bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Culture of Human Bone Marrow Stromal Cells with Endothelial Cells Alters Gene Expression Profiles
Authors: Xue Ying , Xing Zhe , Bolstad Anne Isine , Van Dyke Thomas E. , Mustafa Kamal
Published: August 2013

The intricate relationship between angiogenesis and osteogenesis in vivo must be replicated in bone tissue engineering constructs to ensure the formation of a functional vascular network to support successful bone formation. Although communication between bone marrow stromal cells (MSC) and endothelial cells (EC) is recognized as one of the most important cellular interactions in bone regeneration, the underlying mechanisms of this biological process are not well understood. The purpose of this study was to analyze global gene expression associated with intercellular communication between MSC and EC using HumanWG-6 v3.0 expression BeadChips with a one-channel platform system (Illumina, San Diego, CA, USA). Each array contains more than 48,000 probes derived from human genes. A global map of MSC gene expression was generated following co-culture of MSC with EC for 5 and 15 days, in a direct-contact model. The map was used to determine relative alterations in functional processes and pathways. Co-culturing EC with MSC up-regulated genes related to angiogenesis as von Willebrand factor, platelet/endothelial cell adhesion molecule-1, cadherin 5, angiopoietin-related protein 4, and cell surface antigen CD34, and genes playing important roles in osteogenesis as alkaline phosphatase, FK506 binding protein 5, and bone morphogenetic protein. These findings clearly demonstrated that EC had a significant impact on MSC, particularly the bidirectional regulation of angiogenesis and osteogenesis. Moreover, cell-matrix interactions and TGF-β signal pathways were implicated for a crucial role in endothelial, cell-induced gene regulation in MSCs. A detailed study of the functional correlates of the microarray data is warranted to explore cellular and molecular interactions of importance in bone tissue engineering.
Fixation and Mounting of Porcine Aortic Valves for use in Mock Circuits
Authors: Schlöglhofer Thomas , Aigner Philipp , Stoiber Martin , Schima Heinrich
Published: August 2013

Purpose

Investigations of the circulatory system in vitro use mock circuits that require valves to mimic the cardiac situation. Whereas mechanical valves increase water hammer effects due to inherent stiffness and do not allow the use of pressure lines or catheters, bioprosthetic valves are expensive and of limited durability in test fluids. Therefore, we developed a cheap, fast, alternative method to mount valves obtained from the slaughterhouse in mock circuits.

Methods

Porcine aortic roots were obtained from the abattoir and used either in native condition or after fixation. Fixation was performed at a constant retrograde pressure to ensure closed valve position. Fixation time was 4 h in a 0.5%-glutaraldehyde phosphate buffer. The fixed valves were molded into a modular mock circulation connector using a fast curing silicone. Valve functionality was evaluated in a pulsatile setting (cardiac output = 4.7 l/min, heart rate = 80 beats/min) and compared before and after fixation. Leaflet motion was recorded with a high-speed camera and valve insufficiency was quantified by leakage flow under steady pressure application (80 mmHg).

Results

Under physiological conditions the aortic valves showed almost equal leaflet motion in native and fixed conditions. However, the leaflets of the native valves showed lower stiffness and more fluttering during systole than the fixed specimens. Under retrograde pressure, fresh and fixed valves showed small leakage flows of <30 ml/min.

Conclusions

The new mounting and fixation procedure is a fast method to fabricate low cost biologic valves for the use in mock circuits.
Nanoporous Activated Carbon Beads and Monolithic Columns as Effective Hemoadsorbents for Inflammatory Cytokines
Authors: Howell Carol A. , Sandeman Susan R. , Phillips Gary J. , Mikhalovsky Sergey V. , Tennison Stephen R. , Rawlinson Anthony P. , Kozynchenko Oleksandr P.
Published: August 2013

The aim of the present study was to develop and investigate nanoporous activated carbon materials for their ability to adsorb inflammatory cytokines directly from blood, for a range of therapeutic applications, including: systemic inflammatory response syndrome (SIRS) related to sepsis, cardio-pulmonary by-pass surgery, or ischemic reperfusion injury. Building on the previously established relationship between the porous structure of beaded polymer-derived activated carbon and its capacity to adsorb inflammatory molecules, we have developed and characterized monolithic porous carbon columns produced from the same polymer precursor matrix as carbon microbeads. The monolithic columns developed were assessed for their ability to adsorb inflammatory molecules from blood in a circulating system. Preliminary findings demonstrated good removal of the inflammatory cytokines IL-8 (100% removal), IL-6 (80% removal), and TNF (51% removal) from blood. The efficiency of cleansing is dependent on the size of the adsorbed molecule and the porous structure of the monolith, highlighting their potential for use as a hemoadsorption device.
The Impact of Inflammatory Factors Associated with Primary Arteriovenous Failure
Authors: Afsar Baris
Published: August 2013

Purpose

Very scarce data exist regarding the relationship between differential white blood cell (WBC) counts and primary arteriovenous fistula (AVF) failure. Thus, the current study aimed to investigate the specific relationship between primary AVF failure and differential WBC counts.

Methods

Sociodemographic, clinical, and laboratory parameters including automatically determined complete blood counts of the patients (from medical records and hospital charts) prior to AVF fistula surgery were recorded. Primary AVF failure was described as a complication of the AVF before the first successful cannulation for HD treatment.

Results

In total 94 patients (Male/Female: 49/45, Aged: 50.9 ∓ 15.0 years) were included. Ferritin, high sensitive C-reactive protein (hs-crp), total WBC count, neutrophil count, red cell distribution width (RDW) were higher in patients with primary AVF failure compared to patients without primary AVF failure. Logistic regression analysis showed that presence of diabetes (OR = 3.654, p = 0.035), RDW (OR = 0.449, p = 0.033) and ferritin (OR = 1.097, p = 0.021) were independently related with primary AVF failure.

Conclusions

Neither total WBC counts nor WBC subtypes were related with primary AVF failure. Higher RDW and ferritin levels had a prognostic value for development of primary AVF failure.
Using the Impella 5.0 with a Right Axillary Artery Approach as Bridge to Long-Term Mechanical Circulatory Assistance
Authors: Pozzi Matteo , Quessard Astrid , Nguyen Anthony , Mastroianni Ciro , Niculescu Michaela , Pavie Alain , Leprince Pascal
Published: August 2013

Purpose

Impella 5.0 is a short-term left ventricle assist device (LVAD), inserted retrograde into the left ventricle across the aortic valve through a surgical peripheral access. Impella has been utilized for various indications but in the setting of bridge-to-bridge application there are limited reports.

Methods

We performed a retrospective observational analysis of Impella utilization at our institution as bridge to long-term LVADs. The primary end-point was survival during Impella support.

Results

Between December 2010 and February 2012, we implanted 20 Impella in patients with cardiogenic shock and, among these, 5 were implanted as bridge to long-term LVADs. In this latter group, mean age at the time of implantation was 44 ∓ 15.6 (range 27-68) years and there was a prevalence of males (80%). Etiology of cardiogenic shock was: decompensated anthracycline-induced cardiomyopathy (n = 1), myocardial infarction (n = 4). There was no major bleeding requiring surgical revision or infectious complications at the right axillary access. One patient required Impella replacement due to a pump stop. After a mean period of 14.2 ∓ 9.0 (range 6-27) days of Impella support, patients were switched to a long-term LVAD (Jarvik 2000, n = 2; HeartMate II, n = 3). One patient died 70 days after implantation of the long-term LVAD due to multi-organ failure, while the remaining patients are still alive after a mean period of follow-up of 108.6 ∓ 66.2 (range 19-191) days.

Conclusions

Our experience shows that an Impella 5.0 implanted through the right axillary artery approach is a valid option as bridge to long-term LVADs.
Trends in Therapeutic Plasma Exchange: A Single-Center Evaluation
Authors: Vellinga Sanne , Verpooten Gert A. , van Doorn Karin Janssen
Published: August 2013

Purpose

The quality of evidence supporting the use of therapeutic plasma exchange (TPE) in the treatment of individual diseases and disorders is often limited. Since we have experienced a growing variety of indications in our center we decided to make an inventory of our TPE population.

Methods

Single-center retrospective inventory of adult TPE-patients during a 7-year period to determine the evolution of indications for TPE, the response to treatment, and the existing evidence supporting TPE in specified settings.

Results

During a period of 84 months, 72 patients underwent 638 sessions of TPE in 91 episodes. There was no shift in frequency of TPE or level of indication. Our population consisted of 69 patients. A level I indication was seen in 41 patients (59.4%), while 14 (20.3%) had a level II indication, 8 (11.6%) had a level III indication, one had a level IV indication (1.4%) and 5 patients suffered from a condition not mentioned in the guidelines (7.2%). The response rate was inversely correlated with the level of evidence after exclusion of these 5 patients (category I 97.6%, category II 71.4%, category III 50%, category IV 0% response, p<0.01).

Conclusions

There was no shift in frequency of TPE or level of indication in our center. Controversial indications should be carefully evaluated on an individual basis and a trial of TPE cannot be solely ruled out because of lack of evidence.
A Framework and Models for Evaluating the Multifare Dynamic Pricing Mechanism of Low-cost Carriers
Authors: Huang Kuancheng , Peng Yi-Ya , Wu I-Wen
Published: August 2013

In general, traditional airlines (legacy airlines or full-service airlines) develop multifare mechanisms and rely on seat inventory control to make quantity-based decisions. On the other hand, low-cost carriers (LCCs) tend to adopt the single-fare system and dynamically adjust the price. Nonetheless, more and more LCCs have begun to offer multiple-fare classes so as to take advantage of market segmentation and price discrimination. In order to evaluate the effectiveness of various revenue management (RM) mechanisms, the concept of willingness-to-pay is applied to model the customer choice with respect to RM control decisions. Dynamic programming–based models are then developed to provide a unified framework to evaluate the dynamic pricing mechanism of LCCs against the traditional seat inventory control policy that makes the open/close decisions of the fare classes with predetermined prices. Based on the numerical experiment, it is found that the former results in significantly higher revenue than the latter.
Frequent-Flier Programs as a Determinant in the Selection of Preferred Airlines by Corporations
Authors: Lubbe Berendien , Douglas Anneli , Wieme Lesley , Fabris-Rotelli Inger
Published: August 2013

Frequent-flier programs (FFPs) are used by airlines to generate loyalty and attract new customers. Research has shown that these programs significantly affect travelers' choice of airlines. In the managed travel environment where corporations select preferred airlines based on various determinants, it remains unclear whether these programs play a role in the selection process. A conceptual model of factors influencing corporate airline selection was formulated, positioning FFPs as one of the variables that may play a role. Exploratory factor analysis was done to test the conceptual model with the results showing that FFPs form part of business travelers' needs. Based on the results the conceptual model could be adjusted to provide the main factors and their related variables that influence corporate travel managers in selecting preferred airlines. It became evident that, within the boundaries of the study, frequent-flier programs were, in relation to other variables, generally not considered as important in the selection of a preferred airline by corporations.
The Importance of Completeness and Clarity in Air Transport Contracts in Remote Regions in Europe and Australia
Authors: Merkert Rico , Hensher David A.
Published: August 2013

This article compares the current experience of public service obligations carriers in Europe and Australia ex ante with regard to contract clarity, and then ex post regarding the completeness of their transport contracts. Particularly in times of government austerity, clear contracts are of immense importance to transport authorities in order to achieve value for money when procuring air-transport services. Weak contracts can result in uncertainties, transaction costs, and poor performance of regional airlines. Our results show differences across carriers that go beyond differences associated with geographic region, and highlight the importance of trust and good relationships between transport authorities and operators.
La Cultura de Paz en Nicaragua
Authors: Torres Denis
Published: August 2013

A partir de elementos tales como: el desarrollo de una mentalidad democrática en la clase política, el desarrollo institucional y constitucional, diversas expresiones organizativas de la sociedad civil, se muestra un incipiente pero importante cambio cultural en Nicaragua, favorable al desarrollo de una cultura de paz. DOI: http://dx.doi.org/10.5377/cultura.v19i60.1170 Cultura de Paz • Año XIX • N° 60 • Mayo - Agosto 2013 P / 2-4
La Visión del Informe Sandford en apoyo a Esquipulas II para fundamentar la cultura de paz en Centroamérica
Authors: Arríen Juan B
Published: August 2013

Juan Bautista Arríen, filósofo y educador, rescata, actualiza y destaca en su valor histórico el Informe Sandford para Centroamérica de 1989, el cual ubica a la pobreza como la raíz profunda de los conflictos violentos que agotaron la región en la década de los 80. El Informe Sandford identifica la paz, la democracia y desarrollo como el fundamento para una paz duradera y sostenible, coincidiendo con la UNESCO que ve en este triángulo interactivo la base de la cultura de paz DOI: http://dx.doi.org/10.5377/cultura.v19i60.1172 Cultura de Paz • Año XIX • N° 60 • Mayo - Agosto 2013 P / 10-16
Conflict management styles in academic and hospital pharmacy practice areas in affiliated tertiary institutions in Lagos, Nigeria
Authors: Emmanuel Anyika
Published: August 2013

Background/Objective: Types of conflicts in pharmacy organizations were discussed and conflict management styles by pharmacists in academia and hospital pharmacists in two affiliate tertiary institutions in Lagos, Nigeria were assessed. Methods: An adapted questionnaire of 20-item inventory for conflict management scale (CMS) for pharmacy was used to obtain responses from hospital pharmacists and pharmacists in academia in the practice areas. The multistage inventory item comprising questions that used four graded scales and appropriate alphabets A to D against each column was used in line with the described explanatory model. Scales of A, B, C, and D represent: imposing, settling, avoiding and thwarting respectively. Some items were rephrased and content-validated for clarity to respondents, while the last item (number 20) was introduced to reflect a pertinent issue in conflict management. The instrument was administered in voluntary situation over a period of two weeks; the results were collated and analyzed. Results: Thirty-one full-time pharmacist lecturers (14 males, 17 females) and 29 registered hospital pharmacists (6 males, 23 females) in the respective institutions completed the questionnaires. The summed scores of dominant and secondary conflict management styles for the two respective groups show that pharmacists in the two practice areas have different approaches to conflict management in workplace. A substantial number of respondents in both settings are either dominantly settling or avoiding in their style. Conclusion: Training in conflict management and reflective practice is highly recommended for pharmacists, to attain the skills that enhance their interpersonal environment, aimed at making pharmacy practice a very fulfilling and rewarding profession.
Bevacizumab Plus Chemotherapy as First-Line Treatment for Patients with Metastatic Colorectal Cancer: Results from a Spanish Observational Study
Authors: Pedro Salinas Hernández  , Rafael Trujillo Vilchez  , Antonio Arriví García-Ramos  , Rosana Grande Ladron de Guevara  , Angeles Rodríguez Jaraiz  , Pedro Gallurt Moreira  , Jose Maria Vieitez de Prado  , Miguel Ruiz López de Tejada  , Antonio Irigoyen Medina  , Juan Manuel Campos Cervera  , Juan Carlos Cámara Vicario  , Uriel Bohn Sarmiento  , Pedro López Tendero  , Juan Domingo Alonso Lajara  , Ana León Carbonero  , Marisa García de Paredes  , Juan de Alvaro Liaño  , Asunción Juarez Marroquí  , Luis López Gómez  , Diego Soto de Prado Otero
Published: August 2013

Background: This observational study evaluated the efficacy and safety of treatment with bevacizumab plus chemotherapy until disease progression (PD) in Spanish patients with metastatic colorectal cancer (mCRC). Methods: This multicentre, retrospective, observational analysis included patients receiving bevacizumab plus fluoropyrimidine-based chemotherapy as first-line treatment for mCRC who then developed PD. All patients received treatment in hospital oncology departments and none received bevacizumab as part of a clinical trial. Patients discontinuing treatment with bevacizumab for reasons other than PD were excluded. The primary endpoint was PFS; secondary endpoints were overall response rate (ORR) and safety. Results: Overall, 165 patients were evaluable for analysis: median age 63.0 years; male/female 62%/38%; ECOG performance status 0/1/2 55%/43%/2%. Median duration of bevacizumab treatment was 8.7 months. ORR was 48.5% (6 complete and 74 partial responses) and disease control rate was 74%. Median progression-free survival (PFS) was 8.4 months (95% CI 7.2-9.6). Patients receiving oxaliplatin- or irinotecan-based regimens had median PFS of 9.2 and 7.7 months, respectively; those receiving treatment not containing either oxaliplatin or irinotecan had a median PFS of 6.1 months. KRAS status did not have a statistically significant effect on PFS (9.5 vs. 7.8 months for KRAS wild-type vs. mutant tumours, respectively; p=0.647) or ORR (44.8% vs. 52.6%, respectively; p=0.391). The most common grade 3/4 adverse events were: diarrhoea (7%), paraesthesia (7%), neutropenia (3%), cutaneous toxicity (2%), and thrombocytopenia (2%). Conclusions: Treatment with bevacizumab plus standard chemotherapy is an effective and well-tolerated option for patients with mCRC who continue treatment until PD.
Hepatocellular Carcinoma Microvessel Density Quantitation with Image Analysis: Correlation with Prognosis
Authors: Amr Mohamed  , Shelley A. Caltharp  , Jason Wang  , Cynthia Cohen  , Alton B. Farris
Published: August 2013

Hepatocellular carcinoma (HCC) has a progression considered to be dependent on angiogenesis. Intratumoral microvessel density (MVD) has been associated with metastasis and recurrence risk; however, selection bias, counting errors, and lack of standardized assessment criteria have limited the clinical utility of angiogenesis quantitation. Therefore, we analyzed HCC angiogenesis with image cytometry using different methods and determined the correlation to prognosis. Tissue microarrays with 135 HCCs were CD31 and CD34 immunostained and quantitated with the Dako ACIS III Image Cytometer labeling index (LI) and Aperio Scanscope XT and MVD algorithm. LI and MVD were compared to each other and to pathologic features and prognosis (recurrence free survival). Using median cutoffs of microvesselquantitation, survival curve analysis showed a statistically significant difference between CD31 MVD algorithm measurement and prognosis (low MVD mean survival = 56.6 months and high MVD mean = 26.5 months; Log-Rank P = 0.0076). Survival was not significantly related to CD31 LI, CD34 LI or CD34 MVD. By linear regression, a direct correlation was observed between CD31 and CD34 using MVD (r = 0.45, P <0.0001), between CD31 MVD and CD31 LI (r = 0.55, P < 0.0001), and between CD31 LI and CD34 LI (r = 0.51, P < 0.0001). In addition, there was a weak but statistically significant relationship between CD31 MVD and CD34 LI (r = 0.25, P = 0.0050). Together, this data confirms previous studies linking angiogenesis to disease prognosis and suggests the utility of MVD image analysis algorithms.
A Review of the Expression of Genes Involved in Sex Steroid Hormone Metabolism in Prostate Tissue: A Need for Epigenetic Information
Authors: Jamie Ritchey  , Wilfried Karmaus  , Tara Sabo-Attwood  , Susan E. Steck  , Hongmei Zhang
Published: August 2013

There is strong clinical and laboratory evidence indicating that sex steroid hormones are important to the development and progression of prostate cancer, yet results from epidemiologic research conflicts. Examining gene expression in the sex steroid hormone pathway may uncover differences between cancerous and non-cancerous prostate tissues, yet our review using a pathway-oriented approach indicates that there is limited consistency across results, with the exception of GSTP1 found in the estrogen pathway, which was under-expressed in cancerous prostate tissue. This agrees with past studies that reported GSTP1 is methylated in prostate cancer. With new cost-effective technology, we can screen for epigenetic markers, like methylation, which can be applied in epidemiological studies. A clearer understanding of gene expression and epigenetic mechanisms in prostate cancer may contribute to improving prevention, diagnosis, and treatment.
Salivary Diagnosis: Detection of Several Intracellular Enzymes in Patients with Oral Lichen Planus
Authors: Miricescu Daniela  , Totan Alexandra  , Calenic Bogdan  , Parlatescu Ioanina  , Mohora Maria  , Greabu Maria
Published: August 2013

Introduction: Oral lichen planus is a chronic inflammatory disease, presenting malignant potential. An association between chronic inflammation and initiation and progression of cancer has long been established. Aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase and gammaglutamil transferase are intracellular enzymes associated with cell injury and cell death. The main aim of the present study is to evaluate changes of enzymatic activity of mentioned enzymes in saliva and serum of patients with oral lichen planus.
Materials and Methods: 20 patients with oral lichen planus and 20 healthy controls were included in the present study. Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and gammaglutamil transferase (GGT) were detected in both serum and saliva.
Results and Discussions: Salivary levels of ALP were decreased while LDH levels were increased in patients with oral lichen planus vs controls (p<0.05). At the same time GGT and AST levels were decreased (not significantly significant) in oral lichen planus patients and control groups. Serum levels of ALP were markedly increased while GGT was found decreased in patients vs. controls (p<0.05). AST and LDH were decreased but not significantly in oral lichen planus patients as compared to controls.
Conclusions: Our results reflect increased levels for salivary LDH and serum ALP in patients with oral lichen panus. Saliva can be used as a new diagnostic fluid to detect certain biomarkers such as enzymes in patients with oral lichen planus.
Efficacy of Chemiluminescence (ViziLite™) as a Screening Method in the Detection of Clinically Suspicious Oral Cancerous and Precancerous Lesions
Authors: Antonio Carrera Torres  , Ángel Martínez-Sahuquillo Márquez  , Javier Fernández Farhall  , María José Cobos Fuentes  , Isabel Gallardo Castillo
Published: August 2013

Several screening techniques based on light interaction with tissue have been described to aid clinicians in the detection of early oral cancerous lesions. One of the most studied techniques is chemiluminescence. This method has been used in different studies but always by Oral Medicine specialists.
Objective: To evaluate the chemiluminescence system as a screening method in the detection of clinically suspicious cancerous and precancerous oral lesions when used by clinicians without an Oral Medicine Speciality.
Study Design: A total of 100 patients attending the Oral Medicine Unit at the Dental School of the University of Seville were enrolled. All patients were current smokers and were above the age of 40. The clinical examination was performed by dental students who were instructed in the location and recognition of potentially malignant oral disorders, using visual examination and the chemiluminescence test ViziLite Plus  (Zila Pharmaceuticals, Phoenix, AZ, USA). To assess the validity of the chemiluminescence test as a screening method, a visual exam was performed by a specialist in Oral Medicine which was used as a gold-standard.
Results: Conventional oral visual examination by the Oral Medicine Specialist found 13 lesions suspicious for malignancy, out of which 7 were also detected using the chemiluminescence test. Furthermore, 87 patients were diagnosed as lesion-free, of which 49 obtained negative results during the chemiluminescence test and 38 patients had some sort of lesion. With these results, the test yielded a sensitivity of 0.56 and a specificity of 0.56. These results indicate values similar to other studies, in fact lower sensitivity values, possibly due to the lack of experience of the clinician.
Conclusions: The chemiluminescence test (ViziLite Plus) did not present any advantages in terms of cost-benefit compared to conventional examination as a screening method for cancerous and precancerous oral lesions.
A Comparative Economic Analysis of Immunization Programs for Pertussis and Measles: The Use of ARIMA Model to Study the Epidemiological Situation in England and Wales
Authors: Girard Dorota Zdanowska
Published: August 2013

Objective: We evaluate pertussis and measles immunization strategies and compare the consequences in terms of health effects and economic costs.
Methods: Based on epidemiological data for pertussis and measles in England and Wales from 1970 to 2012, we use ARIMA approach to model the relation between notification cases and vaccination coverage for each disease. We then perform an economic evaluation of vaccination programs at 95% and discuss the benefits for the society to achieve this level when compared with lower vaccination rates currently observed. The advantages for the society of increasing vaccination coverage up to 98% are considered respectively for pertussis and measles.
Results: The programs at a 95% vaccination rate, which is able to significantly reduce the mortality and the morbidity due to pertussis and measles, are confirmed to be the best cost saving immunization strategy. The total social net benefits are systematically maximized when the programs are compared to strategies with lower vaccination coverage. The decision to exceed the herd immunity level and reach the rate at 98% is economically justified for measles, while for pertussis the programs at 98% are less cost effective than the programs at 95%.
Conclusion: Additional efforts must be carried out to promote measles vaccination since immunization strategies at 95% and at higher rates are recommended on epidemiological and economic grounds.
Prediction of Childhood Asthma Using Conditional Probability and Discrete Event Simulation
Authors: Monleón-Getino T. , Puig C. , Vall O. , Ríos M. , Chiandetti A. , Garcia-Algar O.
Published: August 2013

Asthma prevalence in children and adolescents in Spain is 10-17%. It is the most common chronic illness during childhood. Prevalence has been increasing over the last 40 years and there is considerable evidence that, among other factors, continued exposure to cigarette smoke results in asthma in children. No statistical or simulation model exist to forecast the evolution of childhood asthma in Europe. Such a model needs to incorporate the main risk factors that can be managed by medical authorities, such as tobacco (OR = 1.44), to establish how they affect the present generation of children. A simulation model using conditional probability and discrete event simulation for childhood asthma was developed and validated by simulating realistic scenario. The parameters used for the model (input data) were those found in the bibliography, especially those related to the incidence of smoking in Spain. We also used data from a panel of experts from the Hospital del Mar (Barcelona) related to actual evolution and asthma phenotypes. The results obtained from the simulation established a threshold of a 15-20% smoking population for a reduction in the prevalence of asthma. This is still far from the current level in Spain, where 24% of people smoke. We conclude that more effort must be made to combat smoking and other childhood asthma risk factors, in order to significantly reduce the number of cases. Once completed, this simulation methodology can realistically be used to forecast the evolution of childhood asthma as a function of variation in different risk factors.
Analysis of Risk and Protective Factors for Arthritis Status and Severity Using Survey Data
Authors: Teramoto Masaru , Moonie Sheniz
Published: August 2013

This study looked at how cigarette smoking, alcohol consumption, obesity, and physical activity are associated with the prevalence and severity of arthritis among adults living in Delaware, U.S. through the analysis of survey data. We examined data from the 2009 Delaware Behavioral Risk Factor Surveillance System (BRFSS). Weighted percentages were calculated for the arthritis-related factors above by arthritis status and activity limitation due to arthritis/joint symptoms, and were analyzed using the Rao-Scott χ2 test. A multiple logistic regression analysis was performed to determine an odds ratio (OR) while adjusting for gender, age, race/ethnicity, and education. Adult Delawareans self-reporting arthritis were more likely to be former and current smokers than those without self-reported arthritis (p < 0.001; OR = 1.58 for former smokers vs. non-smokers; OR = 1.52 for current smokers vs. non-smokers). Moderate and heavy alcohol consumption was associated with lower severity of arthritis (p < 0.001; OR = 0.66 for moderate drinking vs. no drinking; OR = 0.50 for heavy drinking vs. no drinking). There was a significant relationship of obesity to both arthritis status (p < 0.001; OR = 2.13 for obesity vs. not overweight/obesity) and severity (p < 0.008; OR = 1.67 for obesity vs. not overweight/obesity). Furthermore, people having arthritis-related activity limitation were more likely to not meet the current physical activity recommendations (p = 0.013; OR = 1.46). It appears that smoking and obesity have a negative impact on the risk and severity of arthritis, whereas alcohol consumption and physical activity may be protective against arthritis. A proper analysis of survey data is essential to truly understand how human behavior impacts people’s health.
Analysis of Genetic Relationship Among 11 Iranian Ethnic Groups with Bayesian Multidimensional Scaling Using HLA Class II Data
Authors: Zare Najaf , Farjadian Shirin , Maleknia Samaneh
Published: August 2013

Background: The key feature of Bayesian methods is their lack of dependence on defaults necessary for classical statistics. Because of the high volume of simulation, Bayesian methods have a high degree of accuracy. They are efficient in data mining and analyzing large volumes of data, and can be upgraded by entering new data.
Objective: We used Bayesian multidimensional scaling (MDS) to analyze the genetic relationships among 11 Iranian ethnic groups based on HLA class II data.
Method: Allele frequencies of three HLA loci from 816 unrelated individuals belonging to 11 Iranian ethnic groups were analyzed by Bayesian MDS using R and WinBUGS software.
Results: like the results of correspondence analysis as a prototype of classical MDS analysis, the results of Bayesian MDS also showed Arabs from Famur, Balochis, Zoroastrians and Jews to be separate from other Iranian ethnic groups. Decreases stress in Bayesian MDS method compared to classical method revealed the accuracy of Bayesian MDS for HLA data analyses.
Conclusion: This study reports the first application of Bayesian multidimensional scaling to HLA data analysis with Nei’s DA genetic distances. Stress reduction in Bayesian MDS compared to classical MDS showed that the Bayesian approach can improve the accuracy of genetic data analysis.
An Application of Gamma Generalized Linear Model for Estimation of Survival Function of Diabetic Nephropathy Patients
Authors: Grover Gurprit , Alka Sabharwal Alka Sabharwal , Mittal Juhi
Published: August 2013

Diabetic nephropathy (DN) is a generic term referring to deleterious effect on renal structure and/or function caused by diabetes mellitus. World Health Organization estimates that diabetes affects more than 170 million people worldwide and this number may rise to 370 million by 2030. The rate of rise in Serum Creatinine (SrCr) is a well-accepted marker for the progression of Diabetic Nephropathy (DN). In this paper, survival functions of type 2 diabetic patients with renal complication are estimated. Firstly, most appropriate distribution for duration of diabetes is selected through minimum Akaike Information Criterion value, Gamma distribution is found to be an appropriate model. Secondly, the parameters estimates of the selected distribution are obtained by fitting a Generalized Linear Model (GLM), with duration of diabetes as the response variable and predictors as SrCr and number of successes (number of times SrCr values exceed its normal range (1.4 mg/dl)). These covariates are linked with the response variable using two different link functions namely log and reciprocal links. Using the estimates of parameters obtained from generalized linear regression analysis, survival functions for different durations under both the links are estimated. Further we compared the estimated survival functions under both the links with Kaplan Meier (KM) estimates graphically. Findings suggested that the Kaplan Meier estimate and Gamma distribution under both links provided a close estimate of survival functions. Median survival time is 16.3 years and 16.8 years obtained from KM method and Gamma GLM respectively.
Observation-Driven Model for Zero-Inflated Daily Counts of Emergency Room Visit Data
Authors: Sneddon Gary , Bari Wasimul , Hasan M. Tariqul
Published: August 2013

Time series data with excessive zeros frequently occur in medical and health studies. To analyze time series count data without excessive zeros, observation-driven Poisson regression models are commonly used in the literature. As handling excessive zeros in count data is not straightforward, observation-driven models are rarely used to analyze time series count data with excessive zeros. In this paper an observation-driven zero-inflated Poisson (ZIP) model for time series count data is proposed. This approach can accommodate an autoregressive serial dependence structure which commonly appears in time series. The estimation of the model parameters by using the quasi-likelihood estimating equation approach is discussed. To estimate the correlation parameters of the dependence structure, a moment approach is used. The proposed methodology is illustrated by applying it to a data set of daily emergency room visits due to bronchitis.
The Methodology of Human Diseases Risk Prediction Tools
Authors: Mannan H. , Ahmed R. , Sanagou M. , Ivory S. , Wolfe R.
Published: August 2013

Disease risk prediction tools are used for population screening and to guide clinical care. They identify which individuals have particularly elevated risk of disease. The development of a new risk prediction tool involves several methodological components including: selection of a general modelling framework and specific functional form for the new tool, making decisions about the inclusion of risk factors, dealing with missing data in those risk factors, and performing validation checks of a new tool’s performance. There have been many methodological developments of relevance to these issues in recent years. Developments of importance for disease detection in humans were reviewed and their uptake in risk prediction tool development illustrated. This review leads to guidance on appropriate methodology for future risk prediction development activities.
De la Guerra de los Treinta Años a la yihad en el siglo XXI: el conflicto religioso, ¿preludio de la secularización?
Authors: DerGhougassian Khatchik
Published: August 2013

The “return of religion” in international politics is an observable phenomenon since the 1980s. From the perspective of IR Theory, positivist schools do not consider the religious factor an independent variable explaining the current global conflict; whereas post-positivists have gone as far as to advocate for a proper field of study. Is the “return of the religion” conceptually announcing the end of the secular era and all the Modern rationale for the study of the political dynamics? This study departs from this question to focus on the lines of fracture within the Islam to argue that in fact Jihad in the 21st century might well be the very sign of the last war of secularization.
Detection of Influenza Virus with Specific Subtype by Using Localized Surface Plasmons Excited on a Flat Metal Surface
Authors: Ning Jun , Nagata Kotaro , Ainai Akira , Hasegawa Hideki , Kano Hiroshi
Published: August 2013

We report on a method to determine subtype of influenza viruses by using surface plasmons localized in microscopic region on a flat metal surface. In this method, refractive index variation arisen from interactions between viruses and their monoclonal antibodies is measured. The developed sensor shows stability of refractive index in the order of 10-4 against sample exchange. In our experiment, A/H1N1 viruses are distinguished from A/H3N2 viruses by using monoclonal antibodies immobilized on the metal surface. Since the measurement probe has the volume of ∼6 al, the method has potential to handle multiple subtypes in the measurement of a sample with ultra small volume.
Biopolymer Templated Glass with a Twist: Controlling the Chirality, Porosity, and Photonic Properties of Silica with Cellulose Nanocrystals
Authors: Shopsowitz Kevin E. , Kelly Joel A. , Hamad Wadood Y. , MacLachlan Mark J.
Published: August 2013

A detailed investigation of the formation and properties of mesoporous silica templated by the chiral nematic liquid crystal phase of cellulose nanocrystals (CNCs) is presented. Under appropriate conditions, CNCs co‐assemble with silica up to loadings of ≈60 wt% to give composite films with periodic chiral nanostructures. The periodicity of these films can be readily controlled to obtain materials that selectively reflect light with wavelengths ranging from ≈400–1400 nm. The co‐assembly of CNCs and silica into ordered chiral nematic structures is demonstrated to occur within a narrow window of pH and is affected by aging: a slow rate of silica condensation appears to be vital for the formation of well‐ordered materials. CNCs can be removed from the composite films by calcination or acid hydrolysis to give high surface area chiral nematic mesoporous silica (CNMS) with tunable pore diameters. The combination of mesoporosity and chiral nematic ordering in CNMS enables it to be used in a unique way for refractometric sensing applications. It is shown that, when using circular dichroism (CD) signals to monitor the chiral photonic properties of CNMS, variations in refractive index can be detected based on changes of both CD signal intensity and peak position with good sensitivity.
Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors
Authors: Falchi Lorenzo , Kantarjian Hagop M. , Wang Xuemei , Verma Dushyant , Quintás‐Cardama Alfonso , O'Brien Susan , Jabbour Elias J. , Ravandi‐Kashani Farhad , Borthakur Gautam , Garcia‐Manero Guillermo , Verstovsek Srdan , Burger Jan A. , Luthra Raja , Cortes Jorge E.
Published: August 2013

Most patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKI) achieve complete cytogenetic response (CCyR). An increasing number of patients also achieve deep molecular responses (MR). We determined the frequency and significance of deep MR after TKI therapy for CML in CP. MR included: major molecular response (MMR), MR4, MR4.5, and undetectable transcripts (UND), i.e., BCR‐ABL/ABL of ≤0.1, ≤0.01, ≤0.0032%, and undetectable transcripts, respectively. Four hundred eighty‐three patients received imatinib 400 mg/day (IM400, 71, July 2000 to April 2001), imatinib 800 mg/day (IM800, 204, June 2001 to July 2005), nilotinib (106, July 2005 to date), or dasatinib (102, November 2005 to date). UND rates at 36 months were 18.1, 30.6, 29.2, and 28.6%, respectively. Patients achieving UND have superior transformation‐free survival (TFS) and overall survival (OS) versus those obtaining ≤MMR, but not other MR levels. At the 18‐ and 24‐month landmark analysis, patients achieving UND have no advantage in TFS and OS compared to those achieving a lesser degree of MR. Among patients achieving MR4.5, those who maintain it for ≥2 years (susMR4·5) have no additional benefit in TFS or OS. Most patients with early CP CML receiving TKI achieve MMR. BCR‐ABL transcripts become undetectable in a significant fraction of them. Deeper MR at 18 or 24 months are not associated with a benefit in TFS or OS. Furthermore, achieving susMR4·5 does not appear to further reduce the risk of transformation or death. Am. J. Hematol. 88:1024–1029, 2013. © 2013 Wiley Periodicals, Inc.
Associations between arterial oxygen saturation, body size and limb measurements among high‐altitude andean children
Authors: Pomeroy Emma , Stock Jay T. , Stanojevic Sanja , Miranda J. Jaime , Cole Tim J. , Wells Jonathan C.K.
Published: August 2013

Objectives

The relative influences of hypoxia and other environmental stressors on growth at altitude remain unclear. Previous work demonstrated an association between peripheral arterial oxygen saturation (SpO2) and anthropometry (especially tibia length) among Tibetan and Han children at altitude. We investigated whether similar associations exist among Andeans, and the patterning of associations between SpO2 and anthropometry.

Methods

Stature, head‐trunk height, total upper and lower limb lengths, zeugopod (ulna and tibia) and autopod (hand and foot) lengths were measured in Peruvian children (0.5–14 years) living at >3000 m altitude. SpO2 was measured by pulse oximetry. Anthropometry was converted to internal z scores. Correlation and multiple regression were used to examine associations between anthropometry z scores and SpO2, altitude, or SpO2 adjusted for altitude since altitude is a major determinant of variation in SpO2.

Results

SpO2 and altitude show weak, significant correlations with zeugopod length z scores and still weaker significant correlations with total upper and lower limb length z scores. Correlations with z scores for stature, head‐trunk height, or autopod lengths are not significant. Adjusted for altitude, there is no significant association between anthropometry and SpO2.

Conclusions

Associations between SpO2 or altitude and total limb and zeugopod length z scores exist among Andean children. However, the relationships are relatively weak, and while the relationship between anthropometry and altitude may be partly mediated by SpO2, other factors that covary with altitude (e.g., socioeconomic status, health) are likely to influence anthropometry. The results support suggestions that zeugopod lengths are particularly sensitive to environmental stressors. Am. J. Hum. Biol., 25:629–636, 2013. © 2014 The Authors. AMERICAN JOURNAL OF HUMAN BIOLOGY Published by Wiley Periodicals, Inc.
Gene x environment interactions impact endometrial function and the menstrual cycle: PROGINS, life history, anthropometry, and physical activity
Authors: Rowe Elizabeth J. , Eisenstein Toby K. , Meissler Joseph , Rockwell L. Christie
Published: August 2013

Objectives

We assessed the impact of a high frequency, functionally significant allelic variant of the progesterone receptor gene (PROGINS) on endometrial function and menstrual cycle characteristics. Further we asked whether PROGINS moderates the impact of life history characteristics, anthropometric measures, and physical activity on endometrial function.

Methods

Fifty‐two women were genotyped for the PROGINS variant, provided life history information, and had anthropometric measurements made. Women monitored their menstrual bleeding for three cycles, performed mid‐cycle urinary ovulation tests, and recorded physical activity. A subset of women provided daily saliva samples and had mid‐luteal endometrial thickness measurements taken during the third menstrual cycle. Salivary progesterone was assayed using ELISAs. The direct impact of PROGINS on endometrial and menstrual cycle characteristics was determined via independent t‐tests with Bonferroni correction. Interactions between PROGINS and covariates were assessed by moderated regression.

Results

PROGINS did not directly impact any indicator of endometrial function. However, PROGINS caused an increase in menstrual cycle length with increasing mid‐luteal progesterone levels; the opposite relationship was present in noncarriers (P < 0.05). Additionally, PROGINS interacted with four of six anthropometric measures (BMI, waist circumference, height, and waist‐hip ratio) to impact endometrial function, however, interactions between PROGINS and life history variables, or physical activity was limited.

Conclusions

The gene x environment interactions we report suggest that PROGINS alters endometrial sensitivity to maternal energetic condition. Thus, the possibility of genetically‐based variation in sensitivity to energetic stress should be considered in future adaptive models of women's reproduction. Am. J. Hum. Biol. 25:681–694, 2013. © 2013 Wiley Periodicals, Inc.
Angelman syndrome in Denmark. Birth incidence, genetic findings, and age at diagnosis
Authors: Mertz Line Granild Bie , Christensen Rikke , Vogel Ida , Hertz Jens Michael , Nielsen Karen Brøndum , Grønskov Karen , Østergaard John R.
Published: August 2013

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2–q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were to examine the birth incidence of AS in Denmark and to characterize the size of the 15q11.2–q13 deletions with 1,000K array CGH. In addition, we analyzed genotype differences in regard to age at diagnosis and investigated the occurrence of deletions/duplications outside the 15q11.2–q13 regions. We identified 51 patients with genetically verified AS, which corresponded to a birth incidence of 1:24,580 (95%CI: 1:23,727–1:25,433). Thirty‐six patients showed a deletion; 13 had a Class I deletion and 20 had a Class II deletion. There was bimodal distribution of the BP3 breakpoint. Three patients had larger and atypical deletions, with distal breakpoints telomeric to BP3. Five patients had paternal uniparental disomy (pUPD) of chromosome 15, and four had a verified UBE3A mutation. Additional deletions/duplications outside the 15q11.2–q13 areas were demonstrated in half the participants. Six harbored more than one CNV. Mean age at diagnosis was 21 months (95%CI: 17–23 months) for children with a deletion and 46 months (95%CI: 36–55 months) for children with pUPD or a UBE3A mutation (P < 0.01). The presence of a CNV outside 15q11.2–q13 did not have an impact on age at diagnosis. © 2013 Wiley Periodicals, Inc.