Hallupp Marianne , Kim Woojin S. , Dobson‐Stone Carol , Kwok John B.J.
Published: December 2013

Parkinson's disease (PD) is a neurodegenerative disorder for which environmental factors influence disease risk and may act via an epigenetic mechanism. The microtubule‐associated protein tau (MAPT) is a susceptibility gene for idiopathic PD. Methylation levels were determined by pyrosequencing of bisulfite‐treated DNA in a leukocyte cohort (358 PD patients and 1084 controls) and in two brain cohorts (Brain1, comprising 69 cerebellum controls; and Brain2, comprising 3 brain regions from 28 PD patients and 12 controls). In vitro assays involved the transfection of methylated promoter‐luciferase constructs or treatment with an exogenous micronutrient. In normal leukocytes, the MAPT H1/H2 diplotype and sex were predictors of MAPT methylation. Haplotype‐specific pyrosequencing confirmed that the H1 haplotype had higher methylation than the H2 haplotype in normal leukocytes and brain tissues. MAPT methylation was negatively associated with MAPT expression in the Brain1 cohort and in transfected cells. Methylation levels differed between three normal brain regions (Brain2 cohort, putamen < cerebellum < anterior cingulate cortex). In PD samples, age at onset was positively associated with MAPT methylation in leukocytes. Moreover, there was hypermethylation in the cerebellum and hypomethylation in the putamen of PD patients compared with controls (Brain2 cohort). Finally, leukocyte methylation status was positively associated with blood vitamin E levels, and the effect was more significant in H2 haplotype carriers; this result was confirmed in cells that were exposed to 100 μM vitamin E. The significant effects of sex, diplotype, and brain region suggest that hypermethylation of the MAPT gene is neuroprotective by reducing MAPT expression. The effect of vitamin E on MAPT represents a possible gene‐environment interaction. © 2013 International Parkinson and Movement Disorder Society
Gait disorders in fatal familial insomnia
Authors: Cortelli Pietro , Fabbri Margherita , Calandra‐Buonaura Giovanna , Capellari Sabina , Tinuper Paolo , Parchi Piero , Lugaresi Elio
Published: December 2013

Background

Fatal familial insomnia (FFI) is a hereditary autosomal‐dominant prion disease linked to a mutation of the prion protein gene and characterized by sleep and autonomic abnormalities at onset followed by motor disturbances. We describe gait abnormalities in 13 FFI cases with different disease durations.

Methods

Clinical records and corresponding videos of 13 FFI cases were regularly monitored from disease onset to death.

Results

Gait disturbances appeared in all FFI subjects 5 ± 2 months after disease onset following a distinct progression for the 2 genetic FFI variants. Homozygous patients developed only a cautious gait with some difficulties in turning and in tandem gait; heterozygous patients showed a clear progressive worsening of equilibrium with latero/retropulsion ultimately preventing standing and walking unaided.

Conclusions

The severity and features of gait dysfunction in FFI are related to the duration of the disease, which in turn is a result of the genotype. The evolving gait dysfunction in the disease course may mirror the spread of neuronal degeneration from the thalamus to other brain areas involved in the control of gait or may be the functional effect of a disturbed neuronal network in which the thalamus is a crucial relay. © 2013 International Parkinson and Movement Disorder Society
Modeling of thin isotropic elastic plates with small piezoelectric inclusions and distributed electric circuits
Authors: Canon Éric , Lenczner Michel
Published: December 2013

This paper is the second part of a work devoted to the modelling of thin elastic plates with small, periodically distributed piezoelectric inclusions. We consider the equations of linear elasticity coupled with the electrostatic equation, with various kinds of electric boundary conditions. We derive the corresponding effective models when the thickness a of the plate and the characteristic dimension ϵ of the inclusions tend together to zero, in the two following situations: first, when a ≃ ϵ, and second, when a ∕ ϵ tends to zero. Copyright © 2013 John Wiley & Sons, Ltd.
Spectral analysis and stability of thermoelastic Bresse system with second sound and boundary viscoelastic damping
Authors: Han Zhong‐Jie , Xu Gen‐Qi
Published: December 2013

In this paper, we consider the energy decay rate of a thermoelastic Bresse system with variable coefficients. Assume that the thermo‐propagation in the system satisfies the Cattaneo's law, which can eliminate the paradox of infinite speed of thermal propagation in the assumption of the Fourier's law in the classical theory of thermoelasticity. Meanwhile, we also discuss the effect of a boundary viscoelastic damping on the stability of this system. By a detailed spectral analysis, we obtain the expressions of the spectrum and deduce some spectral properties of the system. Then based on the distribution of the spectrum, we prove that the energy of the system with a boundary viscoelastic damping decays exponentially. However, it no longer decays exponentially if there is no boundary damping. Copyright © 2013 John Wiley & Sons, Ltd.
Existence of multiple solutions for quasilinear elliptic equation with critical Sobolev–Hardy terms
Authors: Li Yuanxiao , Gao Wenjie
Published: December 2013

The main purpose of this paper is to establish the existence of multiple solutions for quasilinear elliptic equation with Robin boundary condition involving the critical Sobolev–Hardy exponents. It is shown, by means of variational methods, that under certain conditions, the existence of nontrivial solutions are obtained. Copyright © 2013 John Wiley & Sons, Ltd.
Infinitely many solutions for a Hardy–Sobolev equation involving critical growth
Authors: Peng Shuangjie , Wang Chunhua
Published: December 2013

In this paper, by an approximating argument, we obtain infinitely many solutions for the following Hardy–Sobolev equation with critical growth:
urn:x-wiley:1704214:media:mma3060:mma3060-math-0001 provided N > 6 + t, where and Ω is an open bounded domain in , which contains some points x0 = (0,z0). Copyright © 2013 John Wiley & Sons, Ltd.
A note on the exact synchronization by groups for a coupled system of wave equations
Authors: Li Tatsien , Rao Bopeng
Published: December 2013

By means of a non‐exact controllability result, we show the necessity of the conditions of compatibility for the exact synchronization by two groups for a coupled system of wave equations with Dirichlet boundary controls. Copyright © 2013 John Wiley & Sons, Ltd.
Optimal control for a sixth order nonlinear parabolic equation
Authors: Liu Changchun , Wang Zhao
Published: December 2013

In this paper, we consider the optimal control problem for a sixth order nonlinear parabolic equation, which arising in oil‐water‐surfactant mixtures. Based on Lions' theory, we prove the existence of optimal solution. The optimality system is also established. Copyright © 2013 John Wiley & Sons, Ltd.
Estimating 2‐cycle fixed points of henon map using backpropagation neural networks
Authors: Margaris Athanasios , Goulianas Konstantinos , Diamantaras Konstantinos , Papadimitriou Theophilos
Published: December 2013

The objective of this research is the presentation of a feed‐forward neural network capable of estimating the 2‐cycle fixed points of Henon map by solving their defining nonlinear algebraic system. The network uses the back propagation algorithm and solves the aforementioned system for a set of values of the parameters α and β of Henon map. Besides the estimation of the fixed points, the paper includes the study of the network convergence and its speed for many different initial conditions. Copyright © 2013 John Wiley & Sons, Ltd.