bluuebunny/crossref_metadata_2025 huggingface dataset:
Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection
Authors: Hirai Toshiro , Yoshikawa Tomoaki , Nabeshi Hiromi , Yoshida Tokuyuki , Tochigi Saeko , Ichihashi Ko-ichi , Uji Miyuki , Akase Takanori , Nagano Kazuya , Abe Yasuhiro , Kamada Haruhiko , Itoh Norio , Tsunoda Shin-ichi , Yoshioka Yasuo , Tsutsumi Yasuo
Published: February 2012

Background

Due to the rising use of nanomaterials (NMs), there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs), which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis.

Results

We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigenDermatophagoides pteronyssinus(Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions.

Conclusions

A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.
Rapid synaptic potentiation within the anterior cingulate cortex mediates trace fear learning
Authors: Descalzi Giannina , Li Xiang-Yao , Chen Tao , Mercaldo Valentina , Koga Kohei , Zhuo Min
Published: February 2012

Although the cortex has been extensively studied in long-term memory storage, less emphasis has been placed on immediate cortical contributions to fear memory formation. AMPA receptor plasticity is strongly implicated in learning and memory, and studies have identified calcium permeable AMPA receptors (CP-AMPARs) as mediators of synaptic strengthening. Trace fear learning engages the anterior cingulate cortex (ACC), but whether plastic events occur within the ACC in response to trace fear learning, and whether GluN2B subunits are required remains unknown. Here we show that the ACC is necessary for trace fear learning, and shows a rapid 20% upregulation of membrane AMPA receptor GluA1 subunits that is evident immediately after conditioning. Inhibition of NMDA receptor GluN2B subunits during training prevented the upregulation, and disrupted trace fear memory retrieval 48 h later. Furthermore, intra-ACC injections of the CP-AMPAR channel antagonist, 1-naphthylacetyl spermine (NASPM) immediately following trace fear conditioning blocked 24 h fear memory retrieval. Accordingly, whole cell patch clamp recordings from c-fos positive and c-fos negative neurons within the ACC in response to trace fear learning revealed an increased sensitivity to NASPM in recently activated neurons that was reversed by reconsolidation update extinction. Our results suggest that trace fear learning is mediated through rapid GluN2B dependent trafficking of CP-AMPARs, and present in vivo evidence that CP-AMPAR activity within the ACC immediately after conditioning is necessary for subsequent memory consolidation processes.
Focal adhesion kinase contributes to proliferative potential of ErbB2 mammary tumour cells but is dispensable for ErbB2 mammary tumour induction in vivo
Authors: Lahlou Hicham , Sanguin-Gendreau Virginie , Frame Margaret C , Muller William J
Published: February 2012

Introduction

Activation of focal adhesion kinase (FAK) is hypothesized to play an important role in the pathogenesis of human breast cancer.

Methods

To directly evaluate the role of FAK in mammary tumour progression, we have used a conditional FAK mouse model and mouse mammary tumour virus (MMTV)-driven Cre recombinase strain to inactivate FAK in the mammary epithelium of a transgenic mouse model of ErbB2 breast cancer.

Results

Although mammary epithelial disruption of FAK in this model resulted in both a delay in onset and a decrease in the number of neoplastic lesions, mammary tumours occurred in 100% of virgin female mice. All of the tumours and derived metastases that developed were proficient for FAK due to the absence of Cre recombinase expression. The hyperplastic epithelia where Cre-mediated recombination of FAK could be detected exhibited a profound proliferative defect. Consistent with these observations, disruption of FAK in established tumour cells resulted in reduced tumour growth that was associated with impaired proliferation. To avoid the selection for FAK-proficient ErbB2 tumour epithelia through escape of Cre-mediated recombination, we next intercrossed the FAK conditional mice with a separate MMTV-driven ErbB2 strain that co-expressed ErbB2 and Cre recombinase on the same transcriptional unit.

Conclusions

While a delay in tumour induction was noted, FAK-deficient tumours arose in 100% of female animals indicating that FAK is dispensable for ErbB2 tumour initiation. In addition, the FAK-null ErbB2 tumours retained their metastatic potential. We further demonstrated that the FAK-related Pyk2 kinase is still expressed in these tumours and is associated with its downstream regulator p130Cas. These observations indicate that Pyk2 can functionally substitute for FAK in ErbB2 mammary tumour progression.
Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes
Authors: Lipshultz Steven E. , Miller Tracie L. , Scully Rebecca E. , Lipsitz Stuart R. , Rifai Nader , Silverman Lewis B. , Colan Steven D. , Neuberg Donna S. , Dahlberg Suzanne E. , Henkel Jacqueline M. , Asselin Barbara L. , Athale Uma H. , Clavell Luis A. , Laverdière Caroline , Michon Bruno , Schorin Marshall A. , Sallan Stephen E.
Published: February 2012

Purpose

Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy.

Patients and Methods

Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment.

Results

cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables.

Conclusion

cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.
First-SIGNAL: First-Line Single-Agent Iressa Versus Gemcitabine and Cisplatin Trial in Never-Smokers With Adenocarcinoma of the Lung
Authors: Han Ji-Youn , Park Keunchil , Kim Sang-We , Lee Dae Ho , Kim Hyae Young , Kim Heung Tae , Ahn Myung Ju , Yun Tak , Ahn Jin Seok , Suh Cheolwon , Lee Jung-Shin , Yoon Sung Jin , Han Jong Hee , Lee Jae Won , Jo Sook Jung , Lee Jin Soo
Published: February 2012

Purpose

Gefitinib has shown high response rate and improved progression-free survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy.

Patients and Methods

In this randomized phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ function were randomly assigned to receive either gefitinib (250 mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m2on days 1 and 8; cisplatin 80 mg/m2on day 1 every 3 weeks, for up to nine courses). The primary objective was to demonstrate better overall survival (OS) for gefitinib compared with GP in chemotherapy-naive NSLAs.

Results

Three hundred nine patients were analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to 1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to 1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101). Myelosuppression, renal insufficiency, and fatigue were more common in the GP arm, but skin toxicities and liver dysfunction were more common in the gefitinib arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease and died.

Conclusion

Gefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.
Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987
Authors: Bellmunt Joaquim , von der Maase Hans , Mead Graham M. , Skoneczna Iwona , De Santis Maria , Daugaard Gedske , Boehle Andreas , Chevreau Christine , Paz-Ares Luis , Laufman Leslie R. , Winquist Eric , Raghavan Derek , Marreaud Sandrine , Collette Sandra , Sylvester Richard , de Wit Ronald
Published: February 2012

Purpose

The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival.

Patients and Methods

We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity.

Results

From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001).

Conclusion

The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.
System Dynamics Transforms Fluor Project and Change Management
Authors: Godlewski Edward , Lee Gregory , Cooper Kenneth
Published: February 2012

Fluor Corporation designs and builds many of the world's most complex projects and serves clients in many industries across six continents. On our most complex projects, we have implemented a system dynamics model-based system that has improved our project management, transformed our change management, and brought large quantified business benefits to us and our clients. The model can be rapidly set up and tailored to each major engineering and construction project. We use it to foresee the future cost and schedule impacts of project changes, and most important, to test ways to avoid the impacts. Since 2005, Fluor has used the system on over 100 projects and has trained hundreds of project managers and planners in its ongoing internal use. Quantitative business benefits exceed $800 million to date for Fluor and our clients. It has also transformed the mindset of our managers away from the industry's typical retrospective view, in which disputes could become the channel for resolving cost responsibility, and replaced it with a proactive approach, in which we work with our clients to find, in advance, ways to mitigate impacts and reduce costs—a win-win situation for Fluor and our clients.
Book Reviews
Authors: Rand Graham K.
Published: February 2012

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an e-mail from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor.

The following books are reviewed in this issue of Interfaces, 42(1), January–February 2012: Profiles in Operations Research: Pioneers and Innovators, Arjang A. Assad and Saul I. Gass, eds.; Operations Rules: Delivering Customer Value through Flexible Operations, David Simchi-Levi; Service Parts Management: Demand Forecasting and Inventory Control, Nezih Altay and Lewis A. Litteral, eds.; Linear Programming Sensitivity Analysis and Related Topics, Marie-France Derhy; Artificial Ants: From Collective Intelligence to Real-life Optimization and Beyond, Nicolas Monmarche, Frederic Guinand, and Patrick Siarry, eds.
Tax Collections Optimization for New York State
Authors: Miller Gerard , Weatherwax Melissa , Gardinier Timothy , Abe Naoki , Melville Prem , Pendus Cezar , Jensen David , Reddy Chandan K. , Thomas Vince , Bennett James , Anderson Gary , Cooley Brent
Published: February 2012

The New York State Department of Taxation and Finance (NYS DTF) collects over $1 billion annually in assessed delinquent taxes. The mission of DTF's Collections and Civil Enforcement Division (CCED) is to increase collections, but to do so in a manner that respects the rights of citizens, by taking actions commensurate with each debtor's situation. CCED must accomplish this in an environment with limited resources. In a collaborative work, NYS DTF, IBM Research, and IBM Global Business Services developed a novel tax collection optimization solution to address this challenge. The operations research-based solution combines data analytics and optimization using the unifying framework of constrained Markov decision processes (C-MDP). The system optimizes the collection actions of agents with respect to maximizing long-term returns, while taking into account the complex dependencies among business needs, resources, and legal constraints. It generates a customized collections policy instead of broad-brush rules, thereby improving both the efficiency and adaptiveness of the collections process. It also enhances and improves the tax agency's ability to administer taxes equitably across the broad scope of individual taxpayers' situations. The system became operational in December 2009; from 2009 to 2010, New York State increased its collections from delinquent revenue by $83 million (8 percent) using the same set of resources. Given a typical annual increase of 2 to 4 percent, the system's expected benefit is approximately $120 to $150 million over a period of three years, far exceeding the initial target of $90 million.
Spiroketals: Toward the synthesis of 39-oxobistramide K
Authors: Commandeur Malgorzata , Commandeur Claude , Cossy Janine
Published: February 2012

An advanced spiroketal intermediate toward the synthesis of 39-oxobistramide K was prepared, fragment C14–C40. This fragment was obtained in 19 steps with an overall yield of 6.2 % using a FeCl3-catalyzed spiroketalization as the key step.
Closing the Gaps in Pediatric Laboratory Reference Intervals: A CALIPER Database of 40 Biochemical Markers in a Healthy and Multiethnic Population of Children
Authors: Colantonio David A , Kyriakopoulou Lianna , Chan Man Khun , Daly Caitlin H , Brinc Davor , Venner Allison A , Pasic Maria D , Armbruster David , Adeli Khosrow
Published: February 2012

BACKGROUND

Pediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population.

METHODS

Healthy children and adolescents (n = 2188, newborn to 18 years of age) were recruited from a multiethnic population with informed parental consent and were assessed from completed questionnaires and according to defined exclusion criteria. Whole-blood samples were collected for establishing age- and sex-stratified reference intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids, proteins) on the Abbott ARCHITECT c8000 analyzer.

RESULTS

Reference intervals were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East Asians, and South Asian participants were evaluated with respect to the influence of ethnicity, and statistically significant differences were observed for 7 specific biomarkers.

CONCLUSIONS

The establishment of a new comprehensive database of pediatric reference intervals is part of the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER). It should assist laboratorians and pediatricians in interpreting test results more accurately and thereby lead to improved diagnosis of childhood diseases and reduced patient risk. The database will also be of global benefit once reference intervals are validated in transference studies with other analytical platforms and local populations, as recommended by the CLSI.
Toward a Political Theory of Criminal Law
Authors: Melissaris Emmanuel
Published: February 2012

The aim of this paper is to outline a political theory of criminal law, that is, a theory that does not rely on any controversial moral view on fault and punishment. The argument is based largely on John Rawls's work but also addresses some inconsistencies regarding crime and punishment therein. The paper will make a case for a mixed theory of criminal law and punishment along the following lines: The fair terms of social cooperation generate duties for the violation of which one can be held properly responsible. However, nothing in this determines what the accountability-seeking measure may be or its intensity. These are matters of appropriateness to be determined in terms of the assurance of the participants in a well-ordered society and the long-term stability of social cooperation. Criminalization and punishment are contingent, historically qualified means of achieving stability and assurance, serving only as last resort. Although the institution of punishment is subject to the constraints of the rule of law, which stem directly from the liberty principle, questions such as the intensity of punishment or the proportionality between offenses and penalties depend on the proper workings of the utilitarian calculus in combination with the requirements of democratic decision-making.
Functional Difficulties and Health Conditions Among Children With Special Health Needs
Authors: Lollar Donald J. , Hartzell Marilyn Sue , Evans Mary Ann
Published: February 2012

OBJECTIVES:

To describe the functional difficulties of children with special health needs and to demonstrate the shared and unique contributions in predicting health outcomes and informing therapeutic interventions, policies, and research by using data from the 2005–2006 National Survey of Children With Special Health Care Needs.

RESULTS:

Children with special health care needs experience an array of health conditions and functional difficulties that are interrelated. Although health conditions tend not to change, the characteristics of functional difficulties are subject to changes over time with age or as a result of interventions. Descriptive data highlight common functional difficulties across health conditions. Multiple regression analyses support both health conditions and functional difficulties predicting (1) health services, such as emergency department visits, (2) personal limitations such as impairment of daily activities and school absences, and (3) family impact, stopping or reducing work. Functional difficulties were, however, the stronger predictor for all outcomes except school absences.

CONCLUSIONS:

The results support the utility of expanding measures of children with special health care needs to include functional difficulties in survey research, as well as clinical and public health practice. Systematic inclusion of functional difficulties will inform policy development, program planning, outcome assessment, and resource allocation for this vulnerable population. A focus on functional difficulties facilitates stronger coordination of services across sectors including physical health, mental health, education, and other social services to improve the health and well-being for these children and youth.
What the Orphan Drug Act Has Done Lately for Children With Rare Diseases: A 10-Year Analysis
Authors: Thorat Chandana , Xu Kui , Freeman Scott N. , Bonnel Renan A. , Joseph Francesca , Phillips M. Ian , Imoisili Menfo A.
Published: February 2012

OBJECTIVES:

The 1983 US Orphan Drug Act (ODA) provided incentives to stimulate treatment product development for patients with rare disease. This article highlights a decade of ODA contributions to this goal for children with RDs.

METHODS:

An internal US Food and Drug Administration database was the information source for orphan designations, marketing approvals, and prevalence numbers for 2000 to 2009. Product categorization was based on the disease age of onset for which they received designation. Category 1 products were for diseases with onset exclusively in Childhood; Category 2 products were for diseases with onset at any age; and Category 3 products were for diseases with adult onset only. Disease prevalence distributions were analyzed by using population intervals of 20 000.

RESULTS:

From 2000 to 2009, 1138 orphan drugs were designated and 148 received marketing approval, of which 38 (26%) were for pediatric diseases. The proportion of approvals for pediatric products increased from 17.5% (10 of 57) in the first half of the decade, to 30.8% (28 of 91) in the second. More products received designation and marketing approval for pediatric diseases with prevalence numbers fewer than 20 000 than for any other prevalence subgroup. The median disease prevalence for all pediatric orphan designations that received marketing approval was 8972. Among the pediatric orphan drug approvals categorized by therapeutic class, the endocrine/metabolic drugs had the largest representation (39%).

CONCLUSIONS:

The ODA incentives have led to increased product availability for RDs overall, with an increasing number of marketing approvals for children this past decade.
Self-Referral and Serious Illness in Children With Fever
Authors: van Ierland Yvette , Seiger Nienke , van Veen Mirjam , van Meurs Alfred H. J. , Ruige Madelon , Oostenbrink Rianne , Moll Henriëtte A.
Published: February 2012

OBJECTIVE:

The goal of this study was to evaluate parents’ capability to assess their febrile child’s severity of illness and decision to present to the emergency department. We compared children referred by a general practitioner (GP) with those self-referred on the basis of illness-severity markers.

METHODS:

This was a cross-sectional observational study conducted at the emergency departments of a university and a teaching hospital. GP-referred or self-referred children with fever (aged <16 years) who presented to the emergency department (2006–2008) were included. Markers for severity of illness were urgency according to the Manchester Triage System, diagnostic interventions, therapeutic interventions, and follow-up. Associations between markers and referral type were assessed by using logistic regression analysis. Subgroup analyses were performed for patients with the most common presenting problems that accompanied the fever (ie, dyspnea, gastrointestinal complaints, neurologic symptoms, fever without specific symptoms).

RESULTS:

Thirty-eight percent of 4609 children were referred by their GP and 62% were self-referred. GP-referred children were classified as high urgency (immediate/very urgent categories) in 46% of the cases and self-referrals in 45%. Forty-three percent of GP referrals versus 27% of self-referrals needed extensive diagnostic intervention, intravenous medication/aerosol treatment, hospitalization, or a combination of these (odds ratio: 2.0 [95% confidence interval: 1.75–2.27]). In all subgroups, high urgency was not associated with referral type. GP-referred and self-referred children with dyspnea had similar frequencies of illness-severity markers.

CONCLUSIONS:

Although febrile self-referred children were less severely ill than GP-referred children, many parents properly judged and acted on the severity of their child’s illness. To avoid delayed or missed diagnoses, recommendations regarding interventions that would discourage self-referral to the emergency department should be reconsidered.
Clinical factors determining the efficacy of urinary bladder tumour treatments in dogs: Surgery, chemotherapy or both?
Authors: Molnár Tamás , Vajdovich Péter
Published: February 2012

In a study of 44 canine patients suffering from histopathologically proven urinary bladder tumour with a high incidence of transitional cell carcinoma (TCC) (n = 35), a close relationship was found either between the disease-free period and the age (r = −0.40) of animals or between the survival times and the age (r = −0.62) of animals after treatment. In addition to the dog breeds known to be prone to have urinary bladder tumour, we found an additional potentially sensitive breed, the Hungarian Vizsla. The median survival times obtained by the applied treatment types were as follow: ‘surgery and chemotherapy’ (n = 8/44) 475 days, ‘surgery alone’ (n = 19/44) 240 days, ‘chemotherapy alone’ (n = 7/44) 31 days, and ‘no treatment’ (n = 10/44) 7 days (P < 0.001). According to the findings, chemotherapy combined with surgery completed in time is the most effective protocol in the treatment of urinary bladder tumour cases in dogs. A rational and more effective procedure for the assessment and treatment of urinary bladder tumour cases is presented.
The pharmacological treatment of obesity: Past, present and future
Authors: Simonyi Gábor , Pados Gyula , Medvegy Mihály , Bedros J. Róbert
Published: February 2012

Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one. Orv. Hetil., 2012, 153, 363–373.
Effect of Microalloying Elements (B, Nb, V and Ti) on the Strain Hardening Behavior of High-Manganese TWIP Steels.
Authors: Reyes-Calderón F. , Mejía I. , Cabrera J.M.
Published: February 2012

The present research work analyses the influence of microalloying elements (B, Nb, V and Ti) on the tensile strength and the strain hardening behavior of a high-manganese TWIP steel. The analysis was carried out by means of true stress-true strain curves derived from uniaxial tension tests. The work hardening exponent was determined by using the Hollomon and differential Crussard-Jaoul models. Metallographic characterization was carried out to determine the metallurgical changes associated with n values. The results indicate that the Hollomon analysis results in strain hardening exponent values up to 0.46. On the other hand, the differential Crussard-Jaoul analysis establishes a clear distinction of n value for two stages of plastic deformation which are determined by a sharp slope change in the plot of ln(dσ/dε)-lnε.
Using phylogenetic trees to test for character displacement: a model and an example from a desert mammal community
Authors: Davies T. Jonathan , Cooper Natalie , Diniz-Filho Jose Alexandre Felizola , Thomas Gavin H. , Meiri Shai
Published: February 2012

The distribution of traits within communities is thought to provide information on the evolutionary and ecological forces that structure community composition. Ecological character displacement (evolutionary divergence among populations of interacting species within a community), as well as community‐wide character displacement (even dispersion of species traits within a community via species sorting), have been widely reported and are typically interpreted as evidence for interspecific competition. However, defining an appropriate null distribution with which to assess the observed distribution of traits within a community has proved controversial. Phylogenetic methods provide an alternative approach to evaluating community structure, but such methods also require an appropriate null and have typically overlooked the potential for evolutionary dynamics within communities. Here, we present a novel phylogenetic framework that uses evolutionary expectations to generate a simple null model of the expected distribution of traits among co‐occurring species. Using a stochastic Brownian motion model of trait change, we illustrate that the expected community‐wide dispersion of traits varies with phylogenetic tree shape. We then use data on body mass for mammals to evaluate the accuracy with which phylogeny can predict the empirical distribution of traits and find a strong correlation between predicted and observed trait distributions. We suggest that deviations from phylogenetic expectations may therefore provide a useful tool for evaluating the role of competition in shaping community structure. Finally, we demonstrate the utility of our approach using empirical data on body mass and a phylogeny for a small community of terrestrial mammals in Yotvata, Israel, and reveal evidence consistent with ecological and community‐wide character displacement. Our method unites ecological and evolutionary approaches, and it provides a novel framework for exploring community structure.
Assessing the effects of spatial contingency and environmental filtering on metacommunity phylogenetics
Authors: Peres-Neto Pedro R. , Leibold Mathew A. , Dray Stéphane
Published: February 2012

Patterns in biodiversity and species coexistence are the result of multiple interacting processes including evolutionary history, trait variation, species interactions, dispersal, environmental variation, and landscape heterogeneity. Exploring patterns of biodiversity across space is perhaps the best integrative method (in contrast to the scarcity of temporal data) to interpret the influence of these multiple and interactive effects in determining community assembly, but it is still underdeveloped. Two emerging fields, metacommunity ecology and community phylogenetics, have been making relevant, though rather independent, progress toward understanding how communities are assembled in space. Our main goals were twofold. First, we described a heuristical framework to merge these two fields into “metacommunity phylogenetics.” The main goal of this framework is to provide a way to think about how niche properties of species arranged across the environment and different spatial scales influence the process of community assembly. Second, we developed an analytical framework to link niche properties based on trait and phylogenetics to environmental and spatial variation. In order to assess the performance of the framework, we used extensive computer simulations of community assembly to show that the procedure is robust under a variety of scenarios.
Principles of Hand Fracture Management
Authors: Haughton DN , Jordan D , Malahias M , Hindocha S , Khan W
Published: February 2012

The hand is essential in humans for physical manipulation of their surrounding environment. Allowing the ability to grasp, and differentiated from other animals by an opposing thumb, the main functions include both fine and gross motor skills as well as being a key tool for sensing and understanding the immediate surroundings of their owner.

Hand fractures are the most common fractures presenting at both accident and emergency and within orthopaedic clinics. Appropriate evaluation at first presentation, as well as during their management, can significantly prevent both morbidity and disability to a patient. These decisions are dependant on a wide range of factors including age, hand dominance, occupation and co-morbidities.

A fracture is best described as a soft tissue injury with an associated bony injury. Despite this being the case, this paper intends to deal mainly with the bone injury and aims to discuss both the timing, as well as the methods available, of hand fracture management.
Recent Surgical and Medical Advances in the Treatment of Dupuytren’s Disease - A Systematic Review of the Literature
Authors: R Mafi , S Hindocha , W Khan
Published: February 2012

Dupuytren’s disease (DD) is a type of fibromatosis which progressively results in the shortening and thickening of the fibrous tissue of the palmar fascia. This condition which predominantly affects white-northern Europeans has been identified since 1614. DD can affect certain activities of daily living such as face washing, combing hair and putting hand in a glove. The origin of Dupuytren’s contracture is still unknown, but there are a number of treatments that doctors have come across throughout the years. Historically surgery has been the mainstay treatment for DD but not the only one. The objective is to make a structured review of the most recent advances in treatment of DD including the surgical and medical interventions. We have looked at the most relevant published articles regarding the various treatment options for DD. This review has taken 55 articles into consideration which have met the inclusion criteria. The most recent treatments used are multi-needle aponeurotomy, extensive percutaneous aponeurotomy and lipografting, injecting collagenase Clostridium histolyticum, INF-gamma and shockwave therapy as well as radiotherapy. Each of these treatments has certain advantages and drawbacks and cannot be used for every patient. In order to prevent this condition, spending more time and money in the topic is required to reach better and more consistent treatments and ultimately to eradicate this disease.
Immune Reconstitution During the First Year of Antiretroviral Therapy of HIV-1-Infected Adults in Rural Burkina Faso
Authors: Tiba Fabrice , Nauwelaers Frans , Traoré Siaka , Coulibaly Boubacar , Ouedraogo Thierry , Compaoré Adama , Kräusslich Hans-Georg , Böhler Thomas
Published: February 2012

There are no data on the outcome of highly active antiretroviral therapy (HAART) in HIV-infected adults in rural Burkina Faso. We therefore assessed CD4+T-cell counts and HIV-1 plasma viral load (VL), the proportion of naive T-cells (co-expressing CCR7 and CD45RA) and T-cell activation (expression of CD95 or CD38) in 61 previously untreated adult patients from Nouna, Burkina Faso, at baseline and 2 weeks, 1, 3, 6, 9 and 12 months after starting therapy. Median CD4+T-cell counts increased from 174 (10th-90thpercentile: 33-314) cells/µl at baseline to 300 (114- 505) cells/µl after 3 months and 360 (169-562) cells/µl after 12 months of HAART. Median VL decreased from 5.8 (4.6- 6.6) log10 copies/ml at baseline to 1.6 (1.6-2.3) log10 copies/ml after 12 months. Early CD4+T-cell recovery was accompanied by a reduction of the expression levels of CD95 and CD38 on T-cells. Out of 42 patients with complete virological follow-up under HAART, 19 (45%) achieved concordant good immunological (gain of ≥100 CD4+T-cells/µl above baseline) and virological (undetectable VL) responses after 12 months of treatment (intention-to-treat analysis). Neither a decreased expression of the T-cell activation markers CD38 and CD95, nor an increase in the percentage of naive T-cells reliably predicted good virological treatment responses in patients with good CD4+T-cell reconstitution. Repeated measurement of CD4+T-cell counts during HAART remains the most important parameter for immunologic monitoring. Substitution of repeated VL testing by determination of T-cell activation levels (e.g., CD38 expression on CD8+T-cells) should be applied with caution.
Reassessing the Clinical Significance of Chorionic Membrane Microcysts and Linear Necrosis
Authors: Bendon Robert W. , Coventry Susan C. , Reed Robyn C.
Published: February 2012

Recent studies have suggested that 2 lesions of the fetal membranes, linear necrosis at the choriodecidual junction and chorionic membrane microcysts, are markers of uteroplacental ischemia. To evaluate this hypothesis, we examined 807 placentas from unselected, consecutive deliveries at a single hospital over approximately 6 months with specific recording of the presence of chorionic microcysts or linear membrane necrosis. Clinical factors that might indicate uteroplacental ischemia were abstracted from the pathology report, including small for gestational age, pregnancy-induced hypertension, meconium macrophages in the membranes, infarctions, and small placenta. We found that both chorionic microcysts and linear membrane necrosis are very common lesions in unselected placentas, involving 28% and 18% of all placentas, respectively. There was no correlation between the presence of chorionic membrane microcysts and any marker of uteroplacental ischemia. Linear necrosis correlated only with the presence of meconium macrophages. We conclude that these membrane changes are not a useful marker of ischemia in an unselected population of placentas. We suggest caution in the interpretation of these findings, to avoid overdiagnosing ischemia or other pathologic processes.
A note on the extent of two subclasses of star countable spaces
Authors: Yu Zuoming
Published: February 2012

We prove that every Tychonoff strongly monotonically monolithic star countable space is Lindelöf, which solves a question posed by O.T. Alas et al. We also use this result to generalize a metrization theorem for strongly monotonically monolithic spaces. At the end of this paper, we study the extent of star countable spaces with k-in-countable bases, k ∈ ℤ.
Formation of dioxospiroindene[1,3]thiazine and thioxoindeno[2,1-d]imidazolone derivatives from alkenylidene-hydrazinecarbothioamides
Authors: Hassan Alaa , Nour El-Din Ahmed , Abdel-Latif Fathy , Mostafa Sara , Bräse Stefan
Published: February 2012

The reaction of (substituted) alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile led to the formation of 1,3-dioxospiroindene[1,3]-thiazine and thioxoindeno[2,1-d]imidazolone derivatives in modest yields. In addition, 1,3-dihydroxyindan-2-ylidenepropanedinitrile was found. Explanations of these conversions involving nucleophilic reactions and condensations are presented.
Oscillation of first-order differential equations with retarded arguments
Authors: Karpuz Başak
Published: February 2012

In this paper, we provide a test under which every solution of a first-order delay differential equation oscillates. An example is given to illustrate the significance of the result.
Some Tauberian conditions for Cesàro summability method
Authors: Çanak İbrahi̇m , Totur Ümi̇t
Published: February 2012

Let u = (u
n) be a sequence of real numbers whose generator sequence is Cesàro summable to a finite number. We prove that (u
n) is slowly oscillating if the sequence of Cesàro means of (ω
n(m−1)(u)) is increasing and the following two conditions are hold: $$\begin{gathered}
\left( {\lambda - 1} \right)\mathop {\lim \sup }\limits_n \left( {\frac{1}
{{\left[ {\lambda n} \right] - n}}\sum\limits_{k = n + 1}^{\left[ {\lambda n} \right]} {\left( {\omega _k^{\left( m \right)} \left( u \right)} \right)^q } } \right)^{\frac{1}
{q}} = o\left( 1 \right), \lambda \to 1^ + , q > 1, \hfill \\
\left( {1 - \lambda } \right)\mathop {\lim \sup }\limits_n \left( {\frac{1}
{{n - \left[ {\lambda n} \right]}}\sum\limits_{k = \left[ {\lambda n} \right] + 1}^n {\left( {\omega _k^{\left( m \right)} \left( u \right)} \right)^q } } \right)^{\frac{1}
{q}} = o\left( 1 \right), \lambda \to 1^ - , q > 1, \hfill \\
\end{gathered}$$ where (ω
n(m) (u)) is the general control modulo of the oscillatory behavior of integer order m ≥ 1 of a sequence (u
n) defined in [DİK, F.: Tauberian theorems for convergence and subsequential convergence with moderately oscillatory behavior, Math. Morav. 5, (2001), 19–56] and [λn] denotes the integer part of λn.
Some common fixed point theorems for hybrid pairs of maps without the completeness assumption
Authors: Imdad M. , Ahmed M.
Published: February 2012

Motivated by some recent works due to Singh and Kumar and Ahmed, the main result of Imdad and Ali is generalized and improved by removing the completeness assumption besides weakening the quasi-coincidentally commuting property of the involved hybrid pair to S-weak commutativity. Some illustrative examples are also furnished to support the genuineness of our extension besides deriving some related results.
On lightlike geometry in indefinite Kenmotsu manifolds
Authors: Massamba Fortuné
Published: February 2012

We investigate some geometric aspects of lightlike hypersurfaces of indefinite Kenmotsu manifolds, tangent to the structure vector field, by paying attention to the geometry of leaves of integrable distributions. Theorems on parallel vector fields, Killing distribution, geodesibility of their leaves are obtained. The geometric configuration of such lightlike hypersurfaces and leaves of its screen integrable distributions are established. We show that no totally contact umbilical leaf of a screen integrable distribution of a lightlike hypersurface can be an extrinsic sphere. We also prove that the geometry of any leaf of an integrable distribution is closely related to the geometry of a normal bundle.
Subcontinuity
Authors: Holá Ľubica , Novotný Branislav
Published: February 2012

We give interesting characterizations using subcontinuity. Let X, Y be topological spaces. We study subcontinuity of multifunctions from X to Y and its relations to local compactness, local total boundedness and upper semicontinuity. If Y is regular, then F is subcontinuous iff $$\bar F$$ is USCO. A uniform space Y is complete iff for every topological space X and for every net {F
a}, F
a ⊂ X × Y, of multifunctions subcontinuous at x ∈ X, uniformly convergent to F, F is subcontinuous at x. A Tychonoff space Y is Čech-complete (resp. G
m-space) iff for every topological space X and every multifunction F ⊂ X × Y the set of points of subcontinuity of F is a G
δ-subset (resp. G
m-subset) of X.
Reliability, Flexibility, and Environmental Impact of Alternative Objective Functions for Arterial Offset Optimization
Authors: Day Christopher M. , Brennan Thomas M. , Hainen Alexander M. , Remias Stephen M. , Premachandra Hiromal , Sturdevant James R. , Richards Greg , Wasson Jason S. , Bullock Darcy M.
Published: February 2012

A wide variety of alternative optimization objective functions, such as minimizing stops, minimizing delay, and maximizing arrivals on green, has been reported in the literature. An extensive literature evaluates these alternative objective functions with models. This paper reports on the field deployment of these alternative optimization functions, developed with high resolution controller data, to adjust offsets on an arterial system of eight coordinated signals. The deployment consisted of a 1-week base data collection and four 1-week deployments of offset plans developed with four alternative optimization objective functions. Travel times of anonymous probe vehicles were measured during the study period to evaluate the impact of these alternative optimization functions on corridor travel time. All objective functions were successful in reducing median corridor travel time significantly. Median travel time decreased by more than 1 min in both directions on the 5-mi corridor. Travel time reliability, as quantified by the difference between 75th and 25th percentile travel times, was improved for the busiest portion of the day. A lower bound of the estimated annual savings on user costs was $472,817, with an associated reduction in carbon dioxide emissions of 197 tons per year.