bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Interaction and DNA Cleavage Studies of a New Platinum(II) Complex Containing Aliphatic and Aromatic Dinitrogen Ligands
Authors: Shahabadi Nahid , Kashanian Soheila , Mahdavi Maryam , Sourinejad Noorkaram
Published: December 2011

A new Pt(II) complex, [Pt(DIP)(LL)](NO3)2(in which DIP is 4,7-diphenyl-1,10-phenanthroline and LL is the aliphatic dinitrogen ligand,N,N-dimethyl-trimethylenediamine), was synthesized and characterized using different physico-chemical methods. The interaction of this complex with calf thymus DNA (CT-DNA) was investigated by absorption, emission, circular dichroism (CD), and viscosity measurements. The complex binds to CT-DNA in an intercalative mode. The calculated binding constant,Kb, was  M−1. The enthalpy and entropy changes of the reaction between the complex and CT-DNA showed that the van der Waals interactions and hydrogen bonds are the main forces in the interaction with CT-DNA. In addition, CD study showed that phenanthroline ligand insert between the base pair stack of double helical structure of DNA. It is remarkable that this complex has the ability to cleave the supercoiled plasmid.
Secondary Bilateral Angle Closure Glaucoma due to Topiramate
Authors: Paciuc-Beja Miguel , Retchkiman-Bret Myriam , Velasco-Barona Cecilio Francisco , Galicia-Alfaro Victor Hugo
Published: December 2011

We examined a 39-year-old female with severe headache and blurred vision. She was on topiramate, 50 mg once a day for one week because of migraine. Periorbital edema, chemosis, myopia, high intraocular pressures, and shallow anterior chambers were present at the initial examination. Iridocorneal angles were closed, ultrasound showed choroidal effusions. We stopped topiramate and started antiglaucoma treatment. After one week the intraocular pressure was 10 mm Hg in both eyes without treatment. A new ultrasound showed no choroidal effusions. Topiramate has been associated with acute secondary angle closure glaucoma as an idiosyncratic reaction to the drug. Physicians prescribing topiramate need to alert patients of this potential sight-threatening idiosyncratic reaction.
Effect of Intravitreal Ranibizumab in the Treatment of Peripapillary Choroidal Neovascularisation
Authors: Hamoudi Hassan , Sørensen Torben Lykke
Published: December 2011

Intravitreal ranibizumab therapy is widely used in treatment of subfoveal choroidal neovascularisation (CNV) in age-related macular degeneration. We wanted to study the effect of intravitreal ranibizumab therapy in peripapillary CNV. A prospective recording of treatment outcomes in twelve eyes (12 patients) with peripapillary CNV with intravitreal injections of ranibizumab was performed. The patients received a series of 3 injections 4–6 weeks apart, and then a new ophthalmic examination was made including OCT and further therapy was given if the peripapillary CNV was still active. Nine patients had idiopathic peripapillary CNV, and in 3 patients it was associated to age-related macular degeneration. Followup had to be at least 6 months. The mean follow-up time was 15.9 (range 9–27) months and the mean number of injections 6.2 (3–10). In 10 patients treatment had resulted in an inactivation of the peripapillary CNV, but 3 of them had reactivation, while 2 patients had no inactivation. Currently, 5 patients are continuous to receive treatment. VA improved in 10 patients. Intravitreal ranibizumab therapy appears to be effective in patients with peripapillary CNV, but in some cases there is repeated reactivation or continuous activity of the peripapillary CNV.
Yaws in the Western Pacific Region: A Review of the Literature
Authors: Capuano Corinne , Ozaki Masayo
Published: December 2011

Until the middle of the 20th century, yaws was highly endemic and considered a serious public health problem in the Western Pacific Region (WPR), leading to intensive control efforts in the 1950s–1960s. Since then, little attention has been paid to its reemergence. Its current burden is unknown. This paper presents the results of an extensive literature review, focusing on yaws in the South Pacific. Available records suggest that the region remains largely free of yaws except for Papua New Guinea, Solomon Islands, and Vanuatu. Many clinical cases reported recently were described as “attenuated”; advanced stages are rare. A single intramuscular injection of benzathine penicillin is still effective in curing yaws. In the Pacific, yaws may be amenable to elimination if adequate resources are provided and political commitment revived. A mapping of yaws prevalence in PNG, Solomon, and Vanuatu is needed before comprehensive country-tailored strategies towards yaws elimination can be developed.
Some New Constructions of Authentication Codes with Arbitration and Multi‐Receiver from Singular Symplectic Geometry
Authors: Gao You , Yu Huafeng
Published: December 2011

A new construction of authentication codes with arbitration and multireceiver from singular symplectic geometry over finite fields is given. The parameters are computed. Assuming that the encoding rules are chosen according to a uniform probability distribution, the probabilities of success for different types of deception are also computed.
An Investigation on the Nonlinear Free Vibration Analysis of Beams with Simply Supported Boundary Conditions Using Four Engineering Theories
Authors: Jafari-Talookolaei R. A. , Kargarnovin M. H. , Ahmadian M. T. , Abedi M.
Published: December 2011

The objective of this study is to present a brief survey on the geometrically nonlinear free vibrations of
the Bernoulli‐Euler, the Rayleigh, shear, and the Timoshenko beams with simple end conditions using the Homotopy
Analysis Method (HAM). Expressions for the natural frequencies, the transverse deflection, postbuckling
load‐deflection relation to, and critical buckling load are presented. The results of nonlinear analysis are
validated with the published results, and excellent agreement is observed. The effects of some parameters,
such as slender ratio, the rotary inertia, and the shear deformation, are examined as other parameters are
fixed.
The Carnivore Connection Hypothesis: Revisited
Authors: Brand-Miller Jennie C. , Griffin Hayley J. , Colagiuri Stephen
Published: December 2011

The “Carnivore Connection” hypothesizes that, during human evolution, a scarcity of dietary carbohydrate in diets with low plant : animal subsistence ratios led to insulin resistance providing a survival and reproductive advantage with selection of genes for insulin resistance. The selection pressure was relaxed at the beginning of the Agricultural Revolution when large quantities of cereals first entered human diets. The “Carnivore Connection” explains the high prevalence of intrinsic insulin resistance and type 2 diabetes in populations that transition rapidly from traditional diets with a low-glycemic load, to high-carbohydrate, high-glycemic index diets that characterize modern diets. Selection pressure has been relaxed longest in European populations, explaining a lower prevalence of insulin resistance and type 2 diabetes, despite recent exposure to famine and food scarcity. Increasing obesity and habitual consumption of high-glycemic-load diets worsens insulin resistance and increases the risk of type 2 diabetes in all populations.
On Six Solutions for m‐Point Differential Equations System with Two Coupled Parallel Sub‐Super Solutions
Authors: Liu Jian , Su Hua , Wang Shuli
Published: December 2011

Under the assumption of two coupled parallel subsuper solutions, the existence of at least six solutions for a kind of second‐order m‐point differential equations system is obtained using the fixed point index theory. As an application, an example to demonstrate our result is given.
The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis
Authors: Antunes Ricardo F. , Kaski Juan Carlos , Dumitriu Ingrid E.
Published: December 2011

Atherosclerosis is a chronic inflammatory disease that is mediated by both the innate and adaptive immune responses. T lymphocytes, that together with B cells are the cellular effectors of the adaptive immune system, are currently endowed with crucial roles in the development and progression of atherosclerosis. Costimulatory receptors are a class of molecules expressed by T lymphocytes that regulate the activation of T cells and the generation of effector T-cell responses. In this review we present the roles of costimulatory receptors of the tumour necrosis factor receptor (TNFR) superfamily in atherosclerosis and discuss the implications for future therapies that could be used to specifically modulate the immune response of pathogenic T cells in this disease.
Androgens and Adipose Tissue in Males: A Complex and Reciprocal Interplay
Authors: Mammi Caterina , Calanchini Matilde , Antelmi Antonella , Cinti Francesca , Rosano Giuseppe M. C. , Lenzi Andrea , Caprio Massimiliano , Fabbri Andrea
Published: December 2011

Clinical evidence shows that in males obesity is frequently associated with hypogonadism and vice versa; also, low testosterone levels have been considered a “hallmark” of metabolic syndrome in men. These observations indicate that there is a strict connection between anatomically and functionally distinct cell types such as white adipocytes and Leydig cells, that synthesize testosterone. Adipose tissue is able to control several functions of the testis through its products secreted in the bloodstream. On the other hand, circulating levels of testosterone and estradiol deeply affect adipocyte proliferation, differentiation, and fat mass distribution, hereby controlling critical metabolic functions, such as food intake, insulin sensitivity, vascular reactivity, and immunity. This paper highlights the existing clinical and experimental evidence linking androgens and adipose tissue and illustrates the consequences occurring when the balance between fat mass distribution and eugonadism is lost.
Suspended Decoupler: A New Design of Hydraulic Engine Mount
Authors: Christopherson J. , Mahinfalah M. , Jazar Reza N.
Published: December 2011

Because of the density mismatch between the decoupler and surrounding fluid, the decoupler of all hydraulic engine mounts (HEM) might float, sink, or stick to the cage bounds, assuming static conditions. The problem appears in the transient response of a bottomed-up floating decoupler hydraulic engine mount. To overcome the bottomed-up problem, a suspended decoupler design for improved decoupler control is introduced. The new design does not noticeably affect the mechanism's steady-state behavior, but improves start-up and transient response. Additionally, the decoupler mechanism is incorporated into a smaller, lighter, yet more tunable and hence more effective hydraulic mount design. The steady-state response of a dimensionless model of the mount is examined utilizing the averaging perturbation method applied to a set of second-order nonlinear ordinary differential equations. It is shown that the frequency responses of the floating and suspended decoupled designs are similar and functional. To have a more realistic modeling, utilizing nonlinear finite elements in conjunction with a lumped parameter modeling approach, we evaluate the nonlinear resorting characteristics of the components and implement them in the equations of motion.
Cooperation between c-Met and Focal Adhesion Kinase Family Members in Medulloblastoma and Implications for Therapy
Authors: Guessous Fadila , Yang Yanzhi , Johnson Elizabeth , Marcinkiewicz Lukasz , Smith Matthew , Zhang Ying , Kofman Alexander , Schiff David , Christensen James , Abounader Roger
Published: December 2011

We previously showed the involvement of the tyrosine kinase receptor c-Met in medulloblastoma malignancy. The nonreceptor tyrosine kinases focal adhesion kinase (FAK) and Pyk2 are key players in the progression of different cancers. However, their role in medulloblastoma malignancy is not well understood. In this study, using a protein array approach, we found that c-Met induces FAK and Pyk2 phosphorylation in medulloblastoma cells. We therefore studied the interactions between c-Met and FAK/Pyk2 and their implications for medulloblastoma therapy. We found that c-Met activates FAK and Pyk2 in several medulloblastoma cell lines. We also found that FAK and Pyk2 mediate the malignant effects of c-Met on medulloblastoma cell proliferation, migration, and invasion. On the basis of these findings, we hypothesized that combined c-Met and FAK inhibitions would have additive effects on the inhibition of medulloblastoma malignancy. To test this hypothesis, we assessed the effects on medulloblastoma malignancy parameters of single or combined treatments of medulloblastoma cells with c-Met and FAK small-molecule kinase inhibitors. We found a significant increase in the inhibitory effect of both inhibitors on medulloblastoma cell migration and cell invasion as compared with single inhibitions (P < 0.05). In addition, oral gavage treatment with c-Met inhibitor of mice bearing medulloblastoma xenografts significantly reduced in vivo tumor growth. Therefore, combining c-Met inhibitors with FAK inhibitors constitutes a new potential strategy for medulloblastoma therapy. Altogether, our study describes a role for FAK and Pyk2 in medulloblastoma malignancy, uncovers new interactions between c-Met and FAK/Pyk2, and proposes for the first time combining anti-c-Met and anti-FAK inhibitors as a new strategy for medulloblastoma therapy. Mol Cancer Ther; 11(2); 288–97. ©2011 AACR.
Low-Dose Metronomic Oral Dosing of a Prodrug of Gemcitabine (LY2334737) Causes Antitumor Effects in the Absence of Inhibition of Systemic Vasculogenesis
Authors: Francia Giulio , Shaked Yuval , Hashimoto Kae , Sun John , Yin Melissa , Cesta Carolyn , Xu Ping , Man Shan , Hackl Christina , Stewart Julie , Uhlik Mark , Dantzig Anne H. , Foster F. Stuart , Kerbel Robert S.
Published: December 2011

Metronomic chemotherapy refers to the close, regular administration of conventional chemotherapy drugs at relatively low, minimally toxic doses, with no prolonged break periods; it is now showing encouraging results in various phase II clinical trials and is currently undergoing phase III trial evaluation. It is thought to cause antitumor effects primarily by antiangiogenic mechanisms, both locally by targeting endothelial cells of the tumor neovasculature and systemically by effects on bone marrow–derived cells, including circulating endothelial progenitor cells (CEP). Previous studies have shown reduction of CEPs by metronomic administration of a number of different chemotherapeutic drugs, including vinblastine, cyclophosphamide, paclitaxel, topotecan, and tegafur plus uracil (UFT). However in addition to, or even instead of, antiangiogenic effects, metronomic chemotherapy may cause suppression of tumor growth by other mechanisms such as stimulating cytotoxic T-cell responses or by direct antitumor effects. Here we report results evaluating the properties of metronomic administration of an oral prodrug of gemcitabine LY2334737 in nontumor–bearing mice and in preclinical models of human ovarian (SKOV3-13) and breast cancer (LM2-4) xenografts. Through daily gavage (at 6 mg/kg/d), the schedules tested were devoid of toxicity and caused antitumor effects; however, a suppressive effect on CEPs was not detected. Unexpectedly, metronomic LY2334737 administration caused increased blood flow in luciferase-tagged LM2-4 tumor xenografts, and this effect, readily measured using contrast micro-ultrasound, coincided with a relative increase in tumor bioluminescence. These results highlight the possibility of significant antitumor effects mediated by metronomic administration of some chemotherapy drugs without a concomitant inhibition of systemic angiogenesis. Mol Cancer Ther; 11(3); 680–9. ©2011 AACR.
Fetal Intracardiac Potassium Chloride Injection to Expedite Second-Trimester Dilation and Evacuation
Authors: Singh Sareena , Seligman Neil S. , Jackson Brittany , Berghella Vincenzo
Published: December 2011

Objective: To determine whether potassium chloride (KCl)-induced feticide prior to termination by dilation and evacuation (D&E) improves surgical outcome. Methods: We conducted a retrospective study of women who underwent second-trimester (13 0/7 to 23 6/7 weeks) D&E at an urban university-based hospital between January 2000 and July 2010. Women were divided into 3 cohorts: (1) D&E for termination of pregnancy after feticide, (2) D&E without feticide, and (3) D&E for spontaneous pregnancy loss. We compared maternal characteristics, various perioperative variables, and surgical outcomes for all 3 groups. Anesthesia time was used as a surrogate for operative time in the primary outcome. Results: We analyzed 128 pregnancies (group 1: n = 23, group 2: n = 53, group 3: n = 52). Baseline maternal characteristics did not differ among the 3 groups. Anesthesia time was longest in the termination with KCl group (group 1: 116.9 min vs. group 2: 94.5 min and group 3: 90.3 min, p = 0.004), however, the effect was mitigated after controlling for fetal size (p = 0.176). There was no difference in blood loss (p = 0.968). Complications were uncommon, however, cervical lacerations were more common in the termination with KCl group (2 vs. 0 and 0, p = 0.010). Conclusion: Presurgical feticide with KCl was not associated with shorter anesthesia time. The decision to perform feticide should be based on other considerations, such as patient preference.
Changing Practice Patterns of Deep Brain Stimulation in Parkinson’s Disease and Essential Tremor in the USA
Authors: Pilitsis Julie G. , Burrows Anthony , Linton Peters Mary , Sargent Julie , Ng Sing Chau , Tseng Jennifer F.
Published: December 2011

Background: Randomized controlled studies have shown deep brain stimulation (DBS) to be an effective treatment for Parkinson’s disease (PD). Outside of large-center studies, little is known about trends in DBS use in the USA. Objectives: We employ the Nationwide Inpatient Sample to look at changes in DBS utilization over time. Methods: We identified all individuals with PD (332.0) and essential tremor (ET) (333.1) who underwent DBS (02.93) from 1998 to 2007. We examined demographics, hospital status, comorbidities, and in-hospital systemic/technical complications. DBS patients from 2000 and 2007 were compared using χ2 tests. Results: PD patients from the 2007 sample who underwent DBS were older (p = 0.01). Both ET and PD patients had significantly more comorbidities in 2007 (p < 0.001). In-hospital complications decreased from 3.8 to 2.8%. DBS was performed in medium- or high-volume centers in 70% of cases in 2000 and in 50% in 2007. In all groups, a majority of cases (range 65–71%) underwent DBS at hospitals in the western and southern USA. Conclusions: Patients who underwent DBS in the 2007 sample were older and had more comorbidities than those in the 2000 sample; in-hospital complications remained low. Understanding trends in DBS is helpful in assessing how the technology is adopted and what relationships should be further explored.
Beyond powerlessness
Authors: Mishra Pritipuspa
Published: December 2011

This article calls for a revision and expansion of our understanding of the concept of ‘vernacular’ in modern Indian scholarship. Current definitions of the concept pose it as a local, indigenous and powerless language. Scholars like Ranajit Guha and Partha Chatterjee have argued that such indegeneity and exclusion from structures of power provide vernacular languages with the capacity to represent the true voice of the oppressed. While this is true of vernacular languages in some instances, my analysis of linguistic politics in Orissa demonstrates that an overwhelming reliance on this definition of radical powerlessness blinds us to the hegemonic power exercised by regional vernacular languages in determining political and territorial alignments in modern India. This article illustrates how it is only by raising the question of how regional space is produced in India that we can illustrate the hegemonic power of major Indian vernacular languages.
Converging perspectives in audience studies and digital literacies: Youthful interpretations of an online genre
Authors: Das Ranjana
Published: December 2011

Engaging with a set of ideas proposed in an article published in this journal in 2004, this article transposes concepts from one mediated condition to another, as it applies selected theories from audience reception studies to research on media and digital literacies. In approaching multi-method qualitative data from a project that researched youthful digital literacies on social networking sites, the article presents a discussion on anticipations of genre and modes of interpretative engagement. It is concluded that the text–reader framework of audience reception studies pushes the digital literacies discussion away from treating literacies as practical skills, encouraging a critical examination of people’s interpretative engagement with media texts. By doing this, the article also explores how concepts lying at the core of the reception studies repertoire need to be retained and revised in the age of the internet.
Toward a deeper understanding of motion alternatives via an equivalence relation on local paths
Authors: Knepper Ross A , Srinivasa Siddhartha S , Mason Matthew T
Published: December 2011

Many problems in robot motion planning involve collision testing a set of local paths. In this paper we propose a novel solution to this problem by exploiting the structure of paths and the outcome of previous collision tests. Our approach circumvents expensive collision tests on a given path by detecting that the entire geometry of the path has effectively already been tested on a combination of other paths. We define a homotopy-like equivalence relation among local paths to detect this condition, and we provide algorithms that (1) classify paths based on equivalence, and (2) circumvent collision testing on up to 90% of them. We then prove both correctness and completeness of these algorithms and provide experimental results demonstrating a performance increase up to 300% in the rate of path tests. Additionally, we apply our equivalence relation to the navigation problem in a planning algorithm that takes advantage of information gained from equivalence relationships among collision-free paths. Finally, we explore applications of path equivalence to several other mechanisms, including kinematic chains and medical steerable needles.
Severe Hunter Syndrome (Mucopolysaccharidosis II) Phenotype Secondary to Large Deletion in the X Chromosome Encompassing IDS, FMR1, and AFF2 (FMR2)
Authors: Burruss Day M. , Wood Tim C. , Espinoza Lesby , Dwivedi Alka , Holden Kenton R.
Published: December 2011

A 2-year-old boy with an initial diagnosis of Hunter syndrome (mucopolysaccharidosis II) had a more severe phenotype than expected, which warranted further evaluation. The patient had severe infantile global neurodevelopmental delays, macrocephaly with a prominent forehead, coarse facial features with clear corneas, chronic congestion with snoring, wide-spaced teeth, short thick neck, hepatomegaly, an inguinal hernia repaired, early clawhand deformities, and severe generalized hypotonia. X chromosome microarray revealed a large deletion encompassing the genes IDS, FMR1, and AFF2 ( FMR2) confirming the diagnoses of both Hunter and fragile X syndromes. This case is also a reminder to clinicians that for optimum patient care, further diagnostic testing is warranted if there is concern that a patient’s phenotype is more severe or complex than would be expected for the initial neurogenetic diagnosis.
The Illusion of Statistical Control
Authors: Carlson Kevin D. , Wu Jinpei
Published: December 2011

The authors extend previous recommendations for improved control variable (CV) practice in management research by mapping the objectives for using statistical control to recommendations for research practice. Including CVs in research designs to permit statistical control of “nuisance” variance is a common research practice that is subject to well-documented and potentially serious problems. Yet because CVs are frequently weakly related to focal variables, they rarely influence the interpretation of results. As a result, current practice offers an illusion of statistical control when in fact little control actually occurs. The authors extend the growing literature on CV practice by examining the ambiguity of researchers' stated purposes for using statistical control that makes it difficult to determine whether common CV practice accomplishes any of these intents effectively. Guidelines for improving research practice are offered, including adopting a conservative stance toward the inclusion of CVs in the analysis of quasiexperimental and correlational designs guided by the principle “When in doubt, leave them out.”
Disclosure Antecedents in an Online Service Context
Authors: Mothersbaugh David L. , Foxx William K. , Beatty Sharon E. , Wang Sijun
Published: December 2011

The authors propose and find that the mixed results of prior research regarding disclosure antecedents are due in part to a failure to account for information sensitivity. Using prospect theory to examine willingness to disclose in an online service context, the authors propose and find that greater sensitivity of information requested produces weaker effects of customization benefits but stronger effects of information control and online privacy concern. The authors also find that customization benefits can overcome the negative effects of sensitive information requests when concern is lower or control is higher, and that perceived risk and firm trust are mechanisms through which disclosure antecedents operate. For theory, this research suggests that online disclosure models need to include sensitivity of information as a moderator. Moreover, the privacy paradox (consumers voice concerns but still disclose) may result from a failure to account for information sensitivity, since the authors find no effect of privacy concern on overall disclosure but find the predicted negative effect for higher sensitive information. For practice, our research suggests actionable strategies to aid online marketers in matching information requests with the needs and concerns of consumers by providing greater control and customization, enhancing firm trust, and adapting information requests to the situation.
Food insecurity among Australian children
Authors: Ramsey Rebecca , Giskes Katrina , Turrell Gavin , Gallegos Danielle
Published: December 2011

Children in food-insecure households may be at risk of poor health, developmental or behavioural problems. This study investigated the associations between food insecurity, potential determinants and health and developmental outcomes among children. Data on household food security, socio-demographic characteristics and children’s weight, health and behaviour were collected from households with children aged 3–17 years in socioeconomically disadvantaged suburbs by mail survey using proxy-parental reports (185 households). Data were analysed using logistic regression. Approximately one-in-three households (34%) were food insecure. Low household income was associated with an increased risk of food insecurity [odds ratio (OR), 16.20; 95% confidence interval (CI), 3.52–74.47]. Children with a parent born outside of Australia were less likely to experience food insecurity (OR, 0.42; 95% CI, 0.19–0.93). Children in food-insecure households were more likely to miss days from school or activities (OR, 3.52; 95% CI, 1.46–8.54) and were more likely to have borderline or atypical emotional symptoms (OR, 2.44; 95% CI, 1.11–5.38) or behavioural difficulties (OR, 2.35; 95% CI, 1.04–5.33). Food insecurity may be prevalent among socioeconomically disadvantaged households with children. The potential developmental consequences of food insecurity during childhood may result in serious adverse health and social implications.
The function of balance in US news coverage of uncontested issues: The case of female genital cutting
Authors: Wade Lisa
Published: December 2011

Most research on reporter practices examines coverage of contested topics. These require reporters to demonstrate objectivity by counterposing authoritative sources representing opposing sides. I examine news articles about a topic uncontested in the USA, female genital cutting (FGC), to complicate our understanding of how reporters do their job. In contrast to the literature, reporters strike a balance, including the ‘general public’ of FGC-practicing communities extensively. However, because the balance is confined to non-authoritative speakers ‘over there’, the balance nonetheless serves to stigmatize proponents. This research shows that the negative portrayal of members of FGC-practicing communities is due not only to their erasure in news coverage. Instead, whether standing translates into influence depends on context, something reporters can manipulate when there is consensus. Likewise, the separation of topics into contested and uncontested erases the ways in which controversy is not a characteristic of issues, but a function of reporter decisions.
Bayesian first order auto-regressive latent variable models for multiple binary sequences
Authors: Giardina Federica , Guglielmi Alessandra , Quintana Fernando A , Ruggeri Fabrizio
Published: December 2011

Longitudinal clinical trials often collect long sequences of binary data monitoring a disease process over time. Our application is a medical study conducted in the US by the Veterans Administration Cooperative Urological Research Group to assess the effectiveness of a chemotherapy treatment (thiotepa) in preventing recurrence on subjects affected by bladder cancer. We propose a generalized linear model with latent auto-regressive structure for longitudinal binary data following a Bayesian approach. We discuss inference as well as sensitivity to prior choices for the bladder cancer data. We find that there is a significant treatment effect in the sense that treated patients have much smaller predicted recurrence probabilities than placebo patients.
Hierarchical mixture models for biclustering in microarray data
Authors: Martella F , Alfò M , Vichi M
Published: December 2011

In the last few years, model-based clustering techniques have become widely used in the context of microarray data analysis. In this empirical context, a potential purpose for statistical approaches is the identification of clusters of genes that are co-expressed under subsets of experimental conditions. We discuss a hierarchical mixture model to combine advantages of allowing for dependence within gene clusters and for simultaneous clustering of genes and experimental conditions. Thanks to the adopted hierarchical structure, we may distinguish gene clusters from mixture components, where the latter may represent intra-cluster gene-specific extra-Gaussian departures. To cluster experimental conditions, instead, we suggest a suitable parameterization of component-specific means by using a binary row stochastic matrix representing condition membership. The performance of the proposed approach is discussed on both simulated and real datasets.
A flexible instrumental variable approach
Authors: Marra Giampiero , Radice Rosalba
Published: December 2011

Classical regression model literature has generally assumed that measured and unmeasured covariates are statistically independent. For many applications, this assumption is clearly tenuous. When unobservables are associated with included regressors and have an impact on the response, standard estimation methods will not be valid. This means that estimation results from observational studies, whose aim is to evaluate the impact of a treatment of interest on a response variable, will be biased and inconsistent in the presence of unmeasured confounders. One method for obtaining consistent estimates of treatment effects when dealing with linear models is the instrumental variable (IV) approach. Linear models have been extended to generalized linear models (GLMs) and generalized additive models (GAMs), and although IV methods have been proposed to deal with GLMs, fitting methods to carry out IV analysis within the GAM context have not been developed. We propose a simple but effective two-stage procedure for IV estimation when dealing with GAMs represented using any penalized regression spline approach and a correction procedure for confidence intervals. We explain under which conditions the proposed method works and illustrate its empirical validity through an extensive simulation experiment and a health study where unmeasured confounding is suspected to be present.
Can the vector space model be used to identify biological entity activities?
Authors: Maciel Wesley D , Faria-Campos Alessandra C , Gonçalves Marcos A , Campos Sérgio VA
Published: December 2011

Background

Biological systems are commonly described as networks of entity interactions. Some interactions are already known and integrate the current knowledge in life sciences. Others remain unknown for long periods of time and are frequently discovered by chance. In this work we present a model to predict these unknown interactions from a textual collection using the vector space model (VSM), a well known and established information retrieval model. We have extended the VSM ability to retrieve information using a transitive closure approach. Our objective is to use the VSM to identify the known interactions from the literature and construct a network. Based on interactions established in the network our model applies the transitive closure in order to predict and rank new interactions.

Results

We have tested and validated our model using a collection of patent claims issued from 1976 to 2005. From 266,528 possible interactions in our network, the model identified 1,027 known interactions and predicted 3,195 new interactions. Iterating the model according to patent issue dates, interactions found in a given past year were often confirmed by patent claims not in the collection and issued in more recent years. Most confirmation patent claims were found at the top 100 new interactions obtained from each subnetwork. We have also found papers on the Web which confirm new inferred interactions. For instance, the best new interaction inferred by our model relates the interaction between the adrenaline neurotransmitter and the androgen receptor gene. We have found a paper that reports the partial dependence of the antiapoptotic effect of adrenaline on androgen receptor.

Conclusions

The VSM extended with a transitive closure approach provides a good way to identify biological interactions from textual collections. Specifically for the context of literature-based discovery, the extended VSM contributes to identify and rank relevant new interactions even if these interactions occcur in only a few documents in the collection. Consequently, we have developed an efficient method for extracting and restricting the best potential results to consider as new advances in life sciences, even when indications of these results are not easily observed from a mass of documents.
Modeling and analysis of cell membrane systems with probabilistic model checking
Authors: Crepalde Mirlaine A , Faria-Campos Alessandra C , Campos Sérgio VA
Published: December 2011

Background

Recently there has been a growing interest in the application of Probabilistic Model Checking (PMC) for the formal specification of biological systems. PMC is able to exhaustively explore all states of a stochastic model and can provide valuable insight into its behavior which are more difficult to see using only traditional methods for system analysis such as deterministic and stochastic simulation. In this work we propose a stochastic modeling for the description and analysis of sodium-potassium exchange pump. The sodium-potassium pump is a membrane transport system presents in all animal cell and capable of moving sodium and potassium ions against their concentration gradient.

Results

We present a quantitative formal specification of the pump mechanism in the PRISM language, taking into consideration a discrete chemistry approach and the Law of Mass Action aspects. We also present an analysis of the system using quantitative properties in order to verify the pump reversibility and understand the pump behavior using trend labels for the transition rates of the pump reactions.

Conclusions

Probabilistic model checking can be used along with other well established approaches such as simulation and differential equations to better understand pump behavior. Using PMC we can determine if specific events happen such as the potassium outside the cell ends in all model traces. We can also have a more detailed perspective on its behavior such as determining its reversibility and why its normal operation becomes slow over time. This knowledge can be used to direct experimental research and make it more efficient, leading to faster and more accurate scientific discoveries.
Improvement in the prediction of the translation initiation site through balancing methods, inclusion of acquired knowledge and addition of features to sequences of mRNA
Authors: Silva Lívia Márcia , de Souza Teixeira Felipe Carvalho , Ortega José Miguel , Zárate Luis Enrique , Nobre Cristiane Neri
Published: December 2011

Background

The accurate prediction of the initiation of translation in sequences of mRNA is an important activity for genome annotation. However, obtaining an accurate prediction is not always a simple task and can be modeled as a problem of classification between positive sequences (protein codifiers) and negative sequences (non-codifiers). The problem is highly imbalanced because each molecule of mRNA has a unique translation initiation site and various others that are not initiators. Therefore, this study focuses on the problem from the perspective of balancing classes and we present an undersampling balancing method, M-clus, which is based on clustering. The method also adds features to sequences and improves the performance of the classifier through the inclusion of knowledge obtained by the model, called InAKnow.

Results

Through this methodology, the measures of performance used (accuracy, sensitivity, specificity and adjusted accuracy) are greater than 93% for the Mus musculus and Rattus norvegicus organisms, and varied between 72.97% and 97.43% for the other organisms evaluated: Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Nasonia vitripennis. The precision increases significantly by 39% and 22.9% for Mus musculus and Rattus norvegicus, respectively, when the knowledge obtained by the model is included. For the other organisms, the precision increases by between 37.10% and 59.49%. The inclusion of certain features during training, for example, the presence of ATG in the upstream region of the Translation Initiation Site, improves the rate of sensitivity by approximately 7%. Using the M-Clus balancing method generates a significant increase in the rate of sensitivity from 51.39% to 91.55% (Mus musculus) and from 47.45% to 88.09% (Rattus norvegicus).

Conclusions

In order to solve the problem of TIS prediction, the results indicate that the methodology proposed in this work is adequate, particularly when using the concept of acquired knowledge which increased the accuracy in all databases evaluated.
Obesity management and continuing medical education in primary care: results of a Swiss survey
Authors: Huber Carola A , Mohler-Kuo Meichun , Zellweger Ueli , Zoller Marco , Rosemann Thomas , Senn Oliver
Published: December 2011

Background

The worldwide increase in obesity is becoming a major health concern. General practitioners (GPs) play a central role in managing obesity. We aimed to examine Swiss GPs self-reported practice in diagnosis and treatment of obesity with a special focus on the performance of waist measurement.

Methods

A structured self-reported questionnaire was mailed to 323 GPs recruited from four urban physician networks in Switzerland. Measures included professional experience, type of practice, obesity-related continuing medical education (CME) and practice in dealing with obesity such as waist measurement. We assessed the association between the performance of waist measurement and obesity-related CME by multivariate ordered logistic regression controlling for GP characteristics as potential confounders.

Results

A total of 187 GPs responded to the questionnaire. More than half of the GPs felt confident in managing obesity. The majority of the GPs (73%) spent less than 4 days in the last 5 years on obesity-related CME. More than half of GPs gave advice to reduce energy intakes (64%), intakes of high caloric and alcoholic drinks (56%) and to increase the physical activity (78%). Half of the GPs seldom performed waist measurement and documentation. The frequency of obesity-related CME was independently associated with the performance of waist measurement when controlled for GPs' characteristics by multivariate ordered logistic regression.

Conclusions

The majority of GPs followed guideline recommendations promoting physical activity and dietary counselling. We observed a gap between the increasing evidence for waist circumference assessment as an important measure in obesity management and actual clinical practice. Our data indicated that specific obesity-related CME might help to reduce this gap.
Comparison of resource use by COPD patients on inhaled therapies with long-acting bronchodilators: a database study
Authors: Kozma Chris M , Paris Andrew L , Plauschinat Craig A , Slaton Terra , Mackowiak John I
Published: December 2011

Background

The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA) OR long-acting muscarinic antagonist (LAMA); LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS) prescription claims.

Methods

This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database. Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium), LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol), and LABA, LAMA and ICS (bronchodilators plus steroid) groups. Post-period comparisons were evaluated with analysis of covariance. Costs were evaluated from a commercial payer perspective.

Results

A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure). Post-match assessments indicated balance among the cohorts. COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA $2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p < .0001) with the differences driven by study medication costs. However, non-study COPD medication costs were higher for the LABA or LAMA therapy group ($911 SE = 91) compared to the LABA and LAMA therapy group ($668 SE = 58; p = 0.0238) and non-study respiratory medications were approximately $100 greater for the LABA or LAMA therapy group relative to both LABA and LAMA (p = .0018) and LABA, LAMA, and ICS (p = .0071) therapy groups. While there was no observed difference in outpatient costs, there was a slightly higher number of outpatient visits per patient in the LABA and LAMA (25.5 SE = 0.9, p = 0.0070) relative to the LABA or LAMA therapy group (22.3 SE = 0.8) and higher utilization (89.7% of patients) with COPD visits in the LABA and LAMA therapy group relative to both the LABA or LAMA (73.8%; p < .0001) and LABA, LAMA and ICS therapy groups (85.3; p = 0.0305).

Conclusions

Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies. A COPD-related cost offset was observed from single bronchodilator to two bronchodilators. Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators.
Bovine pericardium retail preserved in glutaraldehyde and used as a vascular patch
Authors: Saporito Wladimir F , Pires Adílson C , Cardoso Sérgio H , Correa João A , de Abreu Luiz Carlos , Valenti Vitor E , Miller Luciano MR , Colombari Eduardo
Published: December 2011

Background

In this study we evaluated the performance of bovine pericardium preserved in glutaraldehyde used as a vascular patch.

Methods

Fourteen young pigs, six females and eight males, weighting 10.3 - 18.4 kg were used in our study. We implanted three remnants in each pig, two in the abdominal aorta and one was juxtaposed to the peritoneum. The smooth face (SF) and rough face (RF) of each remnant were implanted turned to the vessel inner portion and one remnant was juxtaposed to the peritoneum. The animals were sacrificed in 4.5 - 8 months after surgery (75 - 109 kg). The remnants were assessed for aorta wall, fibroses formation in inner apposition and calcification related to the face turned to the vessel inner portion.

Results

The rough face showed a lower dilatation level compared to the face implanted in adjacent aorta. There was no difference between intensity and/or incidence of graft calcification when the superficies were compared. The bovine pericardium preserved in glutaraldehyde did not show alterations in its structure when implanted with different faces turned to the inner portion of vessel.

Conclusion

When turned to the inner portion of the vessel, the rough face of the remnant presented a lower dilatation in relation to the adjacent aorta and a better quality of endothelium layer and did not show a difference between intensity and/or incidence of graft calcification.
Molecular preservation by extraction and fixation, mPREF: a method for small molecule biomarker analysis and histology on exactly the same tissue
Authors: Shuster Jeffrey R , Lance Raymond S , Troyer Dean A
Published: December 2011

Background

Histopathology is the standard method for cancer diagnosis and grading to assess aggressiveness in clinical biopsies. Molecular biomarkers have also been described that are associated with cancer aggressiveness, however, the portion of tissue analyzed is often processed in a manner that is destructive to the tissue. We present here a new method for performing analysis of small molecule biomarkers and histology in exactly the same biopsy tissue.

Methods

Prostate needle biopsies were taken from surgical prostatectomy specimens and first fixed, each in a separate vial, in 2.5 ml of 80% methanol:water. The biopsies were fixed for 24 hrs at room temperature and then removed and post-processed using a non-formalin-based fixative (UMFIX), embedded, and analyzed by hematoxylin and eosin (H&E) and by immunohistochemical (IHC) staining. The retained alcohol pre-fixative was analyzed for small molecule biomarkers by mass spectrometry.

Results

H&E analysis was successful following the pre-fixation in 80% methanol. The presence or absence of tumor could be readily determined for all 96 biopsies analyzed. A subset of biopsy sections was analyzed by IHC, and cancerous and non-cancerous regions could be readily visualized by PIN4 staining. To demonstrate the suitability for analysis of small molecule biomarkers, 28 of the alcohol extracts were analyzed using a mass spectrometry-based metabolomics platform. All extracts tested yielded successful metabolite profiles. 260 named biochemical compounds were detected in the alcohol extracts. A comparison of the relative levels of compounds in cancer containing vs. non-cancer containing biopsies showed differences for 83 of the compounds. A comparison of the results with prior published reports showed good agreement between the current method and prior reported biomarker discovery methods that involve tissue destructive methods.

Conclusions

The Molecular Preservation by Extraction and Fixation (mPREF) method allows for the analysis of small molecule biomarkers from exactly the same tissue that is processed for histopathology.