bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple sclerosis in diverse populations: characteristics in distinct Arab ethnicities in Israel
Authors: Siegel Michal , Paperna Tamar , Lejbkowicz Izabella , Petrou Panayiota , Shahien Radi , Karussis Dimitrios , Lavi Idit , Dishon Sara , Rawashdeh Hanna , Miller Ariel 
Published: May 2012

Background: Multiple sclerosis (MS) prevalence and genetic susceptibility varies among the different ethnic groups of Jews and Arabs in Israel. Objective: Characterization of MS disease course in Christian, Muslim and Druze Arabs in Israel. Methods: Historical cohort and three-year follow-up cohort analyses based on interviews and clinical charts of 149 Arab MS patients (78 Muslims, 49 Christians and 22 Druze) from three MS centers in Israel. Significant findings were adjusted for use of disease modifying therapy. Results: Age of onset (means between 30 and 31 years) and incomplete recovery rates after the first relapse (~50%) were similar for Christian, Muslim and Druze patients. Low rates of primary progressive MS (≤1%) were observed. Differences between the ethnicities in the time from onset to the second neurological episode were observed among females, but not males. Druze and Muslim women were more likely to have a second event within two years from the first event compared with Christians (odds ratios =8.8, p= 0.02; odds ratio=6.6, p=0.007 respectively). Trends for higher annual relapse rates, annual disability progression rates and MS Severity Scores were observed among the Druze. Conclusions: Among the Israeli Arab female MS patients, Druze and Muslims exhibit a more rapid disease course in comparison with Christians. Further elucidation of population-specific MS phenotypes may contribute to improved disease management.
Natalizumab strongly suppresses cortical pathology in relapsing–remitting multiple sclerosis
Authors: Rinaldi F , Calabrese M , Seppi D , Puthenparampil M , Perini P , Gallo P 
Published: May 2012

Background: Since cortical pathology has been indicated to play a relevant role in the physical and cognitive disability of multiple sclerosis (MS) patients, this study aims to analyze the efficacy of natalizumab in slowing down its progression. Methods: A total of 120 relapsing–remitting MS patients completed a 2-year prospective study: 35 received natalizumab, 50 received interferon beta-1a or glatiramer acetate (immunomodulatory agents - IMA) and 35 remained untreated. Forty healthy subjects constituted the reference population. Clinical and magnetic resonance imaging (MRI) evaluations (including cortical lesions and atrophy) were performed at baseline and after 2 years. Results: Natalizumab significantly reduced accumulation of new cortical lesions (0.2±0.6,range 0–3) compared to immunomodulatory agents (1.3±1.1 togli spazio, range 1–6, p=0.001) and no treatment (2.9±1.5, range 1–8, p<0.001). The percentage of patients with new cortical lesions was also lower in natalizumab-treated patients (20%) compared to IMA-treated and untreated patients (68.0% and 74.2%; p<0.001 for both comparisons). Furthermore, the progression of cortical atrophy was significantly reduced by natalizumab (% change=1.7%) compared to IMA (3.7%, p=0.003) and no therapy (4.6%, p<0.001). Finally, a greater percentage (51.4%) of natalizumab-treated patients remained disease-free (no clinical or MRI evidence of disease activity or progression) compared to IMA-treated (18%, p=0.001) and untreated patients (5.7%, p<0.001). Conclusions: Natalizumab treatment significantly decreases cortical lesion accumulation and cortical atrophy progression in severe relapsing–remitting MS. While supporting the inflammatory origin of cortical lesions, our results highlight the significant impact of natalizumab on cortical pathology.
Heapviz: Interactive heap visualization for program understanding and debugging
Authors: Kelley Sean , Aftandilian Edward , Gramazio Connor , Ricci Nathan , Su Sara L. , Guyer Samuel Z. 
Published: May 2012

Understanding the data structures in a program is crucial to understanding how the program works, or why it does not work. Inspecting the code that implements the data structures, however, is an arduous task and often fails to yield insights into the global organization of a program’s data. Inspecting the actual contents of the heap solves these problems but presents a significant challenge of its own: finding an effective way to present the enormous number of objects it contains. In this paper we present Heapviz, a tool for visualizing and exploring snapshots of the heap obtained from a running Java program. Unlike existing tools, such as traditional debuggers, Heapviz presents a global view of the program state as a graph, together with powerful interactive capabilities for navigating it. Our tool employs several key techniques that help manage the scale of the data. First, we reduce the size and complexity of the graph by using algorithms inspired by static shape analysis to aggregate the nodes that make up a data structure. Second, we implement a powerful visualization component whose interactive interface provides extensive support for exploring the graph. The user can search for objects based on type, connectivity, and field values; group objects; and color or hide and show each group. The user may also inspect individual objects to see their field values and neighbors in the graph. These interactive abilities help the user manage the complexity of these huge graphs. By applying Heapviz to both constructed and real-world examples, we show that it provides programmers with a powerful and intuitive tool for exploring program behavior.
Taking the long view: how to design a series of Phase III trials to maximize cumulative therapeutic benefit
Authors: Deley Marie-Cécile Le , Ballman Karla V , Marandet Julien , Sargent Daniel 
Published: May 2012

Background Traditional clinical trial designs strive to definitively establish the superiority of an experimental treatment, which results in risk-adverse criteria and large sample sizes. Increasingly, common cancers are recognized as consisting of small subsets with specific aberrations for targeted therapy, making large trials infeasible. Purpose To compare the performance of different trial design strategies over a long-term research horizon. Methods We simulated a series of two-treatment superiority trials over 15 years using different design parameters. Trial parameters examined included the number of positive trials to establish superiority (one-trial vs. two-trial rule), α level (2.5%–50%), and the number of trials in the 15-year period, K (thus, trial sample size). The design parameters were evaluated for different disease scenarios, accrual rates, and distributions of treatment effect. Metrics used included the overall survival gain at a 15-year horizon measured by the hazard ratio (HR), year 15 versus year 0. We also computed the expected total survival benefit and the risk of selecting as new standard of care at year 15 a treatment inferior to the initial control treatment, P(detrimental effect). Results Expected survival benefits over the 15-year horizon were maximized when more (smaller) trials were conducted than recommended under traditional criteria, using the criterion of one positive trial (vs. two), and relaxing the α value from 2.5% to 20%. Reducing the sample size and relaxing the α value also increased the likelihood of selecting an inferior treatment at the end. The impact of α and K on the survival benefit depended on the specific disease scenario and accrual rate: greater gains for relaxing α in diseases with good outcome and/or low accrual rates and greater gains for increasing K for diseases with poor outcomes. Trials with smaller sample size did not perform well when using stringent (standard) level of evidence. For each disease scenario and accrual rate studied, the optimal design, defined as the design that the maximized expected total survival benefit while constraining P(detrimental effect) < 2.5%, specified α = 20% or 10%, and a sample size considerably smaller than that recommended by the traditional designs. The results were consistent under different assumed distributions for treatment effect. Limitations The simulations assumed no toxicity issues and did not consider interim analyses. Conclusions It is worthwhile to consider a design paradigm that seeks to maximize the expected survival benefit across a series of trials, over a longer research horizon. In today’s environment of constrained, biomarker-selected populations, our results indicate that smaller sample sizes and larger α values lead to greater long-term survival gains compared to traditional large trials designed to meet stringent criteria with a low efficacy bar.
Clinical and microbiologic characteristics of tcdA-negative variant clostridium difficile infections
Authors: Kim Jieun , Pai Hyunjoo , Seo Mi-ran , Kang Jung Oak 
Published: May 2012

Abstract

Background
The tcdA-negative variant (A-B+) of Clostridium difficile is prevalent in East Asian countries. However, the risk factors and clinical characteristics of A-B+
C. difficile infections (CDI) are not clearly documented. The objective of this study was to investigate these characteristics.

Methods
From September 2008 through January 2010, the clinical characteristics, medication history and treatment outcomes of CDI patients were recorded prospectively. Toxin characterization and antibiotic susceptibility tests were performed on stool isolates of C. difficile.

Results
During the study period, we identified 22 cases of CDI caused by tcdA-negative tcdB-positive (A-B+) strains and 105 cases caused by tcdA-positive tcdB-positive (A+B+) strains. There was no significant difference in disease severity or clinical characteristics between the two groups. Previous use of clindamycin and young age were identified as significant risk factors for the acquisition of A-B+ CDI (OR = 4.738, 95% CI 1.48–15.157, p = 0.009 and OR = 0.966, 95% CI 0.935–0.998, p = 0.038, respectively) in logistic regression.
Rates of resistance to clindamycin were 100% and 69.6% in the A-B+ and A+B+ isolates, respectively (p = 0.006), and the ermB gene was identified in 17 of 21 A-B+ isolates (81%). Resistance to moxifloxacin was also more frequent in the A-B+ than in the A+B+ isolates (95.2% vs. 63.7%, p = 0.004).

Conclusions
The clinical course of A-B+ CDI is not different from that of A+B+ CDI. Clindamycin use is a significant risk factor for the acquisition of tcdA-negative variant strains.
A pragmatic assessment of the relative efficiency of outreach chlamydia screening events conducted in non-clinical settings
Authors: Bowden Francis J , Currie Marian J , Todkill Muareen , Schmidt Mathias , Webeck Sue , Del Rosario Rendry , Bavinton Tim , Tyson Alexandra 
Published: May 2012

Abstract

Background
Opportunistic screening for chlamydia in non-clinical settings is becoming more common, but little is known about which settings (or events) offer the best return on investment. We measured the relative efficiency of each screening site and event during the conduct of a chlamydia education and screening outreach program which used a cash incentive to encourage participation (SOC2).

Methods
SOC2 staff identified sites and organised events in non-clinical sites where young people were likely to congregate. 16 to 30 years olds were offered chlamydia education and a cash reward of AUD10 if they chose to be screened for chlamydia. Data collected during these activities were used to calculated five measures of efficiency: i) screening yield’ (proportion of people providing a sample), ii) proportion of positive tests, iii) ‘event screening tempo’ (number of screens performed for every hour that screening is offered), iv) ‘staff hour screening tempo’ (number of screens performed per hour of staff time) and v) ‘chlamydia detection tempo’ (number of positive tests detected per hour of screening).

Results
3011 people (71% male) were screened during 18 events at 10 venues. Overall ‘screening yield’ was 43.8% (range: 20–77%) and 1.7% (95% CI: 1.1–3.0) of tests were positive (by event range 1–3%). Overall, the ‘event screening tempo’ was 23.7 screens per event hour (range 8.0–79.0), the ‘staff hour screening tempo’ was 6.5 screens per staff hour and the ‘chlamydia detection tempo’ was 0.4 positive tests per hour (range: 0–1.75).

Conclusion
Assessing the efficiency of screening sites and programs should be integral to their conduct. We suggest the use of five measures to enable pragmatic assessment of any screening program. We introduce the terms ‘event screening tempo’, ‘staff hour screening tempo’ and ‘chlamydia detection tempo’ to describe three of these simple measures.
Multi-layer topology control for long-term wireless sensor networks
Authors: Yoon Ikjune , Noh Dong Kun , Shin Heonshik 
Published: May 2012

Abstract
Due to the inefficiency of a flat topology, most wireless sensor networks (WSNs) have a cluster or tree structure; but this causes an imbalance of residual energy between nodes, which gets worse over time as nodes become defunct and replacements are inserted. Multiple layers are better then the typical two-layer cluster-based topology, because it can better accommodate nodes with different levels of residual energy. We propose that each node should periodically determine its own layer, as its situation and the network topology changes. We introduce a topology control scheme for long-term WSNs with these features. Simulations show that this scheme can balance node energy levels, and thus extend network lifetime.
Coupled and tripled coincidence point results without compatibility
Authors: Hussain Nawab , Latif Abdul , Shah Masood Hussain 
Published: May 2012

Abstract
In this article, we introduce a new and simple approach to coupled and tripled coincidence point theory. By using our method, we establish coupled coincidence point results of Lakshmikantham and Ćirić, Binayak et al., Alotaibi and Alsulami without any type of commutativity condition on F and g. We also use our technique to prove tripled coincidence point results of Borcut and Berinde without commutativity of maps. Also, we give a supporting example of non-commuting, non-compatible mappings where the above mentioned results can not be applied.

Mathematics Subject Classification: Primary, 47H10; Secondary, 54H25; 34B15.
Substrate utilization during submaximal exercise in children with a severely obese parent
Authors: Eaves Audrey D , Colon Ashley , DuBose Katrina D , Collier David , Houmard Joseph A 
Published: May 2012

Abstract

Background
We have reported a reduction in fatty acid oxidation (FAO) at the whole-body level and in skeletal muscle in severely obese (BMI ≥ 40 kg/m2) individuals; this defect is retained in cell culture suggesting an inherent component. The purpose of the current study was to determine if an impairment in whole-body fatty acid oxidation (FAO) was also evident in children with a severely obese parent.

Methods
Substrate utilization during submaximal exercise (cycle ergometer) was determined in children ages 8–12 y with a severely obese parent (OP, n = 13) or two lean/non-obese (BMI range of 18 to 28 kg/m2) parents (LP, n = 13). A subgroup of subjects (n = 3/group) performed 4 weeks of exercise training with substrate utilization measured after the intervention.

Results
The children did not differ in age (LP vs. OP, respectively) (10.7 ± 0.5 vs. 10.2 ± 0.5 y), BMI percentile (65.3 ± 5.2 vs. 75.9 ± 7), Tanner Stage (1.4 ± 0.2 vs. 1.5 ± 0.2), VO2peak (40.3 ± 2.7 vs. 35.6 ± 2.6 ml/kg/min) or physical activity levels (accelerometer). At the same absolute workload of 15 W (~38% VO2peak), RER was significantly (P ≤ 0.05) lower in LP vs. OP (0.83 ± 0.02 vs. 0.87 ± 0.01) which was reflected in a reduced reliance on FAO for energy production in the OP group (58.6 ± 5.1 vs. 43.1 ± 4.0% of energy needs during exercise from FAO). At a higher exercise intensity (~65% VO2peak) there were no differences in substrate utilization between LP and OP. After exercise training RER tended to decrease (P = 0.06) at the 15 W workload, suggesting an increased reliance on FAO regardless of group.

Conclusions
These findings suggest that the decrement in FAO with severe obesity has an inherent component that may be overcome with exercise training.
Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP Kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages
Authors: Lee Jong Kwon , Sayers Brian C , Chun Kyung-Soo , Lao Huei-Chen , Shipley-Phillips Jeanette K , Bonner James C , Langenbach Robert 
Published: May 2012

Abstract

Background
Carbon nanotubes (CNTs) are engineered graphene cylinders with numerous applications in engineering, electronics and medicine. However, CNTs cause inflammation and fibrosis in the rodent lung, suggesting a potential human health risk. We hypothesized that multi-walled CNTs (MWCNTs) induce two key inflammatory enzymes in macrophages, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), through activation of extracellular signal-regulated kinases (ERK1,2).

Methods
RAW264.7 macrophages were exposed to MWCNTs or carbon black nanoparticles (CBNPs) over a range of doses and time course. Uptake and subcellular localization of MWCNTs was visualized by transmission electron microscopy (TEM). Protein levels of COX-2, iNOS, and ERK1,2 (total ERK and phosphorylated ERK) were measured by Western blot analysis. Prostaglandin-E2 (PGE2) and nitric oxide (NO) levels in cell supernatants were measured by ELISA and Greiss assay, respectively.

Results
MWCNTs, but not CBNPs, induced COX-2 and iNOS in a time- and dose-dependent manner. COX-2 and iNOS induction by MWCNTs correlated with increased PGE2 and NO production, respectively. MWCNTs caused ERK1,2 activation and inhibition of ERK1,2 (U0126) blocked MWCNT induction of COX-2 and PGE2 production, but did not reduce the induction of iNOS. Inhibition of iNOS (L-NAME) did not affect ERK1,2 activation, nor did L-NAME significantly decrease COX-2 induction by MWCNT. Nickel nanoparticles (NiNPs), which are present in MWCNTs as a residual catalyst, also induced COX-2 via ERK-1,2. However, a comparison of COX-2 induction by MWCNTs containing 4.5 and 1.8% Ni did not show a significant difference in ability to induce COX-2, indicating that characteristics of MWCNTs in addition to Ni content contribute to COX-2 induction.

Conclusion
This study identifies COX-2 and subsequent PGE2 production, along with iNOS induction and NO production, as inflammatory mediators involved in the macrophage response to MWCNTs. Furthermore, our work demonstrates that COX-2 induction by MWCNTs in RAW264.7 macrophages is ERK1,2-dependent, while iNOS induction by MWCNTs is ERK1,2-independent. Our data also suggest contributory physicochemical factors other than residual Ni catalyst play a role in COX-2 induction to MWCNT.
The Arabidopsis thaliana-Alternaria brassicicola pathosystem: A model interaction for investigating seed transmission of necrotrophic fungi
Authors: Pochon Stephanie , Terrasson Emmanuel , Guillemette Thomas , Iacomi-Vasilescu Beatrice , Georgeault Sonia , Juchaux Marjorie , Berruyer Romain , Debeaujon Isabelle , Simoneau Philippe , Campion Claire 
Published: May 2012

Abstract

Background
Seed transmission constitutes a major component of the parasitic cycle for several fungal pathogens. However, very little is known concerning fungal or plant genetic factors that impact seed transmission and mechanisms underlying this key biological trait have yet to be clarified. Such lack of available data could be probably explained by the absence of suitable model pathosystem to study plant-fungus interactions during the plant reproductive phase.

Results
Here we report on setting up a new pathosystem that could facilitate the study of fungal seed transmission. Reproductive organs of Arabidopsis thaliana were inoculated with Alternaria brassicicola conidia. Parameters (floral vs fruit route, seed collection date, plant and silique developmental stages) that could influence the seed transmission efficiency were tested to define optimal seed infection conditions. Microscopic observations revealed that the fungus penetrates siliques through cellular junctions, replum and stomata, and into seed coats either directly or through cracks. The ability of the osmosensitive fungal mutant nik1Δ3 to transmit to A. thaliana seeds was analyzed. A significant decrease in seed transmission rate was observed compared to the wild-type parental strain, confirming that a functional osmoregulation pathway is required for efficient seed transmission of the fungus. Similarly, to test the role of flavonoids in seed coat protection against pathogens, a transparent testa Arabidopsis mutant (tt4-1) not producing any flavonoid was used as host plant. Unexpectedly, tt4-1 seeds were infected to a significantly lower extent than wild-type seeds, possibly due to over-accumulation of other antimicrobial metabolites.

Conclusions
The Arabidopsis thaliana-Alternaria brassicicola pathosystem, that have been widely used to study plant-pathogen interactions during the vegetative phase, also proved to constitute a suitable model pathosystem for detailed analysis of plant-pathogen interactions during the reproductive phase. We demonstrated that it provides an excellent system for investigating the impact of different fungal or plant mutations on the seed transmission process and therefore paves the way towards future high-throughput screening of both Arabidopsis and fungal mutant.
Translating research into practice in Leeds and Bradford (TRiPLaB): a protocol for a programme of research
Authors: Hanbury Andria , Thompson Carl , Wilson Paul M , Farley Kate , Chambers Duncan , Warren Erica , Bibby John , Mannion Russell , Watt Ian S , Gilbody Simon 
Published: May 2012

Abstract

Background
The National Institute for Health Research (NIHR) has funded nine Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). Each CLAHRC is a partnership between higher education institutions (HEIs) and the NHS in nine UK regional health economies. The CLAHRC for Leeds, York, and Bradford comprises two 'research themes' and three 'implementation themes.' One of these implementation themes is Translating Research into Practice in Leeds and Bradford (TRiPLaB). TRiPLaB aims to develop, implement, and evaluate methods for inducing and sustaining the uptake of research knowledge into practice in order to improve the quality of health services for the people of Leeds and Bradford.

Methods
TRiPLaB is built around a three-stage, sequential, approach using separate, longitudinal case studies conducted with collaborating NHS organisations, TRiPLaB will select robust innovations to implement, conduct a theory-informed exploration of the local context using a variety of data collection and analytic methods, and synthesise the information collected to identify the key factors influencing the uptake and adoption of targeted innovations. This synthesis will inform the development of tailored, multifaceted, interventions designed to increase the translation of research findings into practice. Mixed research methods, including time series analysis, quasi-experimental comparison, and qualitative process evaluation, will be used to evaluate the impact of the implementation strategies deployed.

Conclusion
TRiPLaB is a theory-informed, systematic, mixed methods approach to developing and evaluating tailored implementation strategies aimed at increasing the translation of research-based findings into practice in one UK health economy. Through active collaboration with its local NHS, TRiPLaB aims to improve the quality of health services for the people of Leeds and Bradford and to contribute to research knowledge regarding the interaction between context and adoption behaviour in health services.