bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel p38α Mitogen‐Activated Protein Kinase Inhibitor Shows Analgesic Efficacy in Acute Postsurgical Dental Pain
Authors: Tong Sandra E. , Daniels Stephen E. , Black Peter , Chang Stephen , Protter Andrew , Desjardins Paul J.
Published: June 2011

SCIO‐469 is a selective p38α mitogen‐activated protein kinase (MAPK) inhibitor for preclinical models of acute pain. This prospective, double‐blind, randomized clinical study compared efficacy and safety of oral SCIO‐469, ibuprofen, and placebo in postsurgical dental pain. Subjects (n = 263) undergoing extraction of 1 or more impacted mandibular third molars received preoperative treatment with SCIO‐469 (150, 210, or 300 mg), ibuprofen (400 mg), or placebo; the 210‐mg group received 90 mg postoperatively. A 4‐point categorical scale and a 100‐mm visual analogue scale were used to measure pain intensity. The primary end point was median time from first incision to first rescue medication using the Kaplan‐Meier product limit estimator. All SCIO‐469 groups had significantly longer times to rescue medication compared with placebo; preoperative and postoperative treatment with 210 + 90 mg SCIO‐469 resulted in 8.1 hours versus 4.1 hours to rescue for placebo (P = .003). Ibuprofen also increased time to rescue medication (6.6 hours) versus placebo (P = .04). Dizziness, headache, and nausea were the most frequently reported adverse events. This is the first clinical demonstration of antinociceptive effects in acute pain with preoperative administration of a p38α MAPK inhibitor.
An Improved Model for Disease Progression in Patients From the Alzheimer's Disease Neuroimaging Initiative
Authors: Samtani Mahesh N. , Farnum Michael , Lobanov Victor , Yang Eric , Raghavan Nandini , DiBernardo Allitia , Narayan Vaibhav ,   And the Alzheimer's Disease Neuroimaging Initiative
Published: June 2011

The objective of this analysis was to develop a semi‐mechanistic nonlinear disease progression model using an expanded set of covariates that captures the longitudinal change of Alzheimer's Disease Assessment Scale (ADAS‐cog) scores from the Alzheimer's Disease Neuroimaging Initiative study that consisted of 191 Alzheimer disease patients who were followed for 2 years. The model describes the rate of progression and baseline disease severity as a function of influential covariates. The covariates that were tested fell into 4 categories: (1) imaging volumetric measures, (2) serum biomarkers, (3) demographic and genetic factors, and (4) baseline cognitive tests. Covariates found to affect baseline disease status were years since disease onset, hippocampal volume, and ventricular volume. Disease progression rate in the model was influenced by age, total cholesterol, APOE ε4 genotype, Trail Making Test (part B) score, and current levels of impairment as measured by ADAS‐cog. Rate of progression was slower for mild and severe Alzheimer patients compared with moderate Alzheimer patients who exhibited faster rates of deterioration. In conclusion, this model describes disease progression in Alzheimer patients using novel covariates that are important for understanding the worsening of ADAS‐cog scores over time and may be useful in the future for optimizing study designs through clinical trial simulations.
Population Pharmacokinetics of Vernakalant Hydrochloride Injection (RSD1235) in Patients With Atrial Fibrillation or Atrial Flutter
Authors: Mao Zhongping Lily , Townsend Robert W. , Gao Yuying , Wheeler Jeffrey J. , Kastrissios Helen , Keirns James
Published: June 2011

Vernakalant hydrochloride is a novel, predominantly atrial‐selective antiarrhythmic drug that effectively and rapidly terminates atrial fibrillation (AF). Plasma vernakalant concentration data from 5 phase 2 and 3 clinical trials of vernakalant in patients with AF or atrial flutter and a phase 1 study in healthy volunteers were used to construct a population pharmacokinetic model. Plasma vernakalant concentration‐time data were best fit by a 2‐compartment mammillary model, with rapid first‐order elimination from the central compartment. Median systemic clearance was 0.35 L/h/kg (or 28 L/h for an 80‐kg patient), with intersubject variability estimated to be 40%. Clearance was significantly influenced by CYP2D6 genotype, age, serum creatinine concentration, and subject status (patient vs volunteer). The intercompartmental clearance was also influenced by subject status, whereas the volumes of the central compartment and peripheral compartment were unaffected by any covariates. Based on the final pharmacokinetic model, the area under the plasma vernakalant concentration‐time curve from 0 to 90 minutes was estimated to be 15% higher in CYP2D6 poor metabolizers than extensive metabolizers, with age and serum creatinine having much smaller influences on exposure. These data suggest that dose adjustments based on patient characteristics, including use of concomitant drugs, are unnecessary for intravenous vernakalant.
Stereotypes as Justifications of Prejudice
Authors: Crandall Christian S. , Bahns Angela J. , Warner Ruth , Schaller Mark
Published: June 2011

Three experiments investigate how stereotypes form as justifications for prejudice. The authors created novel content-free prejudices toward unfamiliar social groups using either subliminal (Experiment 1, N = 79) or supraliminal (Experiment 2, N = 105; Experiment 3, N = 130) affective conditioning and measured the consequent endorsement of stereotypes about the groups. Following the stereotype content model, analyses focused on the extent to which stereotypes connoted warmth or competence. Results from all three experiments revealed effects on the warmth dimension but not on the competence dimension: Groups associated with negative affect were stereotyped as comparatively cold (but not comparatively incompetent). These results provide the first evidence that—in the absence of information, interaction, or history of behavioral discrimination—stereotypes develop to justify prejudice.
Stigma, Reflected Appraisals, and Recovery Outcomes in Mental Illness
Authors: Markowitz Fred E. , Angell Beth , Greenberg Jan S.
Published: June 2011

Drawing on modified labeling theory and the reflected appraisals process and using longitudinal data from 129 mothers and their adult children with schizophrenia, we estimate models of the effects of mothers’ stigmatized identity appraisals of their mentally ill children on reflected and self-appraisals, and how appraisals affect outcomes (symptoms, self-efficacy, life satisfaction). Results indicate that initial symptoms and functioning are related to how significant others think about their ill family members, how persons with mental illness think others perceive them, and how they perceive themselves. Part of the effects of initial symptoms and functioning on reflected appraisals are due to mothers’ appraisals. A small part of the effects of outcomes on self-appraisals are due to others’ and reflected appraisals. Stigmatized self-appraisals are related to outcomes, but reflected appraisals do not affect outcomes directly. Implications for modified labeling theory and social psychological processes in recovery from mental illness are discussed.
Designing the Recipient
Authors: Hepburn Alexa , Potter Jonathan
Published: June 2011

In this paper we consider a collection of conversational practices that arise when a professional is faced with extended resistance to their offered advice. Our data is comprised of telephone calls to a UK child protection helpline. The practices we identify occur repeatedly across our corpus of advice resistance sequences and involve (1) the repackaging of resisted advice in more idiomatic form; (2) the combination of that advice with a tag question that treats the client as able to confirm the reformulated version despite their prior resistance to it; and (3) the dampening of the response requirement by continuing past the tag question, which would normally constitute a transition place for the advice recipient. We also discuss the tension between the contrasting projects of callers and call takers, which can lead to both delivery of advice and the resistance of that advice. In doing this we highlight the way in which advice may function as an element of broader institutional practices. In specifying these practices we draw upon analytic tools employed by conversation analysts, including various features of sequence organization (Schegloff 2007) and turn design (Sacks, Schegloff, and Jefferson 1974). The analysis is intended to contribute to three main areas of research: to the applied topic of managing advice resistance, to the growing literature on understanding institutional practices, and to broader concerns in conversation analytic and discursive psychological literature. These concerns include the status of the “psychological” in interaction and the specification of actions across turns and sequences of talk.
An Analysis of Pharmaceutical Experience with Decades of Rat Carcinogenicity Testing
Authors: Sistare Frank D. , Morton Daniel , Alden Carl , Christensen Joel , Keller Douglas , Jonghe Sandra De , Storer Richard D. , Reddy M. Vijayaraj , Kraynak Andrew , Trela Bruce , Bienvenu Jean-Guy , Bjurström Sivert , Bosmans Vanessa , Brewster David , Colman Karyn , Dominick Mark , Evans John , Hailey James R. , Kinter Lewis , Liu Matt , Mahrt Charles , Marien Dirk , Myer James , Perry Richard , Potenta Daniel , Roth Arthur , Sherratt Philip , Singer Thomas , Slim Rabih , Soper Keith , Fransson-Steen Ronny , Stoltz James , Turner Oliver , Turnquist Susan , van Heerden Marjolein , Woicke Jochen , DeGeorge Joseph J.
Published: June 2011

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.
The regeneration of Liverpool: Connections and disconnections in a ‘joined-up’ environment
Authors: Ellerton Thomas
Published: June 2011

Large areas of Liverpool have been undergoing regeneration in response to the city’s ongoing social and economic challenges. Within New Labour’s focus on ‘joined-up’ regeneration, this process has involved the use of a large number of single-purpose agencies, as well as other public, private and voluntary sector representatives. All of these organizations are then supposed to coordinate with each other, ensuring that there are no gaps or absences in the regeneration process. However, there are multiple issues that may affect the ability of organizations or spaces within the city to connect with each other. The research will focus on where connections and disconnections appear in the process, and explore the reasons for their occurrence. Regeneration is not a neutral activity; it is spatially and strategically selective, meaning that it may not be possible to coordinate all of the different regeneration projects, or neighbourhoods within a city. Priorities for regeneration are set at different levels, from national down to the local level, creating a structured and strategic context, meaning that some connections will be privileged over others. Regeneration is also implemented on many different scales, increasing the complexity of the process of ‘joining-up’. This article will present some initial results of research completed in Liverpool, examining the different strategies and complexities that are found within the regeneration process. The research will aim to open up issues around the complexity of coordinating different regeneration programmes and networks of urban policy. This will allow for an exploration of the debate around connections and disconnections that are created in ‘joined-up’ regeneration and also the political rationality of joining-up and its implementation in regeneration practice.
Scale-independent approach to deformation and fracture of solid-state materials
Authors: Yoshida S
Published: June 2011

As a scale-independent theory of deformation and fracture applicable to practical engineering problems, the field theoretical approach employed by physical mesomechanics is discussed in this paper. Being based on a fundamental physical principle known as gauge invariance, this approach does not rely on empirical concepts or phenomenology, and thereby is fundamentally scale independent. The derivation of physical-mesomechanical field equations is examined on a step-by-step basis, and the physical meaning of each step is clarified. Along the same line of argument, plastic deformation and transition to fracture is interpreted as an energy-dissipative process. Previously derived plastic deformation and fracture criteria are validated via detailed theoretical consideration and comparison with supporting experimental data.
Scenes from the rolling-pin war
Authors: Sengupta Kim
Published: June 2011

Afghanistan was getting almost dull when the Arab Spring began, and then Libya exploded. A foreign correspondent reports on songs, shells and a harpoon
Non-linear resonance-like processes in confined driven granular alignments and energy harvesting
Authors: Simion R P , Sen S
Published: June 2011

Energy extraction from one source and perhaps in tandem from multiple natural sources such as wind, ocean waves and perhaps geothermal resources with devices that are not susceptible to wear and tear remains an outstanding challenge. Here we propose a simple, strongly non-linear system which is potentially capable of being tuned to just about any driving frequency and amplitude. The system consists of an alignment of N elastic spheres that are barely in contact and are of fixed or variable radius and held between two ends. When a persistent driving force is imparted at an edge grain, the system can end up in an oversqueezed state. Since a mechanical system must respond to unbalanced forces, such an oversqueezed system must eventually dilate. Persistent presence of the driving force can then end up forcing the system to vacillate between the oversqueezed and dilated states. The frequencies associated with such breathing processes are non-universal, depending on the system parameters and the details of the driving force itself. This is why confined driven granular alignments can be made to respond to a wide range of frequencies and hence can turn out to be potentially useful tools for energy extraction. Here we briefly summarize our earlier work where we showed how these systems respond to a fixed driving force and then provide new results on the system response when time-dependent driving forces are involved. Needless to say, these systems may, in due course, be realized as both mechanical systems and as electrical circuits.
Using Power to Influence Outcomes
Authors: Shapiro Mary , Ingols Cynthia , Blake-Beard Stacy
Published: June 2011

The conventional definitions of power and masculinity are tightly conflated. The same words that are often used to describe power, such as authority, control, and decisiveness, are also often used to define masculinity. Where does that leave women in building and using power? Even as feminist scholars attempt to decouple the definition of power from masculinity by expanding power paradigms, cultural norms in the Unites States are still such that there is an expectation of women to be collaborative and self-sacrificing. As a result, many women are reluctant to use “masculine” power, or when they do, they are faced with the double bind: Be powerful but unfeminine. This exercise allows both female and male students to explore their personal relationship with power and how they build and use power to influence outcomes. The exercise fosters a rich discussion about cultural definitions and expectations on power and the double binds they create for both men and women.
Spontaneous Complete Regression of Gastric Large-Cell Neuroendocrine Carcinoma: Mediated by Cytomegalovirus-Induced Cross-Autoimmunity?
Authors: Ip Yiu-Tung , Pong Wai-Mei , Kao Sau-Shan , Chan John K. C.
Published: June 2011

Spontaneous regression of malignant tumour is a rare phenomenon. This report describes such an occurrence in a gastric large cell neuroendocrine carcinoma of a 77-year-old man. The patient presented with dyspepsia, and biopsy of the fungating mass in the cardia showed a high grade neuroendocrine carcinoma. The pre-operative biopsy taken after 3 months showed chronic inflammation and cytomegalovirus inclusions, but no tumour. In the gastrectomy specimen, no residual tumour was found. Instead, there were foamy histiocytes, chronic inflammatory cells and fibrovascular tissue splitting apart the muscularis propria. In addition, there was ganglionitis involving the myenteric plexus, even in areas of the stomach away from the inflamed site. Chemotherapy, radiotherapy or alternative medicine (including herbal medicine) had not been given. We postulate that cytomegalovirus infection initiated a cross-autoimmune reaction against neuronal cells, and this reaction “unintentionally” eliminated the carcinoma cells which also expressed neural antigens.
Ideological misfits
Authors: Haute Emilie van , Carty R. Kenneth
Published: June 2011

In this article, we identify a distinctive type of party member; namely, those who identify themselves as ideologically at odds with their party. Using survey evidence from nine parties in Belgium and Canada, we measure the prevalence of these ‘ideological misfits' and explore the characteristics that define them. While there appears to be no systematic cross-party pattern, it is striking that mass parties of the left have disproportionately large numbers of such members. To the extent that those parties pride themselves on intra-party democracy, this raises questions about their capacity to respond to Downsian drives towards the centre and suggests that May’s law may be one of left-wing disparity.
Reducing work-to-life interference in the public service
Authors: McCrea Rod , Boreham Paul , Ferguson Michele
Published: June 2011

Research suggests an association between participative management and lower work-to-life interference. We extend these findings to the public sector and examine possible pathways which link them, hypothesizing that participative management reduces work-to-life interference through its impact on other work attributes. Using a survey of public sector employees in Queensland, Australia and structural equation modelling, the results show that participatory management consistently reduces work-to-life interference via a number of pathways: by increasing flexibility of work hours, increasing meaningful work, reducing workload, and reducing work uncertainty. Although females with dependents work fewer hours on average, they are still more likely to have higher work-to-life interference. Overall, however, the main way participative management can reduce work-to-life interference is by reducing workloads. Participative management is normally employed to increase organizational efficiency and effectiveness; however, it can also reduce work-to-life interferences for its employees and thus assist an organization in meeting its social responsibility obligations.
The impact of weekends on outcome for acute exacerbations of COPD
Authors: Barba R. , Zapatero A. , Losa J.E. , Marco J. , Plaza S. , Rosado C. , Canora J.
Published: June 2011

Differences in hospital staffing may influence outcomes for patients with acute conditions, including acute exacerbations of chronic obstructive pulmonary disease (COPD), depending on which day of the week the patients are admitted. This study was conducted to determine whether weekend admission increases the risk of dying in hospital.

We analysed the clinical data of 289,077 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, during 2006 and 2007. We analysed the following factors for their association with death rate: day of admission, demographics, medical history and comorbidity.

During the study period, there were 35,544 (12.4%) deaths during admission in COPD patients. Weekend admissions were associated with a significantly higher in-hospital mortality (12.9%) than weekday admissions (12.1%) among COPD patients (OR 1.07 (95% CI 1.04–1.10)). The differences in mortality persisted after adjustment for age, sex and coexisting disorders (OR 1.05 (95% CI 1.02–1.08)). Analyses of deaths within 2 days after admission showed larger relative differences in mortality between the weekend and weekday admissions (OR 1.17 (95% CI 1.11–1.23)).

We conclude that patients with acute exacerbations of COPD are more likely to die in the hospital if they are admitted on a weekend compared with a weekday.
Single nucleotide polymorphism discovery in elite north american potato germplasm
Authors: Hamilton John P , Hansey Candice N , Whitty Brett R , Stoffel Kevin , Massa Alicia N , Van Deynze Allen , De Jong Walter S , Douches David S , Buell C Robin
Published: June 2011

Background

Current breeding approaches in potato rely almost entirely on phenotypic evaluations; molecular markers, with the exception of a few linked to disease resistance traits, are not widely used. Large-scale sequence datasets generated primarily through Sanger Expressed Sequence Tag projects are available from a limited number of potato cultivars and access to next generation sequencing technologies permits rapid generation of sequence data for additional cultivars. When coupled with the advent of high throughput genotyping methods, an opportunity now exists for potato breeders to incorporate considerably more genotypic data into their decision-making.

Results

To identify a large number of Single Nucleotide Polymorphisms (SNPs) in elite potato germplasm, we sequenced normalized cDNA prepared from three commercial potato cultivars: 'Atlantic', 'Premier Russet' and 'Snowden'. For each cultivar, we generated 2 Gb of sequence which was assembled into a representative transcriptome of~28-29 Mb for each cultivar. Using the Maq SNP filter that filters read depth, density, and quality, 575,340 SNPs were identified within these three cultivars. In parallel, 2,358 SNPs were identified within existing Sanger sequences for three additional cultivars, 'Bintje', 'Kennebec', and 'Shepody'. Using a stringent set of filters in conjunction with the potato reference genome, we identified 69,011 high confidence SNPs from these six cultivars for use in genotyping with the Infinium platform. Ninety-six of these SNPs were used with a BeadXpress assay to assess allelic diversity in a germplasm panel of 248 lines; 82 of the SNPs proved sufficiently informative for subsequent analyses. Within diverse North American germplasm, the chip processing market class was most distinct, clearly separated from all other market classes. The round white and russet market classes both include fresh market and processing cultivars. Nevertheless, the russet and round white market classes are more distant from each other than processing are from fresh market types within these two groups.

Conclusions

The genotype data generated in this study, albeit limited in number, has revealed distinct relationships among the market classes of potato. The SNPs identified in this study will enable high-throughput genotyping of germplasm and populations, which in turn will enable more efficient marker-assisted breeding efforts in potato.
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease
Authors: Aouizerat Bradley E , Vittinghoff Eric , Musone Stacy L , Pawlikowska Ludmila , Kwok Pui-Yan , Olgin Jeffrey E , Tseng Zian H
Published: June 2011

Background

Epidemiologic evidence suggests a heritable component to risk for sudden cardiac arrest independent of risk for myocardial infarction. Recent candidate gene association studies for community sudden cardiac arrests have focused on a limited number of biological pathways and yielded conflicting results. We sought to identify novel gene associations for sudden cardiac arrest in patients with coronary artery disease by performing a genome-wide association study.

Methods

Tagging SNPs (n = 338,328) spanning the genome were typed in a case-control study comparing 89 patients with coronary artery disease and sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation to 520 healthy controls.

Results

Fourteen SNPs including 7 SNPs among 7 genes (ACYP2, AP1G2, ESR1, DGES2, GRIA1, KCTD1, ZNF385B) were associated with sudden cardiac arrest (all p < 1.30 × 10-7), following Bonferroni correction and adjustment for population substructure, age, and sex; genetic variation in ESR1 (p = 2.62 × 10-8; Odds Ratio [OR] = 1.43, 95% confidence interval [CI]:1.277, 1.596) has previously been established as a risk factor for cardiovascular disease. In tandem, the role of 9 genes for monogenic long QT syndrome (LQT1-9) was assessed, yielding evidence of association with CACNA1C (LQT8; p = 3.09 × 10-4; OR = 1.18, 95% CI:1.079, 1.290). We also assessed 4 recently published gene associations for sudden cardiac arrest, validating NOS1AP (p = 4.50 × 10-2, OR = 1.15, 95% CI:1.003, 1.326), CSMD2 (p = 6.6 × 10-3, OR = 2.27, 95% CI:1.681, 2.859), and AGTR1 (p = 3.00 × 10-3, OR = 1.13, 95% CI:1.042, 1.215).

Conclusion

We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.
Schwann cell hamartoma: case report
Authors: Rocco Elena Guerini , Iannuzzi Francesca , Dell'Era Alessandra , Falleni Monica , Moneghini Laura , Di Nuovo Franca , Braidotti Paola , Bulfamante Gaetano , Romagnoli Solange
Published: June 2011

Background

Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening.

Case presentation

We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract.

Conclusion

As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.
Motivational Interviewing as an intervention to increase adolescent self-efficacy and promote weight loss: Methodology and design
Authors: Walpole Beverly , Dettmer Elizabeth , Morrongiello Barbara , McCrindle Brian , Hamilton Jill
Published: June 2011

Background

Childhood obesity is associated with serious physiological and psychological consequences including type 2 diabetes, higher rates of depression and low self-esteem. With the population of overweight and obese youth increasing, appropriate interventions are needed that speak to the issue of readiness to change and motivation to maintain adherence to healthy behavior changes. Motivational Interviewing (MI) is a method of therapy found to resolve ambivalence, enhance intrinsic motivation and promote confidence in a person's ability to make behavior changes. While MI has shown promise in the adult obesity literature as effecting positive lifestyle change, little is known about the effectiveness of MI with overweight and obese youth. This study aims to: 1) demonstrate that MI is an effective intervention for increasing a person's self-efficacy; 2) demonstrate that exposure to MI will facilitate healthy behavior changes; 3) explore psychological changes related to participation in MI and 4) compare physiological and anthropometric outcomes before and after intervention.

Methods/Design

The current investigation is a prospective study conducted with ongoing participants who regularly attend an outpatient pediatric care center for weight-loss. Overweight youth (BMI > 85th %ile) between the ages of 10 and 18 who meet eligibility criteria will be recruited. Participants will be randomly assigned to a control group (social skills training) or a treatment group (MI). Participants will meet with the therapist for approximately 30 minutes prior to seeing the dietician, over the course of 6 months. Participants will also undergo a full day assessment at the beginning and end of psychology intervention to evaluate body fat, and metabolic risk (screening for diabetes, high cholesterol, high blood pressure and fitness level). The paper and pencil portions of the assessments as well as the clinical testing will occur at baseline and at the conclusion of the intervention (6 months) with a repeat assessment 6 months following the completion of the intervention.

Discussion

Results from this study are expected to enhance our understanding of the efficacy of MI with children and adolescents who are overweight or obese.

Trial registration

Current Controlled Trials #NCT00326404.
A hinged external fixator for complex elbow dislocations: A multicenter prospective cohort study
Authors: Schep Niels WL , De Haan Jeroen , Iordens Gijs IT , Tuinebreijer Wim E , Bronkhorst Maarten WGA , De Vries Mark R , Goslings J Carel , Ham S John , Rhemrev Steven , Roukema Gert R , Schipper Inger B , Sintenie Jan Bernard , Van der Meulen Hub GWM , Van Thiel Tom PH , Van Vugt Arie B , Verleisdonk Egbert JMM , Vroemen Jos PAM , Wittich Philippe , Patka Peter , Van Lieshout Esther MM , Den Hartog Dennis
Published: June 2011

Background

Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures of the radial head, olecranon, or coronoid process. The majority of patients with these complex dislocations are treated with open reduction and internal fixation (ORIF), or arthroplasty in case of a non-reconstructable radial head fracture. If the elbow joint remains unstable after fracture fixation, a hinged elbow fixator can be applied. The fixator provides stability to the elbow joint, and allows for early mobilization. The latter may be important for preventing stiffness of the joint. The aim of this study is to determine the effect of early mobilization with a hinged external elbow fixator on clinical outcome in patients with complex elbow dislocations with residual instability following fracture fixation.

Methods/Design

The design of the study will be a multicenter prospective cohort study of 30 patients who have sustained a complex elbow dislocation and are treated with a hinged elbow fixator following fracture fixation because of residual instability. Early active motion exercises within the limits of pain will be started immediately after surgery under supervision of a physical therapist. Outcome will be evaluated at regular intervals over the subsequent 12 months. The primary outcome is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford Elbow Score, pain level at both sides, range of motion of the elbow joint at both sides, radiographic healing of the fractures and formation of periarticular ossifications, rate of secondary interventions and complications, and health-related quality of life (Short-Form 36).

Discussion

The outcome of this study will yield quantitative data on the functional outcome in patients with a complex elbow dislocation and who are treated with ORIF and additional stabilization with a hinged elbow fixator.

Trial Registration

The trial is registered at the Netherlands Trial Register (NTR1996).
The inpatient burden of abdominal and gynecological adhesiolysis in the US
Authors: Sikirica Vanja , Bapat Bela , Candrilli Sean D , Davis Keith L , Wilson Malcolm , Johns Alan
Published: June 2011

Background

Adhesions are fibrous bands of scar tissue, often a result of surgery, that form between internal organs and tissues, joining them together abnormally. Postoperative adhesions frequently occur following abdominal surgery, and are associated with a large economic burden. This study examines the inpatient burden of adhesiolysis in the United States (i.e., number and rate of events, cost, length of stay [LOS]).

Methods

Hospital discharge data for patients with primary and secondary adhesiolysis were analyzed using the 2005 Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Procedures were aggregated by body system.

Results

We identified 351,777 adhesiolysis-related hospitalizations: 23.2% for primary and 76.8% for secondary adhesiolysis. The average LOS was 7.8 days for primary adhesiolysis. We found that 967,332 days of care were attributed to adhesiolysis-related procedures, with inpatient expenditures totaling $2.3 billion ($1.4 billion for primary adhesiolysis; $926 million for secondary adhesiolysis). Hospitalizations for adhesiolysis increased steadily by age and were higher for women. Of secondary adhesiolysis procedures, 46.3% involved the female reproductive tract, resulting in 57,005 additional days of care and $220 million in attributable costs.

Conclusions

Adhesiolysis remain an important surgical problem in the United States. Hospitalization for this condition leads to high direct surgical costs, which should be of interest to providers and payers.
A novel subtilase with NaCl-activated and oxidant-stable activity from Virgibacillussp. SK37
Authors: Phrommao Ekkarat , Yongsawatdigul Jirawat , Rodtong Sureelak , Yamabhai Montarop
Published: June 2011

Background

Microbial proteases are one of the most commercially valuable enzymes, of which the largest market share has been taken by subtilases or alkaline proteases of the Bacillus species. Despite a large amount of information on microbial proteases, a search for novel proteases with unique properties is still of interest for both basic and applied aspects of this highly complex class of enzymes. Oxidant stable proteases (OSPs) have been shown to have a wide application in the detergent and bleaching industries and recently have become one of the most attractive enzymes in various biotechnological applications.

Results

A gene encoding a novel member of the subtilase superfamily was isolated from Virgibacillus sp. SK37, a protease-producing bacterium isolated from Thai fish sauce fermentation. The gene was cloned by an activity-based screening of a genomic DNA expression library on Luria-Bertani (LB) agar plates containing 1 mM IPTG and 3% skim milk. Of the 100,000 clones screened, all six isolated positive clones comprised one overlapping open reading frame of 45% identity to the aprX gene from Bacillus species. This gene, designated aprX-sk37 was cloned into pET21d(+) and over-expressed in E. coli BL21(DE3). The enzyme product, designated AprX-SK37, was purified by an immobilized metal ion affinity chromatography to apparent homogeneity and characterized. The AprX-SK37 enzyme showed optimal catalytic conditions at pH 9.5 and 55°C, based on the azocasein assay containing 5 mM CaCl2. Maximum catalytic activity was found at 1 M NaCl with residual activity of 30% at 3 M NaCl. Thermal stability of the enzyme was also enhanced by 1 M NaCl. The enzyme was absolutely calcium-dependent, with optimal concentration of CaCl2 at 15 mM. Inhibitory effects by phenylmethanesulfonyl fluoride and ethylenediaminetetraacetic acid indicated that this enzyme is a metal-dependent serine protease. The enzyme activity was sensitive towards reducing agents, urea, and SDS, but relatively stable up to 5% of H2O2. Phylogenetic analysis suggested that AprX-SK37 belongs to a novel family of the subtilase superfamily. We propose the name of this new family as alkaline serine protease-X (AprX).

Conclusions

The stability towards H2O2 and moderately halo- and thermo-tolerant properties of the AprX-SK37 enzyme are attractive for various biotechnological applications.
Changes of dendritic cells and fractalkine in type 2 diabetic patients with unstable angina pectoris: a preliminary report
Authors: Yao Kang , Lu Hao , Huang Rongchong , Zhang Shuning , Hong Xiaowu , Shi Hongyu , Sun Aijun , Qian Juying , Zou Yunzeng , Ge Junbo
Published: June 2011

Background

It has been shown that dendritic cells (DCs) and fractalkine play a role in accelerating progression of the inflamed atherosclerotic lesions and plaque rupture. We evaluated the numbers and functional changes of DCs and its subsets in human type 2 diabetes with or without unstable angina pectoris (UAP).

Methods

The study population consisted of 39 diabetic patients (DM:18 without CAD; DM + UAP: 21 with UAP), 18 non-diabetic UAP patients (UAP), and 15 healthy control (Normal). Peripheral blood DCs and its subsets were measured by three color flow cytometry. Serum levels of fractalkine, IL-12, and IFN-α were also measured. The functional status of the monocyte-derived DCs was analyzed by flow cytometry and allogeneic mixed T lymphocytes reaction.

Results

The percent and absolute numbers of DCs and mDC within the total leukocyte population was similar for Normal and DM, while significantly lower in DM + UAP. pDC numbers were not significantly altered. Serum fractalkine in DM + UAP was highest among the four groups (p= 0.04 vs. UAP,p= 0.0003 vs. DM,p< 0.0001 vs. Normal). Circulating mDC inversely correlated with serum fractalkine (r = -0.268,p= 0.01) level. Compared with DM and UAP, the costimulatory molecules CD86 and proliferation of T cells stimulated by DCs were significantly increased in DM + UAP group.

Conclusions

Our study suggested that increases in the fractalkine level and the number and functional changes of blood DCs might contribute to diabetic coronary atherosclerosis and plaque destabilization.
Reduced cardiac output in imported Plasmodium falciparum malaria
Authors: Herr Johanna , Mehrfar Parisa , Schmiedel Stefan , Wichmann Dominic , Brattig Norbert W , Burchard Gerd D , Cramer Jakob P
Published: June 2011

Background

Volume substitution remains subject of controversy in the light of effusions and oedema potentially complicating this highly febrile disease. Understanding the role of myocardial and circulatory function appears to be essential for clinical management. In the present study, cardiac function and cardiac proteins have been assessed and correlated with parasitological and immunologic parameters in patients with imported Plasmodium falciparum malaria.

Methods

In a prospective case-control study, 28 patients with uncomplicated and complicated P. falciparum malaria were included and findings were compared with 26 healthy controls. Cardiac function parameters were assessed by an innovative non-invasive method based on the re-breathing technique. In addition, cardiac enzymes and pro- and anti-inflammatory cytokines were measured and assessed with respect to clinical symptoms and conditions of malaria.

Results

Cardiac index (CI) as a measurement of cardiac output (CO) was 21% lower in malaria patients than in healthy controls (2.7 l/min/m2
versus 3.4 l/min/m2; P < 0.001). In contrast, systemic vascular resistance index (SVRI) was increased by 29% (32.6 mmHg⋅m2/(l/min) versus 23.2 mmHg⋅m2/(l/min); P < 0.001). This correlated with increased cardiac proteins in patients versus controls: pro-BNP 139.3 pg/ml versus 60.4 pg/ml (P = 0.03), myoglobin 43.6 μg/l versus 27.8 μg/l (P = < 0.001). All measured cytokines were significantly increased in patients with malaria. CI, SVRI as well as cytokine levels did not correlate with blood parasite density.

Conclusions

The results support previous reports suggesting impaired cardiac function contributing to clinical manifestations in P. falciparum malaria. Findings may be relevant for fluid management and should be further explored in endemic regions.
Effect of guidewire on contribution of loss due to momentum change and viscous loss to the translesional pressure drop across coronary artery stenosis: An analytical approach
Authors: Rajabi-Jaghargh Ehsan , Kolli Kranthi K , Back Lloyd H , Banerjee Rupak K
Published: June 2011

Background

Guidewire (GW) size and stenosis dimensions are the two major factors affecting the translesional pressure drop. Studying the combined effect of these parameters on the mean pressure drop (Δp) across the stenosis is of high practical importance.

Methods

In this study, time averaged mass and momentum conservation equations are solved analytically to obtain pressure drop-flow, Δp-Q, curves for three different percentage area blockages corresponding to moderate (64%), intermediate (80%), and severe (90%) stenoses. Stenosis is considered to be axisymmetric consisting of three different sections namely converging, throat, and diverging regions. Analytical expressions for pressure drop are obtained for each of these regions separately. Using this approach, effects of lesion length and GW insertion on the mean translesional pressure drop and its component (loss due to momentum change and viscous loss) are analyzed.

Results and Conclusion

It is observed that for a given percent area stenosis (AS), increase in the throat length only increases the viscous loss. However, increase in the severity of stenosis and GW insertion increase both loss due to momentum change and viscous loss. GW insertion has greater contribution to the rise in viscous loss (increase by 2.14 and 2.72 times for 64% and 90% AS, respectively) than loss due to momentum change (1.34% increase for 64% AS and 25% decrease for 90% AS). It also alters the hyperemic pressure drop in moderate (48% increase) to intermediate (30% increase) stenoses significantly. However, in severe stenoses GW insertion has a negligible effect (0.5% increase) on hyperemic translesional pressure drop. It is also observed that pressure drop in a severe stenosis is less sensitive to lesion length variation (4% and 14% increase in Δp for without and with GW, respectively) as compared to intermediate (10% and 30% increase in Δp for without and with GW, respectively) and moderate stenoses (22% and 48% increase in Δp for without and with GW, respectively). Based on the contribution of pressure drop components to the total translesional pressure drop, it is found that viscous losses are dominant in moderate stenoses, while in severe stenoses losses due to momentum changes are significant. It is also shown that this simple analytical solution can provide valuable information regarding interpretation of coronary diagnostic parameters such as fractional flow reserve (FFR).
PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro
Authors: Henken Florianne E , Banerjee N Sanjib , Snijders Peter JF , Meijer Chris JLM , De-Castro Arce Johanna , Rösl Frank , Broker Thomas R , Chow Louise T , Steenbergen Renske DM
Published: June 2011

Background

High-risk human papillomavirus (hrHPV) infections are causally related to cervical cancer development. The additional (epi)genetic alterations driving malignant transformation of hrHPV-infected cells however, are not yet fully elucidated. In this study we experimentally assessed the role of the PI3-kinase pathway and its regulator PIK3CA, which is frequently altered in cervical cancer, in HPV-induced transformation.

Methods

Cervical carcinomas and ectocervical controls were assessed for PIK3CA mRNA and protein expression by quantitative RT-PCR and immunohistochemical staining, respectively. A longitudinal in vitro model system of hrHPV-transfected keratinocytes, representing the immortal and anchorage independent phenotype, was assayed for PI3-kinase activation and function using chemical pathway inhibition i.e. LY294002 treatment, and PIK3CA RNA interference. Phenotypes examined included cellular viability, migration, anchorage independent growth and differentiation. mRNA expression of hTERT and HPV16 E6E7 were studied using quantitative RT-PCR and Northern blotting.

Results

Cervical carcinomas showed significant overexpression of PIK3CA compared to controls. During HPV-induced transformation in vitro, expression of the catalytic subunit PIK3CA as well as activation of downstream effector PKB/AKT progressively increased in parallel. Inhibition of PI3-kinase signalling in HPV16-transfected keratinocytes by chemical interference or siRNA-mediated silencing of PIK3CA resulted in a decreased phosphorylation of PKB/AKT. Moreover, blockage of PI3-kinase resulted in reduced cellular viability, migration, and anchorage independent growth. These properties were accompanied with a downregulation of HPV16E7 and hTERT mRNA expression. In organotypic raft cultures of HPV16- and HPV18-immortalized cells, phosphorylated PKB/AKT was primarily seen in differentiated cells staining positive for cytokeratin 10 (CK10). Upon PI3-kinase signalling inhibition, there was a severe impairment in epithelial tissue development as well as a dramatic reduction in p-PKB/AKT and CK10.

Conclusion

The present data indicate that activation of the PI3-kinase/PKB/AKT pathway through PIK3CA regulates various transformed phenotypes as well as growth and differentiation of HPV-immortalized cells and may therefore play a pivotal role in HPV-induced carcinogenesis.