bluuebunny/crossref_metadata_2025 huggingface dataset:
The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS)
Authors: Newman Connie B , Szarek Michael , Colhoun Helen M , Betteridge D John , Durrington Paul N , Hitman Graham A , Neil H Andrew W , Demicco David A , Auster Sheila , Fuller John H
Published: September 2008

The objective of this study was to evaluate the safety and tolerability of atorvastatin 10 mg compared with placebo in 2,838 patients with type 2 diabetes and no history of coronary heart disease who were enrolled in the Collaborative Atorvastatin Diabetes Study (CARDS) and followed for 3.9 years.

The percentages of patients experiencing treatment-associated adverse events (AEs), serious AEs and discontinuations due to AEs in the atorvastatin (n=1,428) and placebo (n=1,410) groups were 23.0% vs. 25.4%, 1.1% vs. 1.1% and 2.9% vs. 3.4%, respectively. The most common treatment-associated AEs in the atorvastatin and placebo groups were digestive system-related (8.9% vs. 10.0%). All-cause and treatment-associated myalgia were reported in 4.0% and 1.0% of atorvastatin-treated patients, and 4.8% and 1.2% of placebo-treated patients. An analysis of selected AEs by tertiles of baseline low-density lipoprotein (LDL) cholesterol showed no relationship between LDL cholesterol levels and the incidence of myalgia, cancer or nervous system AEs in either treatment group.

Overall, these data demonstrate that atorvastatin 10 mg was well tolerated in patients with type 2 diabetes during long-term treatment.
Natural Resource Management
Authors: Fox David R.
Published: September 2008

The management of natural assets is a daunting and difficult job. Increasingly, natural resource managers are turning to risk‐based approaches as an adjunct to the decision‐making process. While not infallible, risk analysis provides a more strategic, comprehensive, and scientifically defensible approach to decision making about highly complex and uncertain natural management issues.
Multistate Models for Life Insurance Mathematics
Authors: Norberg Ragnar
Published: September 2008

The subject matter and methodology of modern life insurance mathematics are surveyed in the framework of a multistate model for life‐history analysis. Standard insurance products with payments depending only on life‐ history events are described and analyzed in the commonly used Markov chain model under the assumption of deterministic interest rates. The actuarial equivalence principle for determining premiums and reserves is motivated by risk diversification in large portfolios. Differential equations for reserves and other conditional expected values are obtained and proclaimed basic, constructive, and computational tools. The traditional method for managing nondiversifiable risk arising from changes in e.g., mortality rates and interest rates is outlined; premiums are calculated under prudent assumptions, and systematic surpluses thus created are repaid as bonus. An alternative way of managing nondiversifiable risk is to link the contractual payments to the development of mortality, interest, and possibly other demographic or economic indexes. Examples of so‐called index‐linked products are given, and premiums and reserves are determined by combined use of classical actuarial principles and principles of pricing and hedging from financial mathematics. Transfer of nondiversifiable risk to the financial markets through creation of tradeable insurance derivatives is outlined as an idea. The present article is a revised and shortened version of an entry in the Encyclopedia of Actuarial Science published by Wiley in 2004.
Model Risk
Authors: Crouhy Michel , Galai Dan , Mark Robert
Published: September 2008

Models are an inevitable feature of modern finance, and model risk is inherent in the use of models. In this article we stress the technical elements of model risk. Models are susceptible to errors: from incorrect assumptions about price dynamics and market interactions, from implementing a model wrongly, from inaccurate estimation of volatilities and correlations and other inputs that are not directly observable and must be forecasted. We also discuss how to mitigate model risk.
Continuous‐Time Asset Allocation
Authors: Zhou Xun Yu
Published: September 2008

This article describes the two main approaches, called the primal (forward) and the dual (backward) ones, to the two predominant asset allocation models in continuous time, namely, those of expected utility maximization and the mean–variance.
Cost‐Effectiveness Analysis
Authors: Fenwick Elisabeth A.L. , Briggs Andrew H.
Published: September 2008

In a resource‐limited environment, it is important to determine whether a proposed health program represents a good use of scarce resources (money, labor, land, capital, etc.). Economic evaluation provides a framework to approach and inform difficult decisions about the best use of limited resources, through an assessment of both the costs and outcomes associated with a proposed program. This article first examines the foundations of economic evaluation in welfare economic theory and cost‐benefit analysis. The article then moves quickly on to a presentation of cost‐effectiveness analysis incorporating a discussion of incremental cost‐effectiveness decision rules, methods for handling uncertainty, and the use of value of information for decision making. The article focuses on the requirements of a health care policy maker attempting to determine whether to reimburse a health care technology given the information and uncertainty surrounding the decision. In addition, the article examines how the policy maker might approach the choice about whether to request further research to inform the decision. A stylized case study is used to illustrate the concepts and approach. The article links with those on decision analysis, uncertainty analysis, and value of information analysis.
Uncertainty and Variability Characterization and Measures in Risk Assessment
Authors: Rai Shesh N.
Published: September 2008

Probabilistic risk characterization, which is now commonly used to model risk and exposure, involves identifying sources of variations. We characterize risk as a function of risk factors. The distribution of any risk factor depends on two sources of heterogeneity (dispersion): uncertainty and variability. Uncertainty represents the degree of ignorance about the precise value of a particular parameter of a distribution. Variability represents inherent variation within the population of interest. We give an example to demonstrate uncertainty and variability that is based on a multiplicative model of risk due to contaminated drinking water.
Approaches for assessing the role of household socioeconomic status on child anthropometric measures in urban South Africa
Authors: Sheppard Zoë A. , Norris Shane A. , Pettifor John M. , Cameron Noël , Griffiths Paula L.
Published: September 2008

The objectives of this article were to compare the variance explained in anthropometric outcomes when using individual measures of socioeconomic status (SES) versus different approaches to create SES indices within the urban African context, and to examine the influence of SES measured during infancy on child anthropometric outcomes at 7/8 years. Data from the 1990 Birth‐to‐Twenty cohort study set in Johannesburg‐Soweto, South Africa, were used (n = 888). Linear regression models were used to investigate the association between SES (individual and index measures) during infancy and anthropometric measures at age 7/8 years, controlling for sex, age, and population group. Both individual and index measures of SES explained similar proportions of the variance for each anthropometric outcome. SES measured during infancy influenced weight more than height at age 7/8 years in Johannesburg‐Soweto. Positive associations were found between SES and the anthropometric measures––ownership of a car, telephone, and having an inside flush toilet were the most significant SES variables. The similarities observed in the variance explained relating to the anthropometric outcomes suggest that researchers who want to adjust for SES in analyses could use an SES index to make statistical models more parsimonious. However, using such indices loses information relating to the specific socioeconomic factors that are important for explaining child anthropometrics. If the purpose of the research is to make policy recommendations for the improvement of child growth, individual SES variables would provide more specific information to target interventions. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.
Attention deficit hyperactivity disorder in obese melanocortin‐4‐receptor (MC4R) deficient subjects: A newly described expression of MC4R deficiency
Authors: Agranat‐Meged Anat , Ghanadri Yoad , Eisenberg Iris , Ben Neriah Ziva , Kieselstein‐Gross Eva , Mitrani‐Rosenbaum Stella
Published: September 2008

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous highly heritable disorder which has recently been described to be comorbid in obese subjects. This study investigated phenotype/genotype associations in a consanguineous family with genetic obesity due to the melanocortin‐4‐receptor (MC4R) (C271R) mutation. MC4R deficiency disrupts hunger/satiety regulation resulting in abnormal eating behaviors. To date, the behavioral/psychiatric characteristics of MC4R deficiency have not been described except for a possible association with Binge Eating Disorder. Twenty‐nine subjects of a family known to carry the MC4R (C271R) mutation, were genotyped for the mutation and underwent extensive evaluations in search for physical/psychiatric phenotype characteristics. Subjects originated from proband nuclear families with morbid obese children (BMI percentile > 97%). All probands were homozygous for the MC4R (C271R) mutation. ADHD prevalence was higher than expected only in the groups carrying the homozygous or heterozygous mutation (P = 0.00057, 0.0028, respectively). An obvious difference was observed between the homozygous group and the rest of the family in terms of obesity: homozygous subjects had childhood morbid obesity whereas heterozygous subjects included lean, normal weight and later onset obese subjects. A significant difference was found in ADHD prevalence between the homozygous MC4R (C271R) group (80%) and the rest of the family (22%) (P = 0.033) and a significant trend was found between ADHD prevalence and the number of MC4R (C271R) alleles (P = 0.0267). We conclude that in our sample, the MC4R (C271R) mutation causing obesity, is in association with ADHD. Identifying specific subgroups in which the comorbidity of obesity and ADHD occur may contribute to the understanding of the underlying molecular mechanisms. © 2008 Wiley‐Liss, Inc.
Effects of L‐phenylalanine as a nucleation agent on the nonisothermal crystallization, melting behavior, and mechanical properties of poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate)
Authors: Luo Rongcong , Xu Kaitian , Chen Guoqiang
Published: September 2008

Poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBHHx) is a thermoplastic biopolyester with a slow crystallization rate. L‐Phenylalanine (L‐PH) was used to improve the crystallization rate of PHBHHx. The nonisothermal crystallization kinetics and melting behaviors of PHBHHx and PHBHHx/L‐PH samples were characterized and compared with differential scanning calorimetry. At cooling rates of 2, 5, 10, and 20°C/min, PHBHHx/L‐PH could crystallize at higher temperatures than pure PHBHHx. A modified Avrami equation based analysis showed that the addition of L‐PH shortened the half‐time of crystallization of PHBHHx from 9.6 to 8.0 min and increased the composite rate constant of PHBHHx from 0.201 to 0.283 during the nonisothermal crystallization process at a cooling rate of 10°C/min. For other cooling rates, similar trends of changes were observed. These indicated a faster crystallization rate of PHBHHx in the presence of L‐PH. PHBHHx/L‐PH samples showed a higher melting temperature and a sharper melting peak than those of the pure PHBHHx, which suggested that L‐PH as a nucleation agent improved the perfection of the PHBHHx crystals. Stress–strain measurements showed that both PHBHHx and PHBHHx/L‐PH maintained their ductile and elastic properties during the 60 days of the aging study. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
A biodegradable diblcok copolymer poly(ethylene glycol)‐block‐poly(L‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylene carbonate): Docetaxel and RGD conjugation
Authors: Xie Zhigang , Hu Xiuli , Chen Xuesi , Lu Tiancheng , Liu Shi , Jing Xiabin
Published: September 2008

A diblcok copolymer monomethoxy poly (ethyleneglycol)‐block‐poly(L‐lactide‐co‐2‐methyl‐2‐carboxyl‐propylene carbonate) (MPEG‐b‐P(LA‐co‐MCC)) was obtained by copolymerization of L‐lactide (LA) and 2‐methyl‐2‐benzoxycarbonyl‐propylene carbonate (MBC) and subsequent catalytic hydrogenation. The pendant carboxyl groups of the copolymer MPEG‐b‐P(LA‐co‐MCC) were conjugated with antitumor drug docetaxel and tripeptide arginine‐glycine‐aspartic acid (RGD), respectively. 1H‐NMR spectra confirmed the structure of the copolymer MPEG‐b‐P(LA‐co‐MCC/docetaxel) and MPEG‐b‐P(LA‐co‐MCC/RGD). In vitro antitumor assay indicates that the MPEG‐b‐P(LA‐co‐MCC/docetaxel) conjugate shows high cytotoxic activity against HeLa cancer cells. Cell adhesion and spreading experiment shows that copolymer MPEG‐b‐P(LA‐co‐MCC/RGD) is of benefit to cell adherence and is a promising biodegradable material for cell and tissue engineering. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
“The great good place” where the great want is met: psychoanalytic reflections on the short story by Henry James
Authors: Young Barbara
Published: September 2008

Henry James (1843–1916) was a prolific storyteller who supported himself by his writing. During times of frustration and disappointment, he would become depressed. His therapy was to keep busy with his pen. Though much of his writing is difficult to read, his astute observations of people's psychological functioning make the reading all worthwhile. In his later years, beginning with this story, he became more self observant, and his stories increasingly draw on his own childhood emotional experiences and become cautionary tales about how best to live one's life. This story precedes “The Beast in the Jungle” by five years. Dr Young's paper on that novella was published in this journal in 2007. Copyright © 2008 John Wiley & Sons, Ltd.
Scholarly hyperwriting: The function of links in academic weblogs
Authors: Luzón María José
Published: September 2008

Weblogs are gaining momentum as one of most versatile tools for online scholarly communication. Since academic weblogs tend to be used by scholars to position themselves in a disciplinary blogging community, links are essential to their construction. The aim of this article is to analyze the reasons for linking in academic weblogs and to determine how links are used for distribution of information, collaborative construction of knowledge, and construction of the blog's and the blogger's identity. For this purpose I analyzed types of links in 15 academic blogs, considering both sidebar links and in‐post links. The results show that links are strategically used by academic bloggers for several purposes, among others to seek their place in a disciplinary community, to engage in hypertext conversations for collaborative construction of knowledge, to organize information in the blog, to publicize their research, to enhance the blog's visibility, and to optimize blog entries and the blog itself.
Selective Propargylation of Carbonyl Compounds and Imines with Barium Reagents
Authors: Yanagisawa Akira , Suzuki Takahiro , Koide Takanori , Okitsu Shogo , Arai Takayoshi
Published: September 2008

A Barbier‐type regioselective propargylation of aldehydes and ketones with (3‐bromobut‐1‐ynyl)trimethylsilane has been achieved using reactive barium as a low‐valent metal in THF. Especially in the case of ketones, the corresponding homopropargylic alcohols form almost exclusively. In the reaction of α,β‐unsaturated carbonyl compounds, only 1,2‐adducts have been observed. This method is also applicable to propargylation of imines, and the corresponding homopropargylic amines are obtained regiospecifically in good yields with diastereomeric ratios of up to 87:13.
Increased risks of infant mortality and of deaths due to congenital malformation in the offspring of male electronics workers
Authors: Sung Tzu‐I , Wang Jung‐Der , Chen Pau‐Chung
Published: September 2008

BACKGROUND:

There is limited evidence on the association between paternal occupational exposure during preconception and infant mortality and deaths due to congenital malformation. This retrospective cohort study was conducted to determine if such an association existed among male workers employed in an electronics factory.

METHODS:

We linked the databases of labor insurance, birth registration, and national death registry, identified 7,202 male workers ever employed in this factory with 13,592 liveborn children and 81 deaths in the first year after, excluding 861 children with potential maternal exposure from the same workplace. Fathers employed in this factory during their preconceptional periods (3 months prior to the conception) were considered as exposed compared with those not employed during the same periods. Poisson regression models were constructed to adjust for potential confounding by child's sex, parity, multiple births, year of birth, parental age at delivery, and educational levels.

RESULTS:

Based on 24 exposed cases, the rate ratios (RRs) of infant mortality were increased to 5.06 (95% CI: 2.33–11.00) and 2.81 (95% CI: 1.44–5.51) among liveborn children whose fathers worked for >10 and 1–10 years, respectively, in this factory during preconception. Maternal delivery age less than 20 years, fathers with less than 10 years of education, and multiple births were associated with increased risks of infant mortality. When limited to 28 deaths with congenital malformation, Poisson regression model showed an increased risk for exposed pregnancies (RR = 3.75; 95% CI: 1.29–10.94), especially among cardiac defects (RR = 5.06; 95% CI: 1.58–16.19).

CONCLUSIONS:

Our study suggests that paternal occupational exposures, possibly to organic solvents during preconception, might increase infant mortality and deaths due to congenital malformation, especially for cardiac defects. However, the small numbers of this study limited the generalization of its findings. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Culture nutrition and physiology impact the inhibitor tolerance of the yeastPichia stipitisNRRL Y‐7124
Authors: Slininger Patricia J. , Gorsich Steven W. , Liu Zonglin L.
Published: September 2008

Pichia stipitisNRRL Y‐7124 is one of the natural yeasts best able to utilize biomass because it is able to ferment hexoses and the pentose, xylose, to economically recoverable concentrations of ethanol. To test the impact of culture conditions on inhibitor tolerance, inhibitors were spiked to growing or stationary‐phaseP. stipitissupplied either glucose or xylose and varying nitrogen and mineral compositions; then the ensuing specific death rate response was measured. Resistance of glucose‐ or xylose‐grown cells to inhibitors was generally greater in stationary‐phase cells than log‐phase cells, despite a greater exposure of stationary cells to ethanol. Consistent with this, the specific productivity of detoxification products, furan methanol or furan‐2,5‐dimethanol, from respective spikes of furfural or HMF increased as cultures progressed into stationary phase. However, when xylose was the substrate, ethanol resistance behaved uniquely and was greater for log‐ than stationary‐phase cells. Amino acid enrichment of the growth medium significantly enhanced ethanol tolerance if xylose was the carbon source, but had no impact if glucose supplied carbon. Regardless of the carbon source, amino acid enrichment of the culture medium enhanced the ability of cells to resist furfural and HMF exposure. Mineral compositions tested had little impact on inhibitor resistance except stationary‐phase xylose‐grown cells were more susceptible to inhibitor exposure when magnesium sulfate was excessive. Observed tolerance optimization based on specific death rate as a function of culture physiological state, carbon source, nitrogen source and mineral composition provides new knowledge supporting process designs to convert biomass to ethanol usingP. stipitis. Biotechnol. Bioeng. 2009; 102: 778–790. © 2008 Wiley Periodicals, Inc.
An efficient and scalable process for helper‐dependent adenoviral vector production using polyethylenimine‐adenofection
Authors: Dormond E. , Meneses‐Acosta A. , Jacob D. , Durocher Y. , Gilbert R. , Perrier M. , Kamen A.
Published: September 2008

Safety requirements for adenoviral gene therapy protocols have led to the development of the third generation of vectors commonly called helper‐dependent adenoviral vectors (HDVs). HDVs have demonstrated a high therapeutic potential; however, the poor efficiency and reliability of the actual production process hampers further large‐scale clinical evaluation of this new vector. The current HDV production methods involve a preliminary rescue step through transfection of adherent cell cultures by an HDV plasmid followed by a helper adenovirus (HV) infection. Amplification by serial co‐infection of complementary cells allows an increase in the HDV titer. Using a HEK293 FLP/frt cell system in suspension culture, an alternative protocol to the current transfection/infection procedure was evaluated. In this work, the adenofection uses the HDV plasmid linked to the HV with the help of polyethylenimine (PEI) and has shown to outperform standard protocols by producing higher HDV yield. The influence of complex composition on the HDV production was examined by a statistical design. The optimized adenofection and amplification conditions were successively performed to generate HDV at the 3 L bioreactor scale. Following only two serial co‐infection passages, up to 1.44 × 108 HDV infectious units/mL of culture were generated, which corresponded to 26% of the total particles produced. This production strategy, realized in cell suspension culture, reduced process duration and therefore the probability of vector recombination by introducing a cost‐effective transfection protocol, ensuring production of high‐quality vector stock. Biotechnol. Bioeng. 2009; 102: 800–810. © 2008 Wiley Periodicals, Inc.
The use of oxygen uptake rate to monitor discovery of microbial and enzymatic biocatalysts
Authors: Dumsday Geoff J. , Ocal Gunseli , Bridger John S. , Zachariou Michael
Published: September 2008

Arising from the requirement for discovery of novel biocatalysts with unusual properties, a process was developed which uniquely combines aspects of continuous culture with the measurement of oxygen uptake. This adaptation of the chemostat can be used to facilitate the isolation of a number of microorganisms with desirable properties, particularly those with useful metabolic capabilities and/or enzymes. The technique was also used to provide feedback on the metabolic status of a microbial population and increase the feed flow rate (i.e., dilution rate) thereby enabling the isolation of microorganisms with enhanced 1,3‐propanediol dehydrogenase activity. The use of oxygen uptake as an indicator of cellular activity enables indirect measurement of substrate utilization and provides a real‐time online assessment of the status of microbial enrichment or evolutionary processes and provides an opportunity, through the use of feedback systems, to control these processes. To demonstrate the utility of the technique, oxygen uptake rate (OUR) was compared with a range of conventional analytical techniques that are typically used to monitor enrichment/evolutionary processes and showed good correlation. Further validation was demonstrated by monitoring a characterizable microbial population shift using OUR. The population change was confirmed using off‐line analytical techniques that are traditionally used to determine microbial activity. OUR was then used to monitor the enrichment of microorganisms capable of using a solvent (1‐methyl‐2‐pyrrolidinone) as the sole source of carbon for energy and biomass formation from a heterogeneous microbial population. After purification the microorganisms taken from the enrichment process were able to completely utilize 1 g L−1 1‐methyl‐2‐pyrrolidinone within 24 h demonstrating that the technique had correctly indicated the enriched population was capable of growth on 1‐methyl‐2‐pyrrolidinone. The technique improves on conventional microbial enrichment that utilizes continuous culture by providing a real‐time assessment of the enrichment process and the opportunity to use the OUR output for automated control and variation of one or more growth parameters. Biotechnol. Bioeng. 2009;102: 673‐683. © 2008 Wiley Periodicals, Inc.
Relevance vector machines for multivariate calibration purposes
Authors: Hernández Noslen , Talavera Isneri , Dago Angel , Biscay Rolando J. , Ferreira Marcia M. Castro , Porro Diana
Published: September 2008

The introduction of support vector regression (SVR) and least square support vector machines (LS‐SVM) methods for regression purposes in the field of chemometrics has provided advantageous alternatives to the existing linear and nonlinear multivariate calibration (MVC) approaches. Relevance vector machines (RVMs) claim the advantages attributed to all the SVM‐based methods over many other regression methods. Additionally, it also exhibits advantages over the standard SVM‐based ones since: it is not necessary to estimate the error/margin trade‐off parameterCand the insensitivity parameter ε in regression tasks, it is applicable to arbitrary basis functions, the algorithm gives probability estimates seamlessly and offer, additionally, excellent sparseness capabilities, which can result in a simple and robust model for the estimation of different properties. This paper presents the use of RVMs as a nonlinear MVC method capable of dealing with ill‐posed problems. To study its behavior, three different chemometric benchmark datasets are considered, including both linear and non‐linear solutions. RVM was compared with other calibration approaches reported in the literature. Although RVM performance is comparable with the best results obtained by LS‐SVM, the final model achieved is sparser, so the prediction process is faster. Taking into account the other advantages attributed to RVMs, it can be concluded that this technique can be seen as a very promising option to solve nonlinear problems in MVC. Copyright © 2008 John Wiley & Sons, Ltd.
Is the Hoveyda–Grubbs Complex a Vinylogous Fischer‐Type Carbene? Aromaticity‐Controlled Activity of Ruthenium Metathesis Catalysts
Authors: Barbasiewicz Michał , Szadkowska Anna , Makal Anna , Jarzembska Katarzyna , Woźniak Krzysztof , Grela Karol
Published: September 2008

Three naphthalene‐based analogues (4 a–c) of the Hoveyda–Grubbs metathesis catalyst exhibited immense differences in reactivity. Systematic structural and spectroscopic studies revealed that the ruthenafurane ring present in all 2‐isopropoxyarylidene chelates possesses some aromatic character, which inhibits catalyst activity. This aromatic stabilization within the chelate ring may be controlled by variation of the polycyclic core topology as was demonstrated for tetraline and phenanthrene derivatives (4 d, e). General conclusions about a new mode of ligand‐structure tuning in catalytic systems are presented.
A Convergent Approach to Biocompatible Polyglycerol “Click” Dendrons for the Synthesis of Modular Core–Shell Architectures and Their Transport Behavior
Authors: Wyszogrodzka Monika , Haag Rainer
Published: September 2008

Dendrimers are an important class of polymeric materials for a broad range of applications in which monodispersity and multivalency are of interest. Here we report on a highly efficient synthetic route towards bifunctional polyglycerol dendrons on a multigram scale. Commercially available triglycerol (1), which is highly biocompatible, was used as starting material. By applying Williamson ether synthesis followed by an ozonolysis/reduction procedure, glycerol‐based dendrons up to the fourth generation were prepared. The obtained products have a reactive core, which was further functionalized to the corresponding monoazido derivatives. By applying copper(I)‐catalyzed 1,3‐dipolar cycloaddition, so‐called “click” coupling, a library of core–shell architectures was prepared. After removal of the 1,2‐diol protecting groups, water‐soluble core–shell architectures 24–27 of different generations were obtained in high yields. In the structure–transport relationship with Nile red we observe a clear dependence on core size and generation of the polyglycerol dendrons.
Novel Guanidine‐Containing Molecular Transporters Based on Lactose Scaffolds: Lipophilicity Effect on the Intracellular Organellar Selectivity
Authors: Biswas Goutam , Jeon Ock‐Youm , Lee Woo Sirl , Kim Dong‐Chan , Kim Kyong‐Tai , Lee Suho , Chang Sunghoe , Chung Sung‐Kee
Published: September 2008

We have synthesized two lactose‐based molecular transporters, each containing seven guanidine residues attached to the lactose scaffold through ω‐aminocarboxylate linker chains of two different lengths, and have examined their cellular uptakes and intracellular and organellar localizations in HeLa cells, as well as their tissue distributions in mice. Both molecular transporters showed higher cellular uptake efficiencies than Arg8, and wide tissue distributions including the brain. Mitochondrial localization is of special interest because of its potential relevance to “mitochondrial diseases”. Interestingly, it has been found that the intracellular localization sites of the G7 molecular transporters—namely either mitochondria or lysosomes and endocytic vesicles—are largely determined by the linker chain lengths, or their associated lipophilicities.
Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice
Authors: Li Wen‐Lei , Yu Shan Ping , Ogle Molly E. , Ding Xin Sheng , Wei Ling
Published: September 2008

Peripheral stimulation and physical therapy can promote neurovascular plasticity and functional recovery after CNS disorders such as ischemic stroke. Using a rodent model of whisker‐barrel cortex stroke, we have previously demonstrated that whisker activity promotes angiogenesis in the penumbra of the ischemic barrel cortex. This study explored the potential of increased peripheral activity to promote neurogenesis and neural progenitor migration toward the ischemic barrel cortex. Three days after focal barrel cortex ischemia in adult mice, whiskers were manually stimulated (15 min × 3 times/day) to enhance afferent signals to the ischemic barrel cortex. 5‐Bromo‐2′‐deoxyuridine (BrdU, i.p.) was administered once daily to label newborn cells. At 14 days after stroke, whisker stimulation significantly increased vascular endothelial growth factor and stromal‐derived factor‐1 expression in the penumbra. The whisker stimulation animals showed increased doublecortin (DCX) positive and DCX/BrdU‐positive cells in the ipsilateral corpus of the white matter but no increase in BrdU‐positive cells in the subventricular zone, suggesting a selective effect on neuroblast migration. Neurogenesis indicated by neuronal nuclear protein and BrdU double staining was also enhanced by whisker stimulation in the penumbra at 30 days after stroke. Local cerebral blood flow was better recovered in mice that received whisker stimulation. It is suggested that the enriched microenvironment created by specific peripheral stimulation increases regenerative responses in the postischemic brain and may benefit long‐term functional recovery from ischemic stroke. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Lewis Base Adducts of Heavier Group 13 Halohydrides – Not Just Aspiring Trihydrides!
Authors: Alexander Sean G. , Cole Marcus L.
Published: September 2008

The chemistries of the heavier group 13 halohydrides have been scarcely studied relative to those of their trihydride and trihalide counterparts. This short review summarises the literature concerning these compounds and seeks to highlight their distinct reactivities such that they may find increasing application in other fields of science. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Optimal sampling frequency for volatility forecast models for the Indian stock markets
Authors: Bhattacharyya Malay , Kumar M Dileep , Kumar Ramesh
Published: September 2008

This paper evaluates the performance of conditional variance models using high‐frequency data of the National Stock Index (S&P CNX NIFTY) and attempts to determine the optimal sampling frequency for the best daily volatility forecast. A linear combination of the realized volatilities calculated at two different frequencies is used as benchmark to evaluate the volatility forecasting ability of the conditional variance models (GARCH (1, 1)) at different sampling frequencies. From the analysis, it is found that sampling at 30 minutes gives the best forecast for daily volatility. The forecasting ability of these models is deteriorated, however, by the non‐normal property of mean adjusted returns, which is an assumption in conditional variance models. Nevertheless, the optimum frequency remained the same even in the case of different models (EGARCH and PARCH) and different error distribution (generalized error distribution, GED) where the error is reduced to a certain extent by incorporating the asymmetric effect on volatility. Our analysis also suggests that GARCH models with GED innovations or EGRACH and PARCH models would give better estimates of volatility with lower forecast error estimates. Copyright © 2008 John Wiley & Sons, Ltd.
Are all crowds equally wise? a comparison of political election forecasts by experts and the public
Authors: Sjöberg Lennart
Published: September 2008

Four groups made forecasts of the outcome of the Swedish Parliamentary election in the fall of 2006. They consisted of members of the public, political scientists, journalists writing about domestic politics in Swedish daily newspapers, and journalists who were editing sections of readers' letters in daily newspapers. They estimated, using a 12‐step category scale, which percentage of the votes that they believed seven parties would get in the election. Data were then obtained on the outcome of the election, and on the two opinions polls closest in time to it. When median forecasts were compared across groups, it was found that the group from the public was most successful in forecasting the outcome of the election. This was in spite of the fact that the median error made by individual members of that group was about 50% larger than the median error made by members of other groups. The two polls were less efficient than the group from the public and overestimated the span between the incumbent government and the opposition by a factor of 2. The members of the public and journalists showed some wishful thinking in their forecasts. There were large and consistent individual differences in forecasting ability. Men performed better than women, as did those who expressed more interest and knowledge in politics. Copyright © 2008 John Wiley & Sons, Ltd.
Agitation in the morning: symptom of depression in dementia?
Authors: Theison Anna‐Katharina , Geisthoff Urban W. , Förstl Hans , Schröder Stefan G.
Published: September 2008

Objective

To investigate the possible correlations between depression in dementia and agitation in the morning by a prospective naturalistic study.

Methods

Data were collected from three independent nursing homes in an urban setting. Trained nursing home staff pre‐selected 110 demented and agitated patients with a minimum age of 60 years. Three main groups were formed based on agitation peak either: in the morning, evening or none. Each is respectively: ‘sunrisers’, ‘sundowners’ and ‘constants’. Agitation was assessed by the same staff twice a day for a 2‐week timeframe using the CMAI (Cohen‐Mansfield Agitation Inventory); MMSE (Mini‐Mental State Examination) for dementia re‐evaluation and staging; CSDD (Cornell Score for Depression in Dementia) for depression screening.

Results

Sixty‐three (60%) of all patients were depressive but only 16 patients of them were treated with antidepressants. Forty‐four patients were classified as belonging to the ‘sunriser’ group, 38 to the ‘sundowners’ and 23 to the ‘constants’. There were no significant differences in depression between the three groups: p = 0.798 for the difference in proportion of depressed or not depressed people; p = 0.272 for the difference in raw Cornell‐score between agitation in the morning and evening.

Conclusion

‘Sunrising’ appears to play an important role in dementia. In our population agitation was slightly more common in the morning than in the evening, but peak of agitation does not seem to be related to depression in dementia. Our data supports that the diagnosis of depression is still often overlooked in demented and agitated persons. Copyright © 2008 John Wiley & Sons, Ltd.
Subjective health‐related quality of life of Chinese older persons with depression in Shanghai and Hong Kong: relationship to clinical factors, level of functioning and social support
Authors: Chan Sally , Jia Shoumei , Chiu Helen , Chien Wai‐Tong , R. Thompson David , Hu Yan , Lam Linda
Published: September 2008

Aim

This study aimed to measure and compare the perceptions of HRQoL amongst Chinese older people with depression between Hong Kong and Shanghai and to explore the association of HRQoL with clinical factors, level of functioning and social support in the two sites.

Methods and Results

A cross‐sectional study was conducted with a convenience sample of 80 older people from Hong Kong and 71 from Shanghai with a diagnosis of depression. The results showed that both the Hong Kong and Shanghai groups had a poor perception of their HRQoL when compared with Caucasian populations. The Shanghai group had a significantly higher HRQoL perception than did the Hong Kong group. Physical health problems that affected functional abilities also influenced older people's satisfaction with life. The severity of depression, number of medical conditions, functional abilities and satisfaction towards social support were predictors of HRQoL.

Conclusion

The high rate of depression in Hong Kong and Shanghai deserves attention. Older people with depression have both psychological and physical health care needs. This study provides insights for healthcare professionals to plan innovative and co‐ordinated services that meet the various health care needs of older people with depression. Copyright © 2008 John Wiley & Sons, Ltd.
The influence of economic incentives on reported disability status
Authors: Gannon Brenda
Published: September 2008

Self‐reported disability status is often relied upon in labour force participation models, but this may be reported with error for economic or psychological reasons and can lead to a bias in the effect of disability on participation. In this paper, we explore the possibility that reported limitations in daily activities are mis‐reported, in particular for those who define their labour force status as disabled/ill, and assess if economic incentives influence this group to mis‐report. The main questions we wish to address therefore are: (1) was there state‐dependent reporting error and did economic incentives play a role, and (2) did this change over the years 1995–2001? Using a generalised ordered response model, we compute cleansed measures of disability that correspond to predicted responses individuals would have made if employed. Unobserved differences between the employed and non‐employed may exist; therefore, we control for this via correlated random effects. The results indicate that the disabled/ill group did over‐report and the difference between actual and predicted probabilities only marginally changed between 1995 and 2001. The extent of this measurement error is lower once we control for unobserved heterogeneity. Copyright © 2008 John Wiley & Sons, Ltd.
Transcriptional profiling identifies an interferon‐associated host immune response in invasive squamous cell carcinoma of the skin
Authors: Wenzel Joerg , Tomiuk Stefan , Zahn Sabine , Küsters Daniel , Vahsen Anja , Wiechert Andreas , Mikus Sandra , Birth Michael , Scheler Marina , von Bubnoff Dagmar , Baron Jens M. , Merk Hans F. , Mauch Cornelia , Krieg Thomas , Bieber Thomas , Bosio Andreas , Hofmann Kay , Tüting Thomas , Peters Bettina
Published: September 2008

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)‐regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN‐regulated genes correlated with the extent of the lesional immune‐cell infiltrate. Immunohistological examinations confirmed the expression of IFN‐regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN‐regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN‐associated host responses play an important role in tumor immunosurveillance in the skin. © 2008 Wiley‐Liss, Inc.
Risk of prostate, breast and colorectal cancer after skin cancer diagnosis
Authors: Levi Fabio , Randimbison Lalao , Te Van‐Cong , Conconi Manuela Maspoli , La Vecchia Carlo
Published: September 2008

Ultraviolet radiation is the major cause of skin cancer, but promotes vitamin D synthesis, and vitamin D has been inversely related to the risk of several common cancers including prostate, breast and colorectum. We therefore computed the incidence of prostate, breast and colorectal cancer following skin cancer using the datasets of the Swiss cancer Registries of Vaud and Neuchâtel. Between 1974 and 2005, 6,985 histologically confirmed squamous cell skin cancers, 21,046 basal cell carcinomas and 3,346 cutaneous malignant melanomas were registered, and followed up to the end of 2005 for the occurrence of second primary cancer of the prostate, breast and colorectum. Overall, 680 prostate cancers were observed versus 568.3 expected (standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI): 1.11–1.29), 440 breast cancers were observed versus 371.5 expected (SIR = 1.18; 95% CI: 1.08–1.30) and 535 colorectal cancers were observed versus 464.6 expected (SIR = 1.15; 95% CI: 1.06–1.25). When basal cell, squamous cell and skin melanoma were considered separately, all the SIRs for prostate, breast and colorectal cancers were around or slightly above unity. Likewise, the results were consistent across strata of age at skin cancer diagnosis and location (head and neck versus others), and for male and female colorectal cancers. These findings, based on a population with a long tradition of systematic histologic examination of all surgically treated skin lesions, do not support the hypothesis that prostate, breast and colorectal cancer risk is decreased following skin cancer. © 2008 Wiley‐Liss, Inc.
HLA‐A2‐restricted CTL epitopes of a novel lung cancer‐associated cancer testis antigen, cell division cycle associated 1, can induce tumor‐reactive CTL
Authors: Harao Michiko , Hirata Shinya , Irie Atsushi , Senju Satoru , Nakatsura Tetsuya , Komori Hiroyuki , Ikuta Yoshiaki , Yokomine Kazunori , Imai Katsunori , Inoue Mitsuhiro , Harada Kumiko , Mori Takeshi , Tsunoda Takuya , Nakatsuru Shuichi , Daigo Yataro , Nomori Hiroaki , Nakamura Yusuke , Baba Hideo , Nishimura Yasuharu
Published: September 2008

Toward the development of a novel cancer immunotherapy, we have previously identified several tumor‐associated antigens (TAAs) and the epitopes recognized by human histocompatibility leukocyte (HLA)‐A2/A24‐restricted cytotoxic T lymphocyte (CTL). In this study, we tried to identify a TAA of lung cancer (LC) and its HLA‐A2 restricted CTL epitopes to provide a target antigen useful for cancer immunotherapy of LC. We identified a novel cancer testis antigen, cell division cycle associated gene 1 (CDCA1), overexpressed in nonsmall cell LC using a cDNA microarray analysis. The expression levels of CDCA1 were also increased in the majority of small cell LC, cholangiocellular cancer, urinary bladder cancer and renal cell cancers. We used HLA‐A2.1 transgenic mice to identify the HLA‐A2 (A*0201)‐restricted CDCA1 epitopes recognized by mouse CTL, and we investigated whether these peptides could induce CDCA1‐reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA‐A2‐positive donors and a NSCLC patient. Consequently, we found that the CDCA165–73 (YMMPVNSEV) peptide and CDCA1351–359 (KLATAQFKI) peptide could induce peptide‐reactive CTLs in HLA‐A2.1 transgenic mice. In HLA‐A2+ donors, in vitro stimulation of PBMC with these peptides could induce peptide‐reactive CTLs which killed tumor cell lines endogenously expressing both HLA‐A2 and CDCA1. As a result, CDCA1 is a novel cancer‐testis antigen overexpressed in LC, cholangiocellular cancer, urinary bladder cancer and renal cell cancers, and CDCA1 may therefore be an ideal TAA useful for the diagnosis and immunotherapy of these cancers. © 2008 Wiley‐Liss, Inc.
Effects of irrigation frequency under limited irrigation on root water uptake, yield and water use efficiency of winter wheat
Authors: Shao Liwei , Zhang Xiying , Chen Suying , Sun Hongyong , Wang Zhenhua
Published: September 2008

In the North China Plain, grain yield, water use efficiency (WUE) and root water uptake of winter wheat (Triticum aestivumL.) were investigated for five seasons, under different irrigation frequencies associated with limited water supply. Results showed that, with half of the normal irrigation amount, the combination of different irrigation amounts per application and the total number of irrigation applications did not affect grain production and WUE in most of the seasons during 2002–07. Due to the high soil water‐holding capacity and large root system of winter wheat, crop water use during each season was similar for all treatments. Results suggest that deficit irrigation applications given to crops in several small amounts were no better than applying them in relatively large quantities, typically as two or even one application. Good soil moisture conditions at sowing also played an important role in achieving high yields of this crop under limited water supply. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of size at the nanoscale and bilayer rigidity on skin diffusion of liposomes
Authors: Babu Sundar , Fan Chenxiang , Stepanskiy Leonard , Uitto Jouni , Papazoglou Elisabeth
Published: September 2008

This study reports the effect of liposome particle size at the nanoscale and bilayer deformability on the permeation through MatTek human skin equivalents and provides a comparative quantitative measure through calculation of diffusion coefficients. Exploring DOPC and DPPC fluorescent liposomes, our results demonstrate the faster diffusion of 50 nm liposomes compared with 100 and 200 nm liposomes when the lipid bilayer remains the same. Diffusion kinetics of the 50 nm particles appear not to depend on the rigidity of the lipid layer, whereas diffusion of particles larger than 100 nm is significantly affected by the rigidity of the bilayer, and DOPC liposomes diffuse faster than their DDPC equivalents. Our results suggest that liposomes composed of a rigid bilayer can be expected to remain intact after passing through the stratum corneum. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009