bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐tablet regimen is associated with reduced efavirenz withdrawal in antiretroviral naïve or switching for simplification HIV‐infected patients
Authors: Fabbiani M , Grima P , Prosperi M , Fanti I , Colafigli M , Zaccarelli M , D'Avino A , Mondì A , Borghetti A , Fantoni M , Cauda R , Di Giambenedetto S
Published: November 2012

Purpose of the study

Efavirenz (EFV) is still discussed for its high rate of interruption due to adverse event, in particular central nervous system side effects (CNS‐SE). Aim of the study was to define if better drug formulations up to single tablet regimen (STR), including (EFV) plus NRTI backbone (tenofovir‐emtricitabine), reduced the risk of interruption.

Methods

From the database of two reference centers, patients starting any cART regimen including EFV+2 NRTI or switching to EFV+2 NRTI for simplification after virological suppression were selected. Probability of interruption by virological failure, side effects, CNS‐SE and any cause were assessed with survival analysis and Cox proportional hazard model.

Summary of results

Overall, 533 patients, starting EFV‐containing regimen from May 1998 to March 2012, were included (51.2% naïve, 48.8% switched). Patients characteristics: males 70.7%, median age 39 years, injecting drug use (IDU) 11.2%, median nadir CD4 194/mmc, median CD4 at EFV start 305/mmc: 38.7% started BID regimen, 43.9% OD regimen and 17.4% STR. At survival analysis, the overall proportion of EFV interruption was 19.1% at 1 year and 33.0% at 3 years; interruption for virological failure were 2.8% and 7.4% and for toxicity 10.2% and 15.9%, respectively. CNS‐SE accounted for about half of interruptions for toxicity (5.7% and 8.0% at 1 and 3 years, respectively). Naïve patients had a higher risk of interruption as compared to switched patients: 37.7% vs. 28.0% at 3 years (p=0.06). While no significant difference was observed comparing OD vs. B ID regimens, starting with STR was associated with significant lower proportion of overall interruption at 3 years (17.1% vs. 36.6%, p<0.01). No virological failure was observed with STR up to 3 years (0.0% vs. 8.9%, p=0.05); no difference of interruption by overall toxicity and higher, though non‐significant, frequency of interruption by CNS‐SE (12.8% vs. 6.8%) were also observed. STR also accounted for lower proportion of interruption by patient wish, including low adherence (1.5% vs. 12.3%, p=0.01). At adjusted Cox model, STR (HR: 0.44; 95% CI: 0.26–0.77) and male gender (HR: 0.71; 95% CI: 0.53–0.97) were associated with lower risk of EFV interruption and IDU with higher risk (HR: 1.64; 95% CI: 1.11–2.42).

Conclusions

In our experience, EFV co‐formulated in STR was associated with lower virological failure and higher adherence, despite keeping CNS toxicity, thus reducing the risk of treatment interruption.
Are we conSTRucting the best treatment regimens for all patients with HIV infection?
Authors: Friday D , Evans‐Jones J , Steedman N
Published: November 2012

The British HIV Association (BHIVA) 2012 guidelines for the treatment of HIV recommend patients start combination antiretroviral therapy (ART) containing tenofovir and emtricitabine as the nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone. BHIVA third agent preferred choices comprise efavirenz, boosted atazanavir, boosted darunavir and raltegravir, and the guidelines further state that ‘fixed dose combinations (FDC) of drugs can increase adherence’ [1]. Atripla is currently the only available single‐tablet regimen (STR) for the treatment of HIV which contains a combination of BHIVA preferred first‐line antiretrovirals (tenofovir, emtricitabine and efavirenz). In addition, studies have shown that Atripla can improve adherence, treatment satisfaction and outcomes for patients infected with HIV [2]. A retrospective case note review was conducted for all HIV‐positive patients attending a UK HIV centre and receiving ART. The purpose was to ascertain the proportion of patients receiving BHIVA preferred ART in its simplest dosing format (in this case Atripla) and to investigate whether there were clinically or virologically appropriate reasons why patients not on Atripla were prescribed more complex drug regimens. The total number of patients receiving ART at the time of review was 142, of which 47 (33%) were currently taking Atripla. Of the remaining 95 patients, 30 (32%) had taken Atripla or some of its components in the past and been changed from this for valid clinical or virological reasons. In addition, there were a further 34 cases (36%) where Atripla had never been offered to the patient for appropriate reasons and documentation of 8 instances in which Atripla had been declined by the patient. There remained, however, 28 cases (29%) where there was no documentation of Atripla having been considered or offered, and no apparent contraindications to the STR or its components. This included 4 patients with an elevated cardiovascular risk, all of whom were taking an abacavir‐containing ART regimen at the time of review. Despite extensive professional guidance on preferred ART regimens and evidence to suggest that STR can increase adherence and patient satisfaction there remain patients in clinical care taking more complex drug regimens with no clear indication for this. We would encourage physicians to identify such patients and to discuss with them their treatment options in the light of advances in ART combination preparations.
Elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) has durable efficacy and differentiated safety compared to atazanavir boosted by ritonavir plus emtricitabine/tenofovir DF at week 96 in treatment‐naïve HIV‐1‐infected patients
Authors: Rockstroh J , DeJesus E , Henry K , Molina J , Gathe J , Wei X , Fordyce M , Rhee M , Szwarcberg J
Published: November 2012

Purpose of the study

The primary Week 48 analysis of this ongoing, randomized, double‐blind, double‐dummy, active‐controlled Phase 3 international trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment‐naïve patients demonstrated that Quad was non‐inferior to atazanavir boosted by ritonavir (ATV/r) + FTC/TDF with a differentiated safety profile. We report the Week 96 interim data.

Methods

Key eligibility criteria included HIV‐1 RNA≥5,000 c/mL and eGFR≥70 mL/min. Virologic success (HIV‐1 RNA <50 c/mL) at Week 96 was assessed per snapshot algorithm. Adverse events and laboratory data were collected prospectively. Bone mineral density (BMD) was assessed by DEXA scan in a subgroup of patients.

Results

708 patients (90% male, 74% white, 41% with HIV‐1 RNA >100,000 c/mL) were randomized and treated. At Week 48, Quad was non‐inferior to ATV/r+FTC/TDF (90% vs 87%, difference 3.0%, 95% CI −1.9% to 7.8%). High rates of virologic success were maintained at Week 96 (83% vs 82%, difference 1.1%, 95% CI −4.5% to 6.7%). Subgroup analysis revealed similar rates of virologic success in patients with baseline HIV‐1 RNA >100,000 c/mL (82% vs 80%). Mean CD4 cell increases (cells/mm3) were 256 vs 261 at Week 96. Emergent resistance was infrequent (2% vs<1%). Rates of study drug discontinuation due to adverse events (AEs) were low and comparable (4% vs 6%). Rates of study drug discontinuation due to renal reasons remained low and similar through Week 96 (3 [0.8%] vs 2 [0.6%]); since Week 48, 1 patient in each group discontinued study drug due to serum creatinine (Cr) increase without features of proximal renal tubulopathy. Median increases from baseline in serum Cr (µmol/L [mg/dL]) in Quad vs ATV/r+FTC/TDF at Week 96 (10.6 vs 7.1 [0.12 vs 0.08]) were similar to those at Week 48 (10.6 vs 7.1 [0.12 vs 0.08]). Quad continued to have smaller increases (mmol/L [mg/dL]) in triglycerides (0.06 vs 0.18 [5 vs 16], P=0.012); Quad had greater increases in total cholesterol (0.36 vs 0.21 [14 vs 8], P=0.046) at Week 96 only; changes in LDL and HDL cholesterol were similar. Quad had smaller mean decreases (%) in BMD (hip: −3.16 vs ‐4.19, P=0.069, spine: −1.96 vs −3.54, P=0.049).

Conclusions

At Week 96, Quad demonstrated high rates of virologic suppression with low rates of resistance and a differentiated safety and tolerability profile relative to ATV/r+FTC/TDF. These results support the durable efficacy and long‐term safety of Quad in HIV‐1 infected patients.
Enhancing mass and energy integration by external recycle in reactive distillation columns
Authors: Chen Haisheng , Huang Kejin , Liu Wei , Zhang Liang , Wang Shaofeng , Wang San‐Jang
Published: November 2012

The synthesis and design of reactive distillation columns separating reacting mixtures with the most unfavorable relative volatilities (i.e., the reactants are the heaviest and lightest components with the products being the intermediate ones) are described. The unfavorable thermodynamics poses great difficulties in combining the reaction operation and the separation operation involved and limits severely the potential of reactive distillation columns in the reduction of capital investment (CI) and operating cost. To remove the limitation, we propose two strategies for facilitating the synthesis and design of this kind of reactive distillation columns in this article. One is to arrange prudentially the reactive section so as to strengthen internal energy integration between the reaction operation and the separation operation involved; that is, while the reactive section should be placed at the bottom of the reactive distillation columns separating exothermic reactions, it should be at the top of the reactive distillation columns separating endothermic reactions. The other is to introduce an external recycle flow between the two ends of the reactive distillation columns to reinforce internal mass integration and internal energy integration between the reaction operation and the separation operation involved; that is, whereas the external recycle flow should be directed from the top to bottom of the reactive distillation columns separating exothermic reactions, it should be from the bottom to top of the reactive distillation columns separating endothermic reactions. Separation of four hypothetical ideal (i.e., two quaternary and two ternary systems, respectively) and two real nonideal (i.e., two quaternary systems) reacting mixtures is chosen to evaluate the proposed strategies. The results show that they can considerably lower energy requirement besides a further reduction in CI. © 2012 American Institute of Chemical Engineers AIChE J, 59: 2015–2032, 2013
An efficient reformulation of the multiechelon stochastic inventory system with uncertain demands
Authors: Nyberg Axel , Grossmann Ignacio E. , Westerlund Tapio
Published: November 2012

Significance

It is shown that by reformulating the three‐stage multiechelon inventory system with specific exact linearizations, larger problems can be solved directly with mixed‐integer linear programming (MILP) without decomposition. The new formulation is significantly smaller in the number of continuous variables and constraints. An MILP underestimation of the problem can be solved as part of a sequential piecewise approximation scheme to solve the problem within a desired optimality gap.
Long‐Term Population Survey of the Sulawesi Black Macaques (Macaca nigra) at Tangkoko Nature Reserve, North Sulawesi, Indonesia
Authors: KYES RANDALL C. , ISKANDAR ENTANG , ONIBALA JANE , PAPUTUNGAN UMAR , LAATUNG SYLVIA , HUETTMANN FALK
Published: November 2012

The Sulawesi black macaque (Macaca nigra) population at Tangkoko Nature Reserve in North Sulawesi, Indonesia has been the focus of periodic study for over 30 years. The population has shown considerable decline during much of that time. Here we present the results of a long‐term population survey of the TangkokoM. nigra, conducted over the past decade, to provide updated information and on‐going assessment of the population. Line‐transect sampling was conducted annually from 1999 to 2002 and 2005 to 2011 along the same transect during a 2‐ to 3‐week survey period. Although further decline in the population was observed at the outset of the survey, over the subsequent 12‐year period we have seen stability in the population parameters with evidence of modest increases in both group and population density. During the 1999–2002 survey periods, there was a mean group density of 3.6 groups/km2and a mean population density of 39.8 individuals/km2. During 2005–2011, mean group density increased to 3.8 groups/km2and mean population density was 51.4 individuals/km2. The 2011 survey data indicated an estimated group density of 4.3 groups/km2and a population density of 61.5 individuals/km2. Given that our transect was located in the core of the Tangkoko reserve, our density estimates should be limited to that area of the reserve. One explanation for the apparent stabilization of the population may be tied to the increasing and sustained number of training and research programs being conducted at the reserve. This collective effort by local and international groups may be helping to reduce illegal activity in the reserve (i.e., hunting and habitat destruction) and generate greater awareness of this critically endangered species. Without the continued vigilance afforded by the existing research and training programs and the support and involvement of the local people, theM. nigraat the Tangkoko Nature Reserve will likely face further decline. Am. J. Primatol. 75:88‐94, 2013. © 2012 Wiley Periodicals, Inc.
Evaluating implicit judgments from image search clickthrough data
Authors: Smith Gavin , Brien Chris , Ashman Helen
Published: November 2012

The interactions of users with search engines can be seen as implicit relevance feedback by the user on the results offered to them. In particular, the selection of results by users can be interpreted as a confirmation of the relevance of those results, and used to reorder or prioritize subsequent search results. This collection of search/result pairings is called clickthrough data, and many uses for it have been proposed. However, the reliability of clickthrough data has been challenged and it has been suggested that clickthrough data are not a completely accurate measure of relevance between search term and results. This paper reports on an experiment evaluating the reliability of clickthrough data as a measure of the mutual relevance of search term and result. The experiment comprised a user study involving over 67 participants and determines the reliability of image search clickthrough data, using factors identified in previous similar studies. A major difference in this work to previous work is that the source of clickthrough data comes from image searches, rather than the traditional text page searches. Image search clickthrough data were rarely examined in prior works but has differences that impact the accuracy of clickthrough data. These differences include a more complete representation of the results in image search, allowing users to scrutinize the results more closely before selecting them, as well as presenting the results in a less obviously ordered way. The experiment reported here demonstrates that image clickthrough data can be more reliable as a relevance feedback measure than has been the case with traditional text‐based search. There is also evidence that the precision of the search system influences the accuracy of click data when users make searches in an information‐seeking capacity.
High‐accuracy hierarchical parallel technique for hidden Markov model‐based 3D magnetic resonance image brain segmentation
Authors: El‐Moursy Ali A. , ElAzhary Hanan , Younis Akmal
Published: November 2012

Scientific applications represent a dominant sector of compute‐intensive applications. Using massively parallel processing systems increases the feasibility to automate such applications because of the cooperation among multiple processors to perform the designated task. This paper proposes a parallel hidden Markov model (HMM) algorithm for 3D magnetic resonance image brain segmentation using two approaches. In the first approach, a hierarchical/multilevel parallel technique is used to achieve high performance for the running algorithm. This approach can speed up the computation process up to 7.8× compared with a serial run. The second approach is orthogonal to the first and tries to help in obtaining a minimum error for 3D magnetic resonance image brain segmentation using multiple processes with different randomization paths for cooperative fast minimum error convergence. This approach achieves minimum error level for HMM training not achievable by the serial HMM training on a single node. Then both approaches are combined to achieve both high accuracy and high performance simultaneously. For 768 processing nodes of a Blue Gene system, the combined approach, which uses both methods cooperatively, can achieve high‐accuracy HMM parameters with 98% of the error level and 2.6× speedup compared with the pure accuracy‐oriented approach alone. Copyright © 2012 John Wiley & Sons, Ltd.
Bayesian inference in measurement error models for replicated data
Authors: de Castro Mário , Bolfarine Heleno , Galea M.
Published: November 2012

This paper deals with Bayesian inference in measurement error models with unknown error covariances. Our formulation covers heteroscedastic and homoscedastic models for replicated data. Both equation‐error and no‐equation‐error models are included in our proposal. Resorting to data augmentation, we present a simulation‐based framework using the Gibbs sampler. Model selection is also briefly discussed. Results from a simulation study are reported. We work out an illustrative example with a real data set on measurements of mineral element contents in pottery samples. Copyright © 2012 John Wiley & Sons, Ltd.
Estimating brood‐specific reproductive inhibition potency in aquatic toxicity testing
Authors: Zhang Jing , John Bailer A. , Oris James T.
Published: November 2012

Effluents may contain chemicals that impact the mortality, growth, or reproduction of organisms in aquatic systems. A common endpoint analyzed in reproduction toxicology is the total young produced by organisms exposed to toxicants. In the present study, we propose using two Bayesian hierarchical models to analyze the brood‐specific reproduction count responses in aquatic toxicology experiments jointly and to estimate the brood‐specific concentration associated with a specified level of reproductive inhibition. A simulation study showed that the proposed models outperformed an approach where brood‐specific responses were modeled separately. In particular, this method provided potency estimates with smaller bias/variation and better coverage probability. The application of the proposed models is illustrated with an experiment where the impact of Nitrofen was studied. Copyright © 2012 John Wiley & Sons, Ltd.
Modeling spatiotemporal trends in the productivity of North Pacific Salmon
Authors: Chkrebtii Oksana , Cao Jiguo
Published: November 2012

Fisheries management of North Pacific salmon stocks greatly relies on the understanding of changes in spawning and survival over time and across habitats. Underlying the yearly observed number of surviving salmon is a productivity parameter that cannot be directly measured and, moreover, is masked by short‐term changes in the observed population. We model the unobserved productivity of chum, sockeye, and two broodlines of pink salmon along the Pacific Coast of North America as a smoothly varying function of time and spatial location based on the Ricker spawner–recruit model of salmon reproduction. The candidate models belong to the class of Gaussian additive models and require the selection of smoothing parameters that control the trade‐off between fit to the data and smoothness of the estimated functions. We select the smoothing parameters by optimizing the pseudo Bayes information criterion, which incorporates prior knowledge about the degree of smoothness of the estimated functions and is well suited for detecting low‐frequency oscillations in the data, such as those due to long‐term climate effects. Comparing the candidate models based on fit and model parsimony via the Akaike information criterion, we find that the productivity components of time and spatial location may be related nonlinearly. We find evidence of an increase in productivity in the mid‐1970s for chum and sockeye populations and a north–south inverse relationship in productivity among sockeye and odd‐year pink salmon stocks. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of cellulase producing Bacillus sp. for effective degradation of leaf litter biomass
Authors: Akhtar Nadeem , Sharma Ashish , Deka Deepmoni , Jawed M. , Goyal Dinesh , Goyal Arun
Published: November 2012

Cellulose degrading Bacillus spp. (AS1, AS2, and AS3) were isolated from cow dung and identified phylogenetically by 16S ribosomal RNA (16S rRNA) sequence analysis. Bacillus sp. AS1 showed 99% homology with Bacillus megaterium whereas, Bacillus sp. AS2 and AS3 were similar to B. subtilis. The activity of extracellular carboxymethyl cellulase in presence of 1% carboxymethyl cellulose at 50°C was 0.04 U/mL for Bacillus sp. AS1 and 0.06 U/mL for Bacillus sp. AS2 at pH 7.0, whereas higher activity of 0.08 U/mL was observed for Bacillus sp. AS3 at pH 9.0. Crude cellulase from all the three Bacillus sp. were stable over a wide range of pH (5.0–9.0) and thermally stable up to 60°C. Carboxymethyl cellulase, filter paperase, and β‐glucosidase activity of Bacillus sp. AS3 was 0.07, 0.02, and 0.04 U/ml, respectively. Degradation of leaf litter biomass treated by Bacillus sp. AS3 showed 47% drop in carbon:nitrogen (C:N) ratio and x‐ray diffractograph revealed decline in crystalline structure. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 1195–1201, 2013
Comparison of the energy efficiency of dairy production farms using different housing systems
Authors: Uzal Selda
Published: November 2012

Energy use is an important consideration for developing more sustainable agricultural practices. Identifying animal production methods that maximize energy efficiency and minimize greenhouse gas emissions is vital. This study determined the energy use and the energy use efficiency (EUE) of two specialized dairy farms with different barn planning systems in Konya, Turkey. Total energy use included both the direct energy and indirect energy consumed during the production of farm inputs. This study investigated changes in energy use and EUE between Dairy Farm A, with a freestall dairy cattle housing system (ADF), and Dairy Farm B, with loose housing systems (BDF).

The results showed that animal feed accounted for a high percentage of total energy use and that electricity comprised the major portion of the direct energy used on both farms. The total energy use per hectare was lower for ADF compared with BDF. The energy productivity of the farms was set at 5.4 L milk per 100 MJ−1and 3.9 L milk per 100 MJ−1 for energy use on ADF and BDF, respectively. EUE was highly dependent on the energy inputs. For that reason, it is recommended that freestall dairy cattle barns be used for dairy cattle breeding and milk production. © 2012 American Institute of Chemical Engineers Environ Prog, 32: 1202–1208, 2013
No evidence of the genotoxic potential of gold, silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest
Authors: Nam Sun‐Hwa , Kim Shin Woong , An Youn‐Joo
Published: November 2012

ABSTACT

Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l–1 for Au NPs, 32.3 mg l–1 for Ag NPs and 100 mg l–1 for ZnO NPs and TiO2 NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO2 NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are classified as non‐genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest. Copyright © 2012 John Wiley & Sons, Ltd.
Chronic exposure to low concentrations of strontium 90 affects bone physiology but not the hematopoietic system in mice
Authors: Synhaeve Nicholas , Wade‐Gueye Ndéye Marième , Musilli Stefania , Stefani Johanna , Grandcolas Line , Gruel Gaëtan , Souidi Maâmar , Dublineau Isabelle , Bertho Jean‐Marc
Published: November 2012

The aim of this work was to delineate the effects of chronic ingestion of strontium 90 (90Sr) at low concentrations on the hematopoiesis and the bone physiology. A mouse model was used for that purpose. Parent animals ingested water containing 20 kBq l−1 of 90Sr two weeks before mating. Offspring were then continuously contaminated with 90Sr through placental transfer during fetal life, through lactation after birth and through drinking water after weaning. At various ages between birth and 20 weeks, animals were tested for hematopoietic parameters such as blood cell counts, colony forming cells in spleen and bone marrow and cytokine concentrations in the plasma. However, we did not find any modification in 90Sr ingesting animals as compared with control animals. By contrast, the analysis of bone physiology showed a modification of gene expression towards bone resorption. This was confirmed by an increase in C‐telopeptide of collagen in the plasma of 90Sr ingesting animals as compared with control animals. This modification in bone metabolism was not linked to a modification of the phosphocalcic homeostasis, as measured by calcium, phosphorus, vitamin D and parathyroid hormone in the blood. Overall these results suggest that the chronic ingestion of 90Sr at low concentration in the long term may induce modifications in bone metabolism but not in hematopoiesis. Copyright © 2012 John Wiley & Sons, Ltd.
Increased SCF/c‐kit by hypoxia promotes autophagy of human placental chorionic plate‐derived mesenchymal stem cells via regulating the phosphorylation of mTOR
Authors: Lee Youjin , Jung Jieun , Cho Kyung Jin , Lee Seoung‐Kwan , Park Jong‐Wan , Oh IL‐Hoan , Kim Gi Jin
Published: November 2012

Hypoxia triggers physiological and pathological cellular processes, including proliferation, differentiation, and death, in several cell types. Mesenchymal stem cells (MSCs) derived from various tissues have self‐renewal activity and can differentiate towards multiple lineages. Recently, it has been reported that hypoxic conditions tip the balance between survival and death by hypoxia‐induced autophagy, although the underlying mechanism is not clear. The objectives of this study are to compare the effect of hypoxia on the self‐renewal of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and placental chorionic plate‐derived mesenchymal stem cells (CP‐MSCs) and to investigate the regulatory mechanisms of self‐renewal in each MSC type during hypoxia. The expression of self‐renewal markers (e.g., Oct4, Nanog, Sox2) was assessed in both cell lines. PI3K and stem cell factor (SCF) expression gradually increased in CP‐MSCs but were markedly downregulated in BM‐MSCs by hypoxia. The phosphorylation of ERK and mTOR was augmented by hypoxia in CP‐MSCs compared to control. Also, the expression of LC3 II, a component of the autophagosome and the hoof‐shaped autophagosome was detected more rapidly in CP‐MSCs than in BM‐MSCs under hypoxia. Hypoxia induced the expression of SCF in CP‐MSCs and increased SCF/c‐kit pathway promotes the self‐renewal activities of CP‐MSCs via an autocrine/paracrine mechanism that balances cell survival and cell death events by autophagy. These activities occur to a greater extent in CP‐MSCs than in BM‐MSCs through regulating the phosphorylation of mTOR. These findings will provide useful guidelines for better understanding the function of SCF/c‐kit in the self‐renewal and autophagy‐regulated mechanisms that promote of MSC survival. J. Cell. Biochem. 114: 79–88, 2012. © 2012 Wiley Periodicals, Inc.
Thermal recovery from a fractured medium in local thermal non‐equilibrium
Authors: Gelet Rachel , Loret Benjamin , Khalili Nasser
Published: November 2012

Thermal recovery from a hot dry rock (HDR) reservoir viewed as a deformable fractured medium is investigated with a focus on the assumption of local thermal non‐equilibrium (LTNE).

Hydraulic diffusion, thermal diffusion, forced convection and deformation are considered in a two‐phase framework, the solid phase being made by impermeable solid blocks separated by saturated fractures. The finite element approximation of the constitutive and field equations is formulated and applied to obtain the response of a generic HDR reservoir to circulation tests. A change of time profile of the outlet fluid temperature is observed as the fracture spacing increases, switching from a single‐step pattern to a double‐step pattern, a feature which is viewed as characteristic of established LTNE. A dimensionless number is proposed to delineate between local thermal equilibrium (LTE) and non‐equilibrium. This number embodies local physical properties of the mixture, elements of the geometry of the reservoir and the production flow rate. All the above properties being fixed, the resulting fracture spacing threshold between LTNE and LTE is found to decrease with increasing porosity or fluid velocity. The thermally induced effective stress is tensile near the injection well, illustrating the thermal contraction of the rock, while the pressure contribution of the fracture fluid is negligible during the late period. Copyright © 2012 John Wiley & Sons, Ltd.
Challenging Classic Project Management: Turning Project Uncertainties into Business Opportunities
Authors: Lechler Thomas G. , Edington Barbara H. , Gao Ting
Published: November 2012

The management of uncertainty during a project's implementation is not well understood. In general, uncertainties are treated similar to project risks by practitioners and by scholars as negative events threatening a project's implementation. Following the arguments of economists, uncertainties are a necessary condition for the existence of opportunities. This research aims to identify specific classes of opportunities and specific contextual situations under which they occur during the implementation of projects. An exploratory case study of 20 projects was conducted. Different categories of opportunities and uncertainties were identified. All identified opportunities were connected with at least one situation of uncertainty but not every situation of uncertainty relates to opportunities. The cases unveiled that risks are misperceived as uncertainties and some situations of project improvements were misperceived as opportunities. Our study sheds light on the limitations of classic project management and suggests that future project management education needs to include a deeper exposure to business context to better equip project managers for the challenge and opportunity posed by uncertainty during project implementation.
Ulipristal acetate: new oral treatment for uterine fibroids
Authors: McVeigh Enda
Published: November 2012

Ulipristal acetate is the first progesterone receptor modulator licensed for the preoperative treatment of uterine fibroids. Our New products review presents the clinical data relating to its efficacy and adverse events and considers its place in medical management of uterine fibroids.
GP guide to drugs used in palliative care: psychostimulants
Authors: Howard Rachel , Howard Paul
Published: November 2012

This is the third in a short series of articles that focus on what GPs should consider when monitoring and prescribing specialist‐initiated palliative‐care drugs. Here, the authors summarise the key issues around the shortterm use of psychostimulants in palliative care.
Kinetic energy spectra characteristics of two convection‐permitting limited‐area models AROME and Meso‐NH
Authors: Ricard D. , Lac C. , Riette S. , Legrand R. , Mary A.
Published: November 2012

Kinetic energy (KE) spectra are applied to evaluate two convection‐permitting models: the AROME numerical weather prediction operational model and the Meso‐NH research model, that share the same physics and differ only in the dynamics (semi‐Lagrangian semi‐implicit versus Eulerian explicit schemes).

A first analysis of AROME spectra for winter and summer seasons shows that the model‐derived spectra match the observational spectra well, including the transition between k−3 and k−5/3 regimes. The vertical distribution of the spectra is coherent with previous observational and numerical studies and the diurnal cycle has a strong impact on the amount of KE in the mesoscale during summer.

A comparative analysis of KE spectra for both models is then performed on a real case of individual convective cells that developed over plains, during the afternoon of 11 April 2007, characterized by a strong cold air outflow in the low levels.

AROME spectra are characterized by a coarser effective resolution than Meso‐NH, even without explicit diffusion, revealing the impact of the implicit diffusion of the semi‐implicit semi‐Lagrangian scheme used in AROME. For large time steps, the damping increases and can be attributed preferentially to the SI part of the SISL (semi‐implicit semi‐Lagrangian) formulation. Adiabatic runs show that the transition to a shallow mesoscale regime is still apparent even if the mesoscale KE variance strongly depends on the presence of the physical processes.

Effective resolution of Meso‐NH remains around 4–6Δx for horizontal grid spacings between 2.5 km and 250 m. The effects of subgrid mixing schemes are also investigated with Meso‐NH at 500 m horizontal grid spacing in the grey zone for turbulence, illustrating the difficulty in finding a good equilibrium between resolved and subgrid mixing at this scale.
Effects of the cold tongue in the South China Sea on the monsoon, diurnal cycle and rainfall in the Maritime Continent
Authors: Koseki Shunya , Koh Tieh‐Yong , Teo Chee‐Kiat
Published: November 2012

We investigate the effects of the cold tongue in the South China Sea (SCS) on the winter monsoon, rainfall and diurnal cycle in the maritime continent using a numerical model verified with satellite rainfall and reanalysis data. Composite analysis of the observation and reanalysis data based on cold tongue index indicates that the penetration of the monsoon to Java Sea is enhanced when the cold tongue is strong. A sensitivity experiment without the cold tongue shows that the winter monsoon is diminished over SCS and around coastal regions because of anomalous low‐level cyclonic circulation associated with enhanced convection over SCS due to the warmer sea surface temperature (SST). The diurnal cycle, in particular the night–morning rainfall, over the sea in coastal regions is modified. The effect on daytime rainfall over the land is relatively weaker. Along the northern coast of Java far from the SCS, the night–morning rainfall is much reduced over the Java Sea when the cold tongue is suppressed because of the weakened land‐breeze front as a result of the weakened northerly monsoon. In contrast, the afternoon–evening rainfall on Java Island is slightly enhanced, showing that the local impacts are not simply the result of large‐scale subsidence from the convective anomaly in the SCS. Along the northwestern coast of Borneo adjacent to the SCS, the weakened winter monsoon tends to reduce the rainfall at the land‐breeze front near the coastline. On the other hand, the warmer SST forces a stronger land breeze and the weakened monsoon encourages further and faster offshore propagation of the land‐breeze front. Consequently, the rainfall peak shifts further offshore in the sensitivity experiment. We conclude that the cold tongue has two effects, the sustenance of a strong monsoon (indirect effect) and the cooling of local SST (direct effect), which have opposite influences on the diurnal cycle in the Maritime Continent.
Understanding advances in the simulation of intraseasonal variability in the ECMWF model. Part II: The application of process‐based diagnostics
Authors: Hirons L. C. , Inness P. , Vitart F. , Bechtold P.
Published: November 2012

In Part I of this study it was shown that moving from a moisture‐convergent‐ to a relative‐humidity‐dependent organized entrainment rate in the formulation for deep convection was responsible for significant advances in the simulation of the Madden–Julian Oscillation (MJO) in the ECMWF model. However, the application of traditional MJO diagnostics were not adequate to understand why changing the control on convection had such a pronounced impact on the representation of the MJO.

In this study a set of process‐based diagnostics are applied to the hindcast experiments described in Part I to identify the physical mechanisms responsible for the advances in MJO simulation. Increasing the sensitivity of the deep convection scheme to environmental moisture is shown to modify the relationship between precipitation and moisture in the model. Through dry‐air entrainment, convective plumes ascending in low‐humidity environments terminate lower in the atmosphere. As a result, there is an increase in the occurrence of cumulus congestus, which acts to moisten the mid troposphere. Due to the modified precipitation–moisture relationship more moisture is able to build up, which effectively preconditions the tropical atmosphere for the transition to deep convection. Results from this study suggest that a tropospheric moisture control on convection is key to simulating the interaction between the convective heating and the large‐scale wave forcing associated with the MJO.
Improved delay‐dependent stabilization of time‐delay systems with actuator saturation
Authors: Dey Rajeeb , Ghosh Sandip , Ray Goshaidas , Rakshit Anjan
Published: November 2012

This paper addresses the controller synthesis problem of linear time‐delay systems subjected to saturating control. Delay‐dependent regional stabilization criteria are derived based on Lyapunov–Krasovskii approach by using both the polytopic or dead‐zone representation of the saturation function. The main contribution of the paper lies in developing less conservative convex criterion in terms of LMIs to obtain superior results. On the basis of the derived stabilization criterion, an optimization problem is defined to compute the stabilizing state feedback gains with an aim to maximize the stabilizing region while guaranteeing the asymptotic stability of the closed‐loop system. Considering three numerical examples, an assessment of the polytopic and dead‐zone nonlinearity approaches is made. Copyright © 2012 John Wiley & Sons, Ltd.
Polysorbate20 adsorption layers below and above the critical micelle concentration over aluminum; cloud point and inhibitory role investigations at the solid/liquid interface
Authors: Fares Mohammad M. , Maayta A. K. , Al‐Qudah Mohammad A.
Published: November 2012

Non‐ionic polysorbate20 surfactant was used to produce adsorption protective layers below and above its critical micelle concentration (CMC) at the liquid/solid interface. The well‐ordered accumulation of surfactant molecules on the metal surface below the CMC led to the formation of oriented surfactant monolayers. On the other hand, as the surfactant concentration increased above the CMC, the monodisperse micelles, free surfactant molecules and oriented surfactant monolayers undergo aggregate formation and produce a turbid solution. The gradual increase in the number and size of aggregates leads to phase separation and hence disassembled protective layers that allow easier penetration of corrosive HCl at a metal surface. This was demonstrated by inhibition efficiency, activation energy, enthalpy and entropy of activation values. Two‐dimensional irregular crystalline sheets accumulated at the surface of aluminum, as shown by scanning electron micrographs. Adsorption of polysorbate20 at the aluminum surface exhibited a Temkin isotherm fit. Larger desorption processes at the cloud point demonstrate aggregate formation and phase separation, and hence poorer adsorption layers at the metal surface. Copyright © 2012 John Wiley & Sons, Ltd.
Does H → γγ taste like vanilla new physics?
Authors: Almeida L. G. , Bertuzzo E. , Machado P. A. N. , Funchal R. Zukanovich
Published: November 2012

Abstract

We analyse the interplay between the Higgs to diphoton rate and electroweak precision measurements constraints in extensions of the Standard Model with new uncolored charged fermions that do not mix with the ordinary ones. We also compute the pair production cross sections for the lightest fermion and compare them with current bounds.
Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in combination with docetaxel in advanced solid tumors
Authors: Awada A. H. , Dumez H. , Hendlisz A. , Wolter P. , Besse-Hammer T. , Uttenreuther-Fischer M. , Stopfer P. , Fleischer F. , Piccart M. , Schöffski P.
Published: November 2012

Background A phase I study to assess the maximum tolerated dose (MTD) of a short course of afatinib in combination with docetaxel for the treatment of solid tumors. Methods Patients with advanced solid malignancies received docetaxel 75 mg/m2 intravenously on day 1 and oral afatinib once daily on days 2–4, in 3-week treatment cycles. The afatinib dose was escalated in successive cohorts of 3–6 patients until dose-limiting toxicity (DLT). The MTD cohort was expanded to 13 patients. Pharmacokinetic parameters were assessed. Results Forty patients were treated. Afatinib doses were escalated to 160 mg/day in combination with 75 mg/m2 docetaxel. Three patients had drug-related DLTs during cycle 1. The MTD was defined as 90 mg/day afatinib (days 2–4) with docetaxel 75 mg/m2. The most frequent drug-related adverse events (all grades) were alopecia, diarrhea, stomatitis (all 50 %) and rash (40 %, all grade ≤2). Three patients had confirmed responses, two patients had unconfirmed responses and nine patients had durable stable disease >6 cycles. No pharmacokinetic interaction was observed. Conclusion Afatinib 90 mg administered for 3 days after docetaxel 75 mg/m2 is the MTD for this treatment schedule and the recommended phase II/phase III dose. This combination showed anti-tumor activity in phase I, with a manageable adverse-event profile.
Distribution and abundance of foliage‐arthropods across elevational gradients in the east and west Himalayas
Authors: Ghosh‐Harihar Mousumi
Published: November 2012

Elevational gradients are ideal for studying geographic variation in the distribution and abundance of organisms corresponding to predictable variation in climatic factors. This study provides a broad‐scale assessment of variation in distribution patterns of foliage‐dwelling arthropod orders along elevational gradients located across an extensive precipitation gradient in the Himalayas. Relative abundances of foliage‐dwelling arthropods were estimated from 16 sites during the summer months. Abundances declined significantly from east to west and peaked at intermediate elevations along elevational gradients, corresponding with trends in climatic variables.
Microtitration of Free Fatty Acids in Oil and Biodiesel Samples Using Absorbance and/or Fluorescence of Pyranine
Authors: Fedosov Sergey N. , Brask Jesper , Xu Xuebing
Published: November 2012

Free fatty acids (FFA) are measured before alkaline transesterification of oil and when testing quality of the produced biodiesel. Titration of FFA is usually monitored on a potentiometer (EN 14104 and ASTM D 664 methods) or employing the indicator phenolphthalein (AOCS Cd 3d‐63). Both procedures have some disadvantages including relatively large sample masses (2–20 g), elaborate maintenance of the electrode, subjective observation of the color transition, etc. Here we describe a microtitration method based on absorbance/fluorescence of pyranine (aqueous pK 7.3). All reactants were dissolved in a medium with universal solubility, which allowed accurate optical measurements. FFA standards and test samples (5–150 mg) were titrated on standard equipment, and the sigmoid titration curves were produced. The upper bend of each sigmoid corresponded to neutralization of FFA. Fluorescence of pyranine had better “signal to noise” characteristics than absorbance when working with heavily pigmented oil samples. Blind examination of different experimental mixtures (FFA = 0.15–40 %) revealed a close correspondence between the pyranine method and two other established procedures (EN 14104 and a variant of AOCS Cd 3d‐63).
Film‐Forming Properties of Blends of High‐Oleic Sunflower Oil with Polyalkyl Glycol
Authors: Bantchev Grigor B. , Biresaw Girma
Published: November 2012

The viscosity, density, and elastohydrodynamic film thicknesses of oil‐soluble polyalkyl glycols (PAG), high oleic sunflower oil (HOSuO), and their 50/50 (wt.%) blends were investigated. The viscosity and density of the blends were found to be predictable from the corresponding neat oil properties using simple mixing rules. Pressure–viscosity coefficients (PVC) of HOSuO, the two PAGs, and the two 50 wt% HOSuO/50 wt% PAG blends were calculated from measured film thickness data using the Hamrock‐Dowson method and compared to values estimated from literature data. Literature pressure‐density and viscosity‐temperature data for oils with high‐oleic acid group content were analyzed using the Tait and Casalini et al. models. Viscosity versus pressure data obtained from these analyses was used to calculate PVC using the Barus and Bair et al. models. The PVC values calculated from the literature data following this procedure showed reasonable agreement with that from film thickness data from this work.
Solid Fat Content as a Substitute for Total Polar Compound Analysis in Edible Oils
Authors: Bakota Erica L. , Winkler‐Moser Jill K. , Palmquist Debra E.
Published: November 2012

The solid fat contents (SFC) of heated edible oil samples were measured and found to correlate positively with total polar compounds (TPC) and inversely with triglyceride concentration. Traditional methods for determination of TPC require a laboratory setting and are time and solvent intensive. Therefore, SFC analysis represents a viable user‐friendly alternative to measuring total polar components in environments where low‐resolution NMR may already be in use, for example, in quality assurance environments. The slope of SFC measurements versus time was also found to correlate with the oxidative stability index of the edible oils studied.
Trigonella foenum‐graecum L. Seed Oil Obtained by Supercritical CO2 Extraction
Authors: Yang Renming , Wang Honglun , Jing Nianhua , Ding Chenxu , Suo Yourui , You Jinmao
Published: November 2012

Supercritical CO2 extraction (SC‐CO2) of fenugreek (Trigonella foenum‐graecum L.) seed oil and its chemical composition and antioxidant activity were investigated. A central composite design combined with response surface methodology was used to study extraction conditions including pressure, temperature, and time. The optimum extraction conditions were 28.5 MPa extraction pressure, 41 °C extraction temperature, and 118 min extraction time, where 3.78 % yield was predicted. Fenugreek seed oil extracted under optimum conditions by SC‐CO2 was mainly composed of 28.3 % C18:3, 33.45 % C18:2, 9.89 % C16, 8.1 % C18:1, 3.7 % C18, 0.71 % C20, and 0.61 % C22. The fenugreek oil was rich in unsaturated fatty acids (nearly 70 % of the total fatty acids), and polyunsaturated fatty acids accounted for 61.42 % (mass percentage) of the total amount. The 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging activity increased from 12.5 to 88.4 % when the concentration was increased from 1 to 12 mg/ml. The reducing power of the seed oil was concentration‐dependent. The antioxidant activity of the supercritical fluid extraction extract was superior to those obtained by Soxhlet extraction.