bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactivity of di‐iodine toward thiol: Desulfuration reaction of 5‐nitro‐2‐mercapto‐benzimidazole upon reaction with di‐iodine
Authors: Corban G. J. , Antoniadis C. D. , Hadjikakou S. K. , Kourkoumelis N. , Tyurin V. Yu. , Dolgano A. , Milaeva E. R. , Kubicki M. , Bernhardt P. V. , Tiekink E. R. T. , Skoulika S. , Hadjiliadis N.
Published: August 2012

The reaction of 2‐mercapto‐benzoic acid (H2MBA), 2‐mercato‐nicotinic acid (H2MNA), and 2‐mercapto‐pyrimidine (PMTH) with a twofold molar amount of di‐iodine (I2) results in the isolation of crystals of the neutral disulfides of formulae: {(HMBA)2·1/2(CH3CN)} (1), {(HMNA)2·(H2O)} (2), and (PMT)2 (3), respectively, when dichloromethane/acetonitrile/methanol (1) or dichloromethane (2,3) were used as solvents. The reaction of di‐iodine with thethiol PMTH and 2‐mercapto‐benzothiazole (MBZTH) yields the disulfide (PMT)2 (3), and the di‐iodine adduct of formula {[MBZTH‐I2]·[MBZTH]2} (4), respectively. The reaction of di‐iodine with 5‐nitro‐2‐mercapto‐benzimidazole (O2N‐MBZIMH) (5) in the presence of ferric trichloride hydrate (FeCl3·6H2O), in a 6:3:1 (I2:thiol:FeCl3·6H2O) molar ratio, results in cocrystal (6), which contain the desulfurated hydroxyl derivative O2N‐BZIMOH (6a) and unreacted O2N‐MBZIMH (6b) in a 3:1 molar ratio. The compounds were characterized by elemental analysis, FT‐IR, and 1H NMR spectroscopy. The crystal structures of compounds 1–6 were also determined by X‐ray crystallography. Cyclic voltammetry measurements showed that thiols with low oxidation potentials (< 1.0 V) mainly form disulfides upon a reaction with di‐iodine, whereas those with higher oxidation potential form charge transfer (CT), resulting in desulfurated products, MBZIMH. However, in the case of O2N‐MBZIMH a desulfurated species was isolated. The formation of the final product also requires the presence of FeCl3. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:498–511, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21042
Distinct tumor protein p53 mutants in breast cancer subgroups
Authors: Dumay Anne , Feugeas Jean‐Paul , Wittmer Evelyne , Lehmann‐Che Jacqueline , Bertheau Philippe , Espié Marc , Plassa Louis‐François , Cottu Paul , Marty Michel , André Fabrice , Sotiriou Christos , Pusztai Lajos , de Thé Hugues
Published: August 2012

Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes.
Loss of pSer2448‐mTOR expression is linked to adverse prognosis and tumor progression in ERG‐fusion‐positive cancers
Authors: Müller Julia , Ehlers Arne , Burkhardt Lia , Sirma Hüseyin , Steuber Thomas , Graefen Markus , Sauter Guido , Minner Sarah , Simon Ronald , Schlomm Thorsten , Michl Uwe
Published: August 2012

Prevalence and clinical significance of mammalian target of rapamycin (mTOR) phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue microarray containing 3,261 prostate cancers and 49 normal prostate samples with clinical follow‐up data was analyzed for pSer2448‐mTOR expression by immunohistochemistry. Moderate to strong pSer2448‐mTOR staining was found in all (n = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. Moderate and strong staining was found in 36 and 11% of tumors. Loss of pSer2448‐mTOR staining was significantly linked to advanced stage (p = 0.0027), high‐grade (p = 0.0045), nodal positive cancers (p = 0.0483), early tumor recurrence (p < 0.0001, independently from stage and grade, p = 0.0016), lack of Ets‐related gene (ERG) fusion (p < 0.0001), reduced androgen receptor expression (p < 0.0001 each) and increased cell proliferation (p = 0.0092) in all cancers and in the subset of ERG‐fusion‐positive cancers. Loss of pSer2448‐mTOR expression was linked to tumor metastasis (p = 0.0275) in ERG‐fusion‐positive cancers only. Molecular subset analysis using pre‐existing phosphatase and tensin homolog (PTEN) deletion data revealed that loss of pSer2448‐mTOR expression is of prognostic relevance and defines a subpopulation of PTEN‐deleted and ERG‐fusion‐positive cancers with a particular poor outcome. The results of our study strongly suggest that loss of pSer2448‐mTOR expression is a marker for activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated mTOR signaling indicated by loss of pSer2448‐mTOR expression characterize a small (4%) but clinically significant subset of prostate cancers that might optimally benefit from anti‐mTOR therapies.
Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk
Authors: Boucher Beatrice A. , Cotterchio Michelle , Anderson Laura N. , Kreiger Nancy , Kirsh Victoria A. , Thompson Lilian U.
Published: August 2012

Botanical supplements are widely used and contain diverse ingredients, including isoflavones. Food‐based isoflavones have been associated with reduced breast cancer risk. However, no study has comprehensively evaluated supplements identified by isoflavone content and breast cancer risk. Associations between ever use of 28 isoflavone supplements and breast cancer risk in Ontario, Canada were evaluated using cases (n = 3,101) identified in 2002–2003 from the Ontario Cancer Registry and controls (n = 3,471) identified through random digit dialing methods. Multivariate logistic regression was used to estimate age‐adjusted odds ratio (AOR) and 95% confidence intervals (CI). Several individual supplements were associated with reduced breast cancer risk (e.g., Natural HRT; AOR = 0.39; 95% CI: 0.22, 0.69; nusers = 58). Use of any isoflavone supplements was associated with reduced risk when ≥3 were ever used (AOR = 0.68; 95% CI: 0.54, 0.86; nusers = 332; ptrend = 0.008) or any was taken >5 years (AOR = 0.75; 95% CI: 0.60, 0.94; nusers = 325; ptrend = 0.01); high content supplements were consistently associated with reduced risk. Risk reduction was confined to postmenopausal breast cancer for both individual and combined supplements, and was strongest in the latter among high content users who ever took ≥3 supplements (AOR = 0.55; 95% CI: 0.38, 0.81; nusers = 118; ptrend = 0.04) or any >5 years (AOR = 0.47; 95% CI: 0.27, 0.81; nusers = 60; ptrend = 0.03). Associations did not differ by estrogen‐progesterone tumor receptor status. In conclusion, isoflavone supplements were associated with decreased postmenopausal breast cancer risk. Further research to examine these novel findings is warranted, given the low supplement use and potential limitations of our results.
Incidence of childhood cancer among Mexican children registered under a public medical insurance program
Authors: Rivera‐Luna Roberto , Correa‐González Cecilia , Altamirano‐Alvarez Eduardo , Sánchez‐Zubieta Fernando , Cárdenas‐Cardós Rocio , Escamilla‐Asian Gabriela , Olaya‐Vargas Alberto , Bautista‐Marquez Aurora , Aguilar‐Romo Manuel
Published: August 2012

Prior to 2005, 51% of children in Mexico diagnosed with cancer received no standardized optimal multidisciplinary medical care. A government‐subsidized national cancer treatment program was therefore created for these patients and a National Cooperative Childhood Cancer Treatment Group was consequently formed for these patients. Pediatric patients with a proven diagnosis of leukemia, lymphoma or solid tumor and who were registered in the Popular Medical Insurance (PMI) program from January 2007 to December 2010, are described in this report. These patients had been enrolled and registered in one of the 49 nationwide certified medical institutions in Mexico. The national incidence and frequency data for childhood cancers were analyzed for the whole program. At the end of a 4‐year study, the analysis revealed that 8,936 children from across Mexico had been diagnosed with cancer. The incidence rate for the PMI patients was 150.3/million/year (2010) for children of 0–18 years. The highest age incidence rate was 51.9 between 0 and 4 years and boys were the predominant group for all types of cancer. The leukemia incidence was 75.3/million/year (2010), and an average frequency of 50.75% throughout the 4 years. The overall mortality rate was measured at 5.4/100,000/year (2010). This study demonstrates a high frequency and incidence of childhood cancer and a beneficial impact of the PMI program over the quality of life in these children.
A novel role for junctional adhesion molecule‐A in tumor proliferation: Modulation by an anti‐JAM‐A monoclonal antibody
Authors: Goetsch Liliane , Haeuw Jean‐François , Beau‐Larvor Charlotte , Gonzalez Alexandra , Zanna Laurence , Malissard Martine , Lepecquet Anne‐Marie , Robert Alain , Bailly Christian , Broussas Matthieu , Corvaia Nathalie
Published: August 2012

To identify new potential targets in oncology, functional approaches were developed using tumor cells as immunogens to select monoclonal antibodies targeting membrane receptors involved in cell proliferation. For that purpose cancer cells were injected into mice and resulting hybridomas were screened for their ability to inhibit cell proliferation in vitro. Based on this functional approach coupled to proteomic analysis, a monoclonal antibody specifically recognizing the human junctional adhesion molecule‐A (JAM‐A) was defined. Interestingly, compared to both normal and tumor tissues, we observed that JAM‐A was mainly overexpressed on breast, lung and kidney tumor tissues. In vivo experiments demonstrated that injections of anti‐JAM‐A antibody resulted in a significant tumor growth inhibition of xenograft human tumors. Treatment with monoclonal antibody induced a decrease of the Ki67 expression and downregulated JAM‐A levels. All together, our results show for the first time that JAM‐A can interfere with tumor proliferation and suggest that JAM‐A is a potential novel target in oncology. The results also demonstrate that a functional approach coupled to a robust proteomic analysis can be successful to identify new antibody target molecules that lead to promising new antibody‐based therapies against cancers.
EXTRACTIVE MULTINATIONALS AND CORPORATE SOCIAL RESPONSIBILITY: A COMMITMENT TOWARDS ACHIEVING THE GOALS OF SUSTAINABLE DEVELOPMENT OR ONLY A MANAGEMENT STRATEGY?
Authors: Pesmatzoglou Dimitrios , Nikolaou Ioannis E. , Evangelinos Konstantinos I. , Allan Stuart
Published: August 2012

While several decades ago, discussions regarding corporate social responsibility (CSR) were limited to a small group of academics and parts of the business sector; in the recent past, it has grown to become a complex concept with multiple effects and aspects. It is considered to be heavily influential in the decision making of multinational companies. Regarding extractive multinationals, the need for new areas for extraction of natural resources has predictably caused disputes between corporations and local communities, as well as a plethora of environmental considerations. This article contributes to this debate by addressing the issue of whether the CSR of extractive multinationals really contributes to the sustainable development of developing countries. In addition, reasons for CSR not attaining its potential regarding sustainable development are set out and evaluated. Copyright © 2012 John Wiley & Sons, Ltd.
Multiple labeling of a potent CX3CR1 antagonist for the treatment of multiple sclerosis
Authors: Malmquist Jonas , Ström Peter
Published: August 2012

Several methods for the preparation of five isotopologues of the CX3CR1 antagonist 1 were developed. Volatile and radioactive 1‐chloro‐ and 1‐bromo‐ethyl‐benzene was handled in [2′‐14C] and [3′, 5′‐3H] labeling of 1. d‐Leucinol ((R)‐2‐amino‐4‐methylpentan‐1‐ol) was labeled as [1‐14C] and [4‐14C] via a Wittig reaction using Garner's aldehyde and a Strecker amino acid synthesis with d‐acylase resolvation, respectively. A [2H10]d‐leucinol was used for the stable labeled [M + 10] isotopologue. The products were isolated with 97.6–100% stereo chemical and radiochemical purity as for specific activity 768 GBq/mmol and 1.6–2.0 GBq/mmol, respectively.
Validation of a clinical assessment score for pediatric sleep‐disordered breathing
Authors: Goldstein Nira A. , Stefanov Dimitre G. , Graw‐Panzer Katharina D. , Fahmy Samir A. , Fishkin Sherry , Jackson Alison , Sarhis Jennifer S. , Weedon Jeremy
Published: August 2012

Objectives/Hypothesis:

To validate a clinical assessment score for pediatric sleep‐disordered breathing.

Study Design:

Prospective instrument validation.

Methods:

One hundred children scheduled for overnight polysomnography were evaluated by a standardized history and physical examination and assigned a clinical assessment score. Parents completed the Obstructive Sleep Apnea (OSA)‐18, the Pediatric Quality of Life Inventory (PedsQL) 4.0, and the Child Behavior Checklist questionnaires. Children with positive polysomnography underwent adenotonsillectomy or adenoidectomy. The identical assessments were performed at a mean follow‐up of 8 months.

Results:

Item reduction yielded a score of 15 items (Clinical Assessment Score‐15 [CAS‐15]) that demonstrated the best internal consistency and predictive utility (Cronbach α = .80). Intraclass correlation (ICC) demonstrated good intrarater (ICC, 0.78; 95% confidence interval [CI], 0.58 to 0.89) and inter‐rater agreement (ICC, 0.65; 95% CI, 0.26 to 0.84). All change scores were significantly improved after surgery. Effect sizes were large for the CAS‐15 (2.6), OSA‐18 (2.4), and apnea‐hypopnea index (1.4), and moderate for the Child Behavior Checklist (0.7) and PedsQL 4.0 (−0.5). Moderate to strong correlation was found between the initial CAS‐15 scores and the external measures (|r| between 0.32 and 0.65). Receiver operating characteristic curves were constructed to determine the optimal initial CAS‐15 score for predicting positive polysomnography. The area under the curve was 0.77 (95% CI, 0.67 to 0.87); and a score ≥32 yielded a sensitivity of 77.3% (95% CI, 65.3 to 86.7) and a specificity of 60.7% (95% CI, 40.6 to 78.5).

Conclusions:

The CAS‐15 proved useful in an office setting and correctly diagnosed 72% of referred children when compared to polysomnography. It correlated well with external measures and demonstrated a good response to clinical change.
Controlled PEGylation of PLA‐Based Nanoparticles
Authors: Ferrari Raffaele , Yu Yingchuan , Lattuada Marco , Storti Giuseppe , Morbidelli Massimo , Moscatelli Davide
Published: August 2012

The controlled synthesis of degradable nanoparticles (NPs) made from a brush copolymer constituted of a 2‐hydroxyethyl methacrylate (HEMA) backbone with PEG and PLA pendants both tunable in length and composition has been developed. Using ring‐opening polymerization (ROP) of L,L–lactide, vinyl end‐functionalized PLA macromonomers were produced and then copolymerized with HEMA–PEG macromonomers. Narrow dispersed PEGylated NPs with size down to 25 nm with different PEGylation degree and PEG chain lengths were obtained. Surfactant‐free MSSEP in the absence of any solvent was implemented to produce NPs suitable for biomedical applications. The colloidal stability in isotonic solutions of these NPs was investigated and the corresponding critical coagulation concentration (CCC) of the NPs was determined.
Multitargeting by turmeric, the golden spice: From kitchen to clinic
Authors: Gupta Subash C. , Sung Bokyung , Kim Ji Hye , Prasad Sahdeo , Li Shiyou , Aggarwal Bharat B.
Published: August 2012

Although much has been published about curcumin, which is obtained from turmeric, comparatively little is known about turmeric itself. Turmeric, a golden spice obtained from the rhizome of the plant Curcuma longa, has been used to give color and taste to food preparations since ancient times. Traditionally, this spice has been used in Ayurveda and folk medicine for the treatment of such ailments as gynecological problems, gastric problems, hepatic disorders, infectious diseases, and blood disorders. Modern science has provided the scientific basis for the use of turmeric against such disorders. Various chemical constituents have been isolated from this spice, including polyphenols, sesquiterpenes, diterpenes, triterpenoids, sterols, and alkaloids. Curcumin, which constitutes 2–5% of turmeric, is perhaps the most‐studied component. Although some of the activities of turmeric can be mimicked by curcumin, other activities are curcumin‐independent. Cell‐based studies have demonstrated the potential of turmeric as an antimicrobial, insecticidal, larvicidal, antimutagenic, radioprotector, and anticancer agent. Numerous animal studies have shown the potential of this spice against proinflammatory diseases, cancer, neurodegenerative diseases, depression, diabetes, obesity, and atherosclerosis. At the molecular level, this spice has been shown to modulate numerous cell‐signaling pathways. In clinical trials, turmeric has shown efficacy against numerous human ailments including lupus nephritis, cancer, diabetes, irritable bowel syndrome, acne, and fibrosis. Thus, a spice originally common in the kitchen is now exhibiting activities in the clinic. In this review, we discuss the chemical constituents of turmeric, its biological activities, its molecular targets, and its potential in the clinic.
Monte Carlo simulations of Donnan equilibrium in cartilage
Authors: Algotsson Jenny , Åkesson Torbjörn , Forsman Jan
Published: August 2012

23Na magnetic resonance imaging and the delayed gadolinium‐enhanced magnetic resonance imaging methods to investigate cartilage can be used to determine the fixed charge density of cartilage. The methods give results that differ by a factor of 2. In this study, we use Monte Carlo simulations on a model system of cartilage and find that the difference originates from the Coulombic intermolecular interactions between the ions in the cartilage, and in the synovial fluid. Those interactions are neglected in the standard Donnan analysis that generally is adopted to evaluate magnetic resonance imaging data. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Safety of plasma exchange therapy in patients with myasthenia gravis
Authors: Ebadi Hamid , Barth David , Bril Vera
Published: August 2012

Introduction: Plasma exchange (PLEX) is effective in myasthenia gravis (MG), but there are concerns about its safety. Methods: We collected data prospectively from 42 patients randomized to PLEX treatment in a comparison study with intravenous immunoglobulin (IVIg). Detailed information on the PLEX treatment methodology and adverse events are reported. Results: Forty of 42 patients completed PLEX. Ninety percent were treated in an outpatient setting. Fifty‐five percent had no complications, and 45% had mild–moderate reactions that did not require stopping treatment; the majority were citrate reactions and peripheral vascular issues that were easily treated. Fifty‐seven percent of patients responded to treatment, and 83% completed PLEX via peripheral venous access. Two patients had severe adverse events: 1 related and 1 unrelated to PLEX. Comorbid disease and age did not predict reactions. Conclusion: PLEX is safe, effective, and well tolerated in patients with MG. Our results do not raise concerns about the safety of PLEX in patients with moderate–severe MG. Muscle Nerve 47: 510–514, 2013
Eye movement control in reading: Logographic Chinese versus alphabetic scripts
Authors: Tsang Yiu‐Kei , Chen Hsuan‐Chih
Published: August 2012

Eye tracking is widely used to study the reading process in different languages. Given the unique properties of written Chinese, it is important to identify the similarities and differences in eye‐movement controls between readers of Chinese and alphabetic scripts. In this article, we review the data available for comparison in four domains: (a) the perceptual span, (b) parafoveal processing, (c) the basic encoding unit, and (d) computer modeling. Our review indicates that, while some aspects of eye movement control in reading appear to be universal (e.g., the availability of orthographic information in the parafoveal preview), others are more script‐specific (e.g., the size of the perceptual span). It is concluded that the study of cross‐language differences is important for the development of reading models that are generalizable across readers of different scripts.
Nucleophilic substitution reactions promoted by oligoethylene glycols: a mechanistic study of ion‐pair SN2 processes facilitated by Lewis base
Authors: Kim Ju‐Young , Kim Dong Wook , Song Choong Eui , Chi Dae Yoon , Lee Sungyul
Published: August 2012

We present a mechanistic study for nucleophilic substitution (SN2) reactions facilitated by multifunctional n‐oligoethylene glycols (n‐oligoEGs) using alkali metal salts MX (M+ = Cs+, K+, X– = F–, Br–, I–, CN–) as nucleophilic agents. Density functional theory method is employed to elucidate the underlying mechanism of the SN2 reaction. We found that the nucleophiles react as ion pairs, whose metal cation is ‘coordinated’ by the oxygen atoms in oligoEGs acting as Lewis base to reduce the unfavorable electrostatic effects of M+ on X–. The two terminal hydroxyl (−OH) function as ‘anchors’ to collect the nucleophile and the substrate in an ideal configuration for the reaction. Calculated barriers of the reactions are in excellent agreement with all experimentally observed trends of SN2 yields obtained by using various metal cations, nucleophiles and oligoEGs. The reaction barriers are calculated to decrease from triEG to pentaEG, in agreement with the experimentally observed order of efficiency (triEG < tetraEG < pentaEG). The observed relative efficiency of the metal cations Cs+ versus K+ is also nicely demonstrated (larger [better] barrier [efficiency] for Cs+ than for K+). We also examine the effects of the nucleophiles (F–, Br–, I–, CN–), finding that the magnitudes of reaction barriers are F– > CN– > Br– > I–, elucidating the observation that the yield was lowest for F–. It is suggested that the role of oxygen atoms in the promoters is equivalent to that of –OH group in bulky alcohols (tert‐butyl or amyl‐alcohol) for SN2 fluorination reactions previously studied in our lab. Copyright © 2012 John Wiley & Sons, Ltd.
P‐doping of Si nanoparticles: The effect of oxidation
Authors: Carvalho Alexandra , Öberg Sven , Barroso Manuel , Rayson Mark J. , Briddon Patrick
Published: August 2012

The radial dependence of the formation energy of substitutional phosphorus in silicon nanoparticles covered by an amorphous oxide shell is analysed using local density functional theory calculations. It is found that P+ is more stable at the silicon core. This explains the experimental observation of segregation of phosphorus to the Si‐rich regions in a material consisting of Si nanocrystals embedded in a SiO2 matrix [Perego et al., Nanotechnology 21, 025602 (2010)].

magnified image

Formation energy of positively charged substitutional phosphorus in a 1.5 nm diameter Si nanoparticle covered by a ∼2 nm‐thick amorphous SiO2 shell, as a function of its distance to the centre.
Optical nonlinearity in tandem Si‐C photodetectors
Authors: Louro P. , Vieira M. , Vieira M. A.
Published: August 2012

The behavior of tandem pin heterojunctions based on a‐SiC:H alloys is investigated under different optical and electrical bias conditions. The devices are optimized to act as optically selective wavelength filters. Depending on the device configuration (optical gaps, thickness, sequence of cells in the stack structure) and on the applied voltage (positive or negative) and optical bias (wavelength, intensity, frequency) it is possible to combine the wavelength discrimination function with the self amplification of the signal. This wavelength nonlinearity allows the amplification or the rejection of a weak signal‐impulse. The device works as an active tunable optical filter for wavelength selection and can be used as an add/drop multiplexer (ADM) which enables data to enter and leave an optical network bit stream without having to demultiplex the stream. Results show that, even under weak transient input signals, the background wavelength controls the output signal. This nonlinearity, due to the transient asymmetrical light penetration of the input channels across the device together with the modification on the electrical field profile due to the optical bias, allows tuning an input channel without demultiplexing the stream. This high optical nonlinearity makes the optimized devices attractive for the amplification of all optical signals. Transfer characteristics effects due to changes in steady state light, control d.c. voltage and applied light pulses are presented. Based on the experimental results and device configuration an optoelectronic model is developed. The transfer characteristics effects due to changes in steady state light, dc control voltage or applied light pulses are simulated and compared with the experimental data. A good agreement was achieved (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Measurement error and outcomes defined by exceeding a threshold: biased findings in comparative effectiveness trials
Authors: Bůžková Petra
Published: August 2012

In medical studies, the long‐term level of a risk factor exceeding a threshold is often an outcome of interest. In practice, such a risk factor may not be directly measurable. Instead, outcome variables are based on a single or multiple biomedical measurements that have substantial variability. This variability is due to measurement error in a strict sense, true day‐to‐day variability, or a combination of the two. Estimates of prevalence based on such outcomes are biased; some individuals with long‐term levels below the threshold will be diagnosed, and some with long‐term levels above the threshold will not be diagnosed. From a public health point of view, this is a relatively minor concern; it is much less important than the fact that many individuals are not tested at all. However, in comparative effectiveness research studies, such as clinical trials evaluating a new treatment as compared with a placebo or a gold standard treatment, the combination of a noisy measurement and a threshold can distort the studies’ conclusions in important ways. Using simulations and theoretical formulas, we systematically describe the bias of prevalence difference and prevalence ratio when comparing arms and its effect on trial conclusions. Copyright © 2012 John Wiley & Sons, Ltd.
Handling of missing data in long‐term clinical trials: a case study
Authors: Janssens Mark , Molenberghs Geert , Kerstens René
Published: August 2012

Missing data in clinical trials is a well‐known problem, and the classical statistical methods used can be overly simple. This case study shows how well‐established missing data theory can be applied to efficacy data collected in a long‐term open‐label trial with a discontinuation rate of almost 50%. Satisfaction with treatment in chronically constipated patients was the efficacy measure assessed at baseline and every 3 months postbaseline. The improvement in treatment satisfaction from baseline was originally analyzed with a paired t‐test ignoring missing data and discarding the correlation structure of the longitudinal data. As the original analysis started from missing completely at random assumptions regarding the missing data process, the satisfaction data were re‐examined, and several missing at random (MAR) and missing not at random (MNAR) techniques resulted in adjusted estimate for the improvement in satisfaction over 12 months. Throughout the different sensitivity analyses, the effect sizes remained significant and clinically relevant. Thus, even for an open‐label trial design, sensitivity analysis, with different assumptions for the nature of dropouts (MAR or MNAR) and with different classes of models (selection, pattern‐mixture, or multiple imputation models), has been found useful and provides evidence towards the robustness of the original analyses; additional sensitivity analyses could be undertaken to further qualify robustness. Copyright © 2012 John Wiley & Sons, Ltd.
Modelling climate impact on floods with ensemble climate projections
Authors: Cloke Hannah L. , Wetterhall Fredrik , He Yi , Freer Jim E. , Pappenberger Florian
Published: August 2012

The evidence provided by modelled assessments of future climate impact on flooding is fundamental to water resources and flood risk decision making. Impact models usually rely on climate projections from global and regional climate models (GCM/RCMs). However, challenges in representing precipitation events at catchment‐scale resolution mean that decisions must be made on how to appropriately pre‐process the meteorological variables from GCM/RCMs. Here the impacts on projected high flows of differing ensemble approaches and application of Model Output Statistics to RCM precipitation are evaluated while assessing climate change impact on flood hazard in the Upper Severn catchment in the UK. Various ensemble projections are used together with the HBV hydrological model with direct forcing and also compared to a response surface technique. We consider an ensemble of single‐model RCM projections from the current UK Climate Projections (UKCP09); multi‐model ensemble RCM projections from the European Union's FP6 ‘ENSEMBLES’ project; and a joint probability distribution of precipitation and temperature from a GCM‐based perturbed physics ensemble.

The ensemble distribution of results show that flood hazard in the Upper Severn is likely to increase compared to present conditions, but the study highlights the differences between the results from different ensemble methods and the strong assumptions made in using Model Output Statistics to produce the estimates of future river discharge. The results underline the challenges in using the current generation of RCMs for local climate impact studies on flooding. Copyright © 2012 Royal Meteorological Society
A theoretical study of the confinement of methane in water clusters
Authors: Bravo‐Pérez Graciela , Saint‐Martin Humberto
Published: August 2012

A search for stable local minima CH4 ‐ (H2O)n closed methane clathrates was done at the ωB97X‐D/aug‐cc‐pVDZ level of the theory, for n up to 20, starting from various different configurations for each size. The reliability of the method was validated by comparison to the complete basis set limit (CBSL) values of the methane–water interactions, of the water–water interactions and of the binding energies of (H2O)20 clusters. A potential model fitted to reproduce the CBSL interaction energy of the optimal CH4 ‐ (H2O)n pair was also used in Monte Carlo optimizations. Confinement was found to occur already at n = 14. Optimizations with two empirical models for numerical simulations resulted in the same configurations. The addition of more water molecules, though, favored an increase of the size of the cage, instead of making an external hydrogen bond with the other water molecules in the cluster. An analysis was made at the ωB97X‐D/aug‐cc‐pVDZ level of the interactions of methane with the confining clusters. In all cases, the interaction energy was negative, and for the dodecahedral cavity, the confinement of methane resulted in a significant stabilization relative to the unperturbed empty (H2O)20 cluster and an external methane molecule. Another analysis was made of the energetic cost of rotating the methane within the dodecahedral cavity. The corresponding barrier was lower than KBT at ambient temperature. © 2012 Wiley Periodicals, Inc.
Formation control for multi‐agent systems through an iterative learning design approach
Authors: Meng Deyuan , Jia Yingmin
Published: August 2012

This paper deals with formation control problems for multi‐agent systems by using iterative learning control (ILC) design approaches. Distributed formation ILC algorithms are presented to enable all agents in directed graphs to achieve the desired relative formations perfectly over a finite‐time interval. It is shown that not only asymptotic stability but also monotonic convergence of multi‐agent formation ILC can be accomplished, and the convergence conditions in terms of linear matrix inequalities can be simultaneously established. The derived results are also applicable to multi‐agent systems that are subject to stochastic disturbances and model uncertainties. Furthermore, the feasibility of convergence conditions and the effect of communication delays are discussed for the proposed multi‐agent formation ILC algorithms. Simulation results are given for uncertain multi‐agent systems to verify the theoretical study. Copyright © 2012 John Wiley & Sons, Ltd.
A novel user authentication scheme with anonymity for wireless communications
Authors: Niu Jianwei , Li Xiong
Published: August 2012

User authentication and privacy protection are important issues for wireless and mobile communication systems such as GSM, 3G, and 4G wireless networks. Recently, Yoon et al. proposed a user‐friendly authentication scheme with anonymity for wireless communications. However, in this paper, we show that user anonymity of their scheme is not achieved under the eavesdropping attack and their scheme is not fair in the key agreement. In order to ensure security authentication and protect user anonymity for wireless communications, we propose a novel user authentication scheme with anonymity based on elliptic curve cryptosystem, which can resist various known types of attacks and is more practical for wireless and mobile communications. Copyright © 2012 John Wiley & Sons, Ltd.
A simple and robust anonymous two‐factor authenticated key exchange protocol
Authors: Li Xiaowei , Zhang Yuqing
Published: August 2012

Recently two‐factor authenticated key exchange (AKE) protocols have been widely used in various networks to ensure communication security. In 2009, Sun et al. proposed an improved password authenticated key agreement scheme based on smart cards. It is efficient in two‐factor authentication key exchange protocols. However, we found that the scheme of Sun et al. was vulnerable to a password‐guessing attack and a key compromise impersonation (KCI) attack. We made an improvement on the scheme of Sun et al. by using an elegant but simple trick to eliminate the security vulnerabilities. The improved scheme possesses untraceability, which is absent in the scheme of Sun et al. but important in anonymous communication. Moreover, the new scheme can also resist KCI attack, which is a strong secure property in AKE protocol. We proved the security of our protocol in the random oracle model provided that the Elliptic Curve Gap Diffie–Hellman assumption holds. The trick used in this paper can provide a new way for designing authenticated key agreement in two‐factor authentication mechanism. Copyright © 2012 John Wiley & Sons, Ltd.
A novel probabilistic signature based on bilinear square Diffie–Hellman problem and its extension
Authors: Wu Tzong‐Sun , Lin Han‐Yu
Published: August 2012

Digital signatures are just like hand‐written ones, which guarantee integrity, authenticity, and nonrepudiation. On the basis of an intractable mathematical assumption, that is, bilinear square Diffie–Hellman problem, we give a concrete construction of the first provably secure probabilistic signature scheme and its extension to a universal designated verifier signature scheme. A universal designated verifier signature scheme allows any signature holder to designate a publicly verifiable signature to a specific verifier such that only the designated verifier can validate the signature for protecting the privacy of signature holder. In addition, the designated verifier is unable to convince any third party of the fact. Such schemes can be applied to privacy‐preserving electronic applications such as the certificate for medical records and income summary. Our scheme is especially suitable for computation constrained devices because the signature generation and designation are pairing free. Copyright © 2012 John Wiley & Sons, Ltd.
Questionnaire Versus Telephone Follow‐up to Detect Postdischarge Complications in Surgical Patients: Randomized Clinical Trial
Authors: Visser Annelies , Ubbink Dirk T. , Gouma Dirk J. , Goslings J. Carel
Published: August 2012

Background

Postdischarge complications in surgical patients are usually recorded only when readmission is required, a method that likely underestimates the overall complication rate. Our aim was to determine which method—telephone interview or questionnaire by mail—collects the most postdischarge complications.

Methods

We performed a randomized clinical equivalence trial. From December 2008 until August 2009, all adult surgical patients admitted to a university hospital were randomized to be approached by mail or by phone 30 days after discharge to collect information about postdischarge complications. Primary outcome was the total number of reported complications after discharge. Secondary outcome was the severity of the complications.

Results

In all, 1595 patients were reached: 890 by means of a telephone interview and 705 through a questionnaire. Response rate was higher in the telephone group than in the questionnaire group (63.8 % vs. 51.3 %). The percentage of patients reporting one or more complications did not differ significantly between the groups: 43.3 % in the telephone group versus 39.6 % in the questionnaire group. Length of stay, American Society of Anesthesiologist class, and type of surgery—but not the survey techniques compared here—significantly influenced the number of complications reported. The percentage of patient‐reported complications requiring treatment did not differ significantly between the groups.

Conclusions

The two survey methods did not differ in their ability to appreciate postdischarge complications as reported by the patients. The decision to use either method may be determined by the institution, costs involved, and labor requirement.
Accelerated establishment of mature signaling patterns following stimulation of developing neuronal networks: “learning” versus “plasticity”
Authors: Zemianek Jill M. , Lee Sangmook , Guaraldi Mary , Shea Thomas B.
Published: August 2012

Neuronal networks established on micro‐electrode arrays provide useful models for synaptic plasticity. Whether or not this represents a facet of learning is debated since ex vivo networks are deprived of organismal interaction with the environment. We compared developmental signaling of such networks with and without stimulation with a prerecorded synaptic signal from another mature culture as a model of sensory input. Unstimulated networks displayed a developmental increase in individual signals that eventually declined, yielding a pattern containing organized bursts of signaling. Minimal stimulation, to model the onset of sensory input hastened the onset of developmental signaling. However, the overall developmental pattern of stimulated networks, including the total number and type of signals as well as the length of this developmental period, was identical to that of unstimulated networks. One interpretation of these findings is that ongoing plasticity may be essential to establish an appropriate platform for learning once sensory input ensues.
Effects of PTEN inhibition on regulation of tau phosphorylation in an okadaic acid‐induced neurodegeneration model
Authors: Chen Zhou , Chen Bin , Xu Wen‐Fang , Liu Rong‐Fang , Yang Jian , Yu Chang‐Xi
Published: August 2012

One of pathological hallmarks of Alzheimer's disease (AD) is neurofibrillary tangles (NFTs) consisting of abnormally hyperphosphorylated tau. The molecular mechanisms underlying the regulation of tau hyperphosphorylation remain largely unclear. The phosphoinositide 3‐kinase (PI3K)/Akt pathway has been implicated in the pathogenesis of AD, however, potential functions and role of tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in AD pathogenesis have not been fully explored. Here, we report that okadaic acid (OA)‐induced tau phosphorylation is accompanied by PTEN induction, knockdown of PTEN reduces the tau hyperphosphorylation by OA in SH‐SY5Y cells and increases cell proliferation and survival. The effect of PTEN suppression on tau dephosphorylation appeared to be mediated by inhibition of glycogen synthase kinase 3 while enhancing the Akt activity. Reduction of tau phosphorylation was also observed in the OA‐induced parental SH‐SY5Y cells co‐treated with bisperoxovanadate (bpv), a potent PTEN inhibitor. Our studies provide evidence for an effect of PTEN on the phosphorylation of tau in AD pathogenesis and give some insight into the mechanisms through which suppression of PTEN expression may contribute towards the amelioration of tauopathy, implying that pharmacological intervention of PTEN may be a new therapeutic approach for the treatment of AD.
Russian brain drain: Myths v. reality
Authors: Korobkov Andrei V. , Zaionchkovskaia Zhanna A.
Published: August 2012

The paper analyzes the scale and dynamics of the Russian brain drain, one of the most politicized and hotly debated aspects of the post-Soviet migration. The major issues under consideration include the durability of the intellectual migration flow, its structural characteristics, and territorial orientation.

Relying on the Russian State Committee on Statistics data, the research indicates that the real scale of intellectual migration is significantly smaller than is usually expected, even though in some regions and particular fields of Basic Sciences, including Mathematics, Physics, Biology, and Chemistry, and a limited number of research centers, brain drain has indeed acquired a magnitude threatening the existence of the established academic schools. At the same time, huge disparities in terms of the ability of specialists from different branches of science to find adequate jobs abroad are evident. Many academic subfields, including Humanities and Social Sciences, and most of the Russian regions show extremely low levels of intellectual migration and engagement in the international academic exchanges. The result is the practical exclusion of many branches of science and the majority of the Russian regions from the international academic system.

Hence the goal of the Russian policy should be not limiting the intellectualmigration, but rather capitalizing on such of its positive aspects as the establishment of long term international academic contacts and the formation of the Russian elite diasporas abroad, actively engaged in cooperationwith the RF academic institutions. Of special interest for the authors are the recent attempts by the RF leadership to encourage the return of the Russian academics. The authors conclude that a more effective policy could be based on the use of diverse forms of cooperationwith the Russian academics abroad, both with or without their permanent relocation to the country, providing for the inclusion of the Russian science into the international academic networks.
Rogue Cops’ Politics of Equality inThe Wire
Authors: KIM YOUNGHOON
Published: August 2012

This paper explores HBO television showThe Wire's portrayal of inequality and injustice in terms of the neoliberal state and capitalism, while focussing on the Baltimore Police Department and the marginalized people in the show. In arguing that the neoliberal state and neoliberalism promote the systemic problems reflected inThe Wire, this paper will examine the representation of the marginalized in the show in relation to Zygmunt Bauman's idea of wasted lives. In doing so, it will explore how bureaucracies in the show fail to salvage the wasted lives that Bauman defines as the collateral casualties of capitalistic globalization. After examining the show's bleak portrayal of American urban life in terms of the police department, this paper will discuss some morally complicated characters, such as Major Colvin and Detectives McNulty and Freamon, who attempt to surmount the systemic problems of the department. In examining their controversial police work, including transgressions of law, this paper aims to clarify the political implications of these police officers in terms of Jacques Rancière's ideas of politics and equality.
State Capacity and Bureaucratic Autonomy in the Early United States: The Case of the Army Corps of Topographical Engineers
Authors: Adler William D.
Published: August 2012

This article reconsiders early American state capacity through a close examination of the U.S. Army Corps of Topographical Engineers. The topographical corps, a bureau in the antebellum War Department, developed a form of conditional bureaucratic autonomy far earlier than recognized in previous scholarship, giving it a central role in shaping national economic development policies, especially in the nation's periphery. Unlike robust bureaucratic autonomy, such as that described by Daniel Carpenter (2001, 2010; see footnote 4), conditional autonomy is highly contingent and can quickly fracture if the surrounding environment changes. The long-serving chief of the corps, Col. John J. Abert, shaped the opinions of his supposed principals by managing the ideas, information, and proposals directed to them. When faced with challenges, the corps proved to be a flexible organization that adapted its methods to accomplish its preferred ultimate goals using different instruments. In the end, however, the corps' autonomy was threatened when it became involved in the sectional politics surrounding the potential building of a transcontinental railroad line. Once the corps lost several of the conditions supporting its autonomy, its downfall was swift. This article thus joins a recent wave of scholarship highlighting strengths within the early American state by foregrounding the role of the armed forces in statebuilding.