bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a feasibility randomised controlled trial (RCT) for WATCH IT: a programme for obese children and adolescents
Authors: Bryant Maria , Farrin Amanda , Christie Deborah , Jebb Susan A , Cooper Ashley R , Rudolf Mary 
Published: October 2011

Background In the evaluation of childhood obesity interventions, few researchers undertake a rigorous feasibility stage in which the design and procedures of the evaluation process are examined. Consequently, phase III studies often demonstrate methodological weaknesses. Purpose Our aim was to conduct a feasibility trial of the evaluation of WATCH IT, a community obesity intervention for children and adolescents. We sought to determine an achievable recruitment rate; acceptability of randomisation, assessment procedures, and dropout rate; optimal outcome measures for the definitive trial; and a robust sample size calculation. Method Our goal was to recruit 70 participants over 6 months, randomise them to intervention or control group, and retain participation for 12 months. Assessments were taken prior to randomisation and after 6 and 12 months. Procedures mirrored those intended for a full-scale trial, but multiple measures of similar outcomes were included as a means to determine those most appropriate for future research. Acceptability of the research and impact of the research on the programme were ascertained through interviewing participants and staff. Results We recruited 70 participants and found that randomisation and data collection procedures were acceptable. Self-referral ( via media promotion) was more effective than professional referral. Blinding of assessors was sustained to a reasonable degree, and optimal outcome measures for a full-scale trial were identified. Estimated sample size was significantly greater than sample sized reported in published trials. There was some negative impact on the existing programme as a result of the research, a lesson for designers of future trials. Limitations We successfully recruited socially disadvantaged families, but the majority of families were of White British nationality. The composition of the participants was an added valuable lesson, suggesting that recruitment strategies to obtain a more heterogeneous ethnic sample warrant consideration in future research. Conclusions This study provided us with confidence that we can run a phase III multi-centre trial to test the effectiveness of WATCH IT. Importantly, it was invaluable in informing the design not only of that trial but also of future evaluations of childhood obesity treatment interventions.
Data and safety monitoring policy for National Institute of Allergy and Infectious Diseases clinical trials
Authors: Dixon Dennis O , Weiss Susanna , Cahill Kelly , Fox Lawrence , Love Joni , McNamara James , Soto-Torres Lydia E 
Published: October 2011

Background Historically, four divisions of the National Institute of Allergy and Infectious Diseases (NIAID) that manage clinical trials and oversee data and safety monitoring have operated fairly autonomously with respect to their approaches to Data and Safety Monitoring Board (DSMB) operations. We recognized the need for a revised policy on DSMB operations in an effort to encourage greater harmonization of procedures across the four divisions. Purpose The purpose of this article is to describe the considerations that motivated the development of the new policy, summarize current DSMB policies and ongoing harmonization efforts across the four divisions, and offer some recommendations for DSMB operations in the hope that other organizations may benefit from our experience. Methods From 2005 to 2009, a working group undertook a review of DSMB responsibilities, policies, and operations. We analyzed and summarized the final policy document that the working group produced, gathered data describing current DSMB activities, and developed a tabular, cross-sectional overview highlighting how divisions are harmonizing their DSMB operations. Results In 2010, there were 44 DSMBs in NIAID monitoring 169 protocols, and those DSMBs conducted 209 reviews of the protocols. Review and analysis of DSMB practices across the four divisions have led to recommendations for efficient and successful DSMB operations: adopt an inclusive approach, whereby the trial investigators assist in the process of forming and utilizing DSMBs; structures other than DSMBs can often provide many of the features of DSMBs but with greater flexibility in membership, access to interim data, and scheduling; the trial protocol should specify what safety and other concerns should trigger a DSMB review and what data should be included in prespecified reviews; present data in thoughtful and user-friendly ways that answer specific questions; allow sufficient time to plan for working with the DSMB. Limitations We recognize that NIAID’s specific circumstances and DSMB policy may not apply to the operation of DSMBs in every organization. Nevertheless, we believe that useful lessons can be learned from our experiences and efforts toward harmonization. Conclusions Homogeneity in DSMB operations and management has appeal as a matter of organizational policy and efficiency. Some limited flexibility, as long as it honors fundamental principles of independence, confidentiality of interim trial results, and clear lines of reporting and approval, may be appropriate on occasion. NIAID’s 2009 institute-level policy established a collective understanding of the important contribution that DSMBs make to the responsible conduct of clinical trials. Thinking will continue to evolve, leading to further policy refinements and the continued assurance of patient safety in our clinical trials.
AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice
Authors: Tamai Hayato , Miyake Koichi , Yamaguchi Hiroki , Takatori Miyuki , Dan Kazuo , Inokuchi Koiti , Shimada Takashi 
Published: October 2011

Abstract
Mixed-lineage leukemia (MLL)/AF4-positive acute lymphoblastic leukemia (ALL) is a common type of leukemia in infants, which is associated with a high relapse rate and poor prognosis. IL24 selectively induces apoptosis in cancer cells and exerts immunomodulatory and antiangiogenic effects. We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24–transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed by activation of the caspase 8–caspase 3 apoptotic pathway. Inhibition of HOXA9 by IL24, which was independent of TNF-α, induced MEIS1 activation followed by activation of the caspase 8–caspase 3 apoptotic pathway. Thus, gene therapy using AAV8-IL24 is a promising treatment for MLL/AF4-positive ALL.
The association between residential area characteristics and mental health outcomes among men and women in Belgium
Authors: Pattyn Elise , Van Praag Lore , Verhaeghe Mieke , Levecque Katia , Bracke Piet 
Published: October 2011

AbstractAimRecently, interest has grown in the association between contextual factors and health outcomes. This study questions whether mental health complaints vary according to the socio-economic characteristics of the residential area where people live. The gender-specific patterns are studied.MethodsComplaints of depression and generalized anxiety were measured by means of the relevant subscales of the Symptoms Checklist 90-Revised. Multilevel models were estimated with PASW statistics 18, based on a unique dataset, constructed by merging data from the Belgian Health Interview Surveys from 2001 and 2004 with data from 264 municipalities derived from Statistics Belgium and the General Socio-Economic Survey.Main findingsThe results of this exploratory study indicate that the local unemployment rate is associated with complaints of depression among women.ConclusionThis study suggests that policy should approach the male and female population differently when implementing mental health prevention campaigns.
Systemic remodeling of the redox regulatory network due to RNAi perturbations of glutaredoxin 1, thioredoxin 1, and glucose-6-phosphate dehydrogenase
Authors: Kippner Linda E , Finn Nnenna A , Shukla Shreya , Kemp Melissa L 
Published: October 2011

AbstractBackgroundCellular clearance of reactive oxygen species is dependent on a network of tightly coupled redox enzymes; this network rapidly adapts to oxidative conditions such as aging, viral entry, or inflammation. Current widespread use of shRNA as a means to perturb specific redox couples may be misinterpreted if the targeted effects are not monitored in the context of potential global remodeling of the redox enzyme network.ResultsStable cell lines containing shRNA targets for glutaredoxin 1, thioredoxin 1, or glucose-6-phosphate dehydrogenase were generated in order to examine the changes in expression associated with altering cytosolic redox couples. A qRT PCR array revealed systemic off-target effects of altered antioxidant capacity and reactive oxygen species formation. Empty lentiviral particles generated numerous enzyme expression changes in comparison to uninfected cells, indicating an alteration in antioxidant capacity irrespective of a shRNA target. Of the three redox couples perturbed, glutaredoxin 1, attenuation produced the most numerous off-target effects with 10/28 genes assayed showing statistically significant changes. A multivariate analysis extracted strong co-variance between glutaredoxin 1 and peroxiredoxin 2 which was subsequently experimentally verified. Computational modeling of the peroxide clearance dynamics associated with the remodeling of the redox network indicated that the compromised antioxidant capacity compared across the knockdown cell lines was unequally affected by the changes in expression of off-target proteins.ConclusionsOur results suggest that targeted reduction of redox enzyme expression leads to widespread changes in off-target protein expression, changes that are well-insulated between sub-cellular compartments, but compensatory in both the production of and protection against intracellular reactive oxygen species. Our observations suggest that the use of lentivirus can in itself have off-target effects on dynamic responses to oxidative stress due to the changes in species concentrations.
Quantification of the whole-body burden of radiographic osteoarthritis using factor analysis
Authors: Nelson Amanda E , DeVellis Robert F , Renner Jordan B , Schwartz Todd A , Conaghan Philip G , Kraus Virginia B , Jordan Joanne M 
Published: October 2011

Abstract

Introduction

Although osteoarthritis (OA) commonly involves multiple joints, no widely accepted method for quantifying whole-body OA burden exists. Therefore, our aim was to apply factor analytic methods to radiographic OA (rOA) grades across multiple joint sites, representing both presence and severity, to quantify the burden of rOA.

Methods

We used cross-sectional data from the Johnston County Osteoarthritis Project. The sample (n = 2092) had a mean age of 65 ± 11 years, body mass index (BMI) 31 ± 7 kg/m2, with 33% men and 34% African Americans. A single expert reader (intra-rater κ = 0.89) provided radiographic grades based on standard atlases for the hands (30 joints, including bilateral distal and proximal interphalangeal [IP], thumb IP, metacarpophalangeal [MCP] and carpometacarpal [CMC] joints), knees (patellofemoral and tibiofemoral, 4 joints), hips (2 joints), and spine (5 levels [L1/2 to L5/S1]). All grades were entered into an exploratory common factor analysis as continuous variables. Stratified factor analyses were used to look for differences by gender, race, age, and cohort subgroups.

Results

Four factors were identified as follows: IP/CMC factor (20 joints), MCP factor (8 joints), Knee factor (4 joints), Spine factor (5 levels). These factors had high internal consistency reliability (Cronbach's α range 0.80 to 0.95), were not collapsible into a single factor, and had moderate between-factor correlations (Pearson correlation coefficient r = 0.24 to 0.44). There were no major differences in factor structure when stratified by subgroup.

Conclusions

The 4 factors obtained in this analysis indicate that the variables contained within each factor share an underlying cause, but the 4 factors are distinct, suggesting that combining these joint sites into one overall measure is not appropriate. Using such factors to reflect multi-joint rOA in statistical models can reduce the number of variables needed and increase precision.
Conventional and advanced magnetic resonance imaging in tumefactive demyelination
Authors: Saini Jitender , Chatterjee Somenath , Thomas Bejoy , Kesavadas Chandrasekharan 
Published: October 2011

Background Tumefactive demyelination (TD) is a relatively uncommon entity which mimics other focal intracranial lesions. Conventional radiological findings in tumefactive demyelination have been well described. However, DTI and MRS findings in TD have not been studied in detail. Purpose To evaluate the usefulness of conventional magnetic resonance imaging (MRI), multivoxel 1H spectroscopy (MRS) and diffusion tensor imaging (DTI) in diagnosis and follow-up of TD of the brain. Material and Methods Clinical and imaging findings of 18 patients were reviewed. MR imaging data which included conventional imaging as well as MRS and DTI were reviewed. At TE 135ms MRS various metabolite ratios were calculated at different depths of the demyelinating lesions. At TE 30 ms, glutamate-glutamine (GLX-2.1–2.5 ppm) was compared in the lesion to the contralateral normal side. DTI data were available for 15 patients and Dav (mean diffusivity) and trace values were recorded from central and peripheral layers of the index lesion. Histopathological (9 patients) and therapeutic response (9 patients) on follow-up imaging were taken as the diagnostic criterion. In addition, the follow-up MRI scans available were also reviewed. Results Characteristic peripheral ‘broken ring’ type of contrast enhancement was noted in 12 cases. Two or three concentric distinct zones were noted on imaging with distinct metabolic and structural signature in most cases. On TE 135ms, the central part showed variable Choline (Cho) and significantly low N-Acetyl Aspartate (NAA). DTI demonstrated high Dav and very low trace value in this zone. The intermediate area showed higher Cho and lower NAA compared to contralateral normal side. The outermost layer, which corresponded to the contrast enhancing areas on MRI, showed high Cho, lower NAA, and restricted diffusion on DTI. The GLX increase was noted in tumefactive lesions. Lactate was observed in all patients and it appeared higher at the center compared to the periphery of lesions. Follow-up imaging showed shrinkage of index lesions, disappearance of contrast enhancement, and diffusion restriction. MRS showed, persistent abnormalities on follow-up imaging. Conclusion Tumefactive demyelinating lesions reveal different microstructural changes at different depths of the lesion and this unique feature may be useful in differentiating them from other focal lesions of brain.
Alternative methods to a TaqMan assay to detect a tri-allelic single nucleotide polymorphism rs757210 in the HNF1β gene
Authors: Swen Jesse J. , Baak-Pablo Renee F. , Guchelaar Henk-Jan , van der Straaten Tahar 
Published: October 2011

AbstractSeveral studies report difficulties in genotypingPyrosequencing and high resolution melting analysis of small amplicons (HRM) were developed and tested in panels of type 2 diabetes mellitus patients (n=258) and healthy blood donors (n=183). Results were confirmed by Sanger sequencing.With pyrosequencing, allele frequencies for the A, G and C allele of 0.42, 0.56, 0.02 and 0.37, 0.62, 0.01 were established in the panel of type 2 diabetes mellitus patients and healthy blood donors, respectively. Similar results were found using the more routinely available HRM method. Results for pyrosequencing and HRM were in 99.6% concordance.Pyrosequencing and HRM can be used to genotype the tri-allelic SNP rs757210 in the
Overlooked and Underserved: “Action Signs” for Identifying Children With Unmet Mental Health Needs
Authors: Jensen Peter S. , Goldman Eliot , Offord David , Costello Elizabeth J. , Friedman Robert , Huff Barbara , Crowe Maura , Amsel Lawrence , Bennett Kathryn , Bird Hector , Conger Rand , Fisher Prudence , Hoagwood Kimberly , Kessler Ronald C. , Roberts Robert 
Published: October 2011

OBJECTIVE:
The US Surgeon General has called for new approaches to close the mental health services gap for the large proportion of US children with significant mental health needs who have not received evaluation or services within the previous 6 to 12 months. In response, investigators sought to develop brief, easily understood, scientifically derived “warning signs” to help parents, teachers, and the lay public to more easily recognize children with unmet mental health needs and bring these children to health care providers' attention for evaluation and possible services.

METHOD:
Analyses of epidemiologic data sets from &gt;6000 children and parents were conducted to (1) determine the frequency of common but severely impairing symptom profiles, (2) examine symptom profile frequencies according to age and gender, (3) evaluate positive predictive values of symptom profiles relative to Diagnostic and Statistical Manual of Mental Disorders diagnoses, and (4) examine whether children with 1 or more symptom profiles receive mental health services.

RESULTS:
Symptom-profile frequencies ranged from 0.5% to 2.0%, and 8% of the children had 1 or more symptom profile. Profiles generated moderate-to-high positive predictive values (52.7%–75.4%) for impairing psychiatric diagnoses, but fewer than 25% of children with 1 or more profiles had received services in the previous 6 months.

CONCLUSIONS:
Scientifically robust symptom profiles that reflect severe but largely untreated mental health problems were identified. Used as “action signs,” these profiles might help increase public awareness about children's mental health needs, facilitate communication and referral for specific children in need of evaluation, and narrow the child mental health services gap.
Parent Education by Maternity Nurses and Prevention of Abusive Head Trauma
Authors: Altman Robin L. , Canter Jennifer , Patrick Patricia A. , Daley Nancy , Butt Neelofar K. , Brand Donald A. 
Published: October 2011

OBJECTIVE:A consortium of the 19 community hospitals and 1 tertiary care children's hospital that provide maternity care in the New York State Hudson Valley region implemented a program to teach parents about the dangers of shaking infants and how to cope safely with an infant's crying. This study evaluated the effectiveness of the program in reducing the frequency of shaking injuries.METHODS:The educational program, which was delivered by maternity nurses, included a leaflet explaining abusive head trauma (“shaken baby syndrome”) and how to prevent it, an 8-minute video on the subject, and a statement signed by parents acknowledging receipt of the information and agreeing to share it with others who will care for the infant. Poisson regression analysis was used to compare the frequency of shaking injuries during the 3 years after program implementation with the frequency during a 5-year historical control period.RESULTS:Sixteen infants who were born in the region during the 8-year study period were treated at the children's hospital for shaking injuries sustained during their first year of life. Of those infants, 14 were born during the 5-year control period and 2 during the 3-year postimplementation period. The decrease from 2.8 injuries per year (14 cases in 5 years) to 0.7 injuries per year (2 cases in 3 years) represents a 75.0% reduction (P = .03).CONCLUSIONS:Parent education delivered in the hospital by maternity nurses reduces newborns' risks of sustaining an abusive head injury resulting from shaking during the first year of life.
Reducing PICU Central Line–Associated Bloodstream Infections: 3-Year Results
Authors: Miller Marlene R. , Niedner Matthew F. , Huskins W. Charles , Colantuoni Elizabeth , Yenokyan Gayane , Moss Michele , Rice Tom B. , Ridling Debra , Campbell Deborah , Brilli Richard J. ,   the National Association of Children's Hospitals and Related Institutions Pediatric Intensive Care Unit Central Line–Associated Bloodstream Infection Quality Transformation Teams
Published: October 2011

OBJECTIVES:
To evaluate the long-term impact of pediatric central line care practices in reducing PICU central line–associated bloodstream infection (CLA-BSI) rates and to evaluate the added impact of chlorhexidine scrub and chlorhexidine-impregnated sponges.

METHODS:
A 3-year, multi-institutional, interrupted time-series design (October 2006 to September 2009), with historical control data, was used. A nested, 18-month, nonrandomized, factorial design was used to evaluate 2 additional interventions. Twenty-nine PICUs were included. Two central line care bundles (insertion and maintenance bundles) and 2 additional interventions (chlorhexidine scrub and chlorhexidine-impregnated sponges) were used. CLA-BSI rates (January 2004 to September 2009), insertion and maintenance bundle compliance rates (October 2006 to September 2009), and chlorhexidine scrub and chlorhexidine-impregnated sponge compliance rates (January 2008 to June 2009) were assessed.

RESULTS:
The average aggregate baseline PICU CLA-BSI rate decreased 56% over 36 months from 5.2 CLA-BSIs per 1000 line-days (95% confidence interval [CI]: 4.4–6.2 CLA-BSIs per 1000 line-days) to 2.3 CLA-BSIs per 1000 line-days (95% CI: 1.9–2.9 CLA-BSIs per 1000 line-days) (rate ratio: 0.44 [95% CI: 0.37–0.53]; P &lt; .0001). No statistically significant differences in CLA-BSI rate decreases between PICUs using or not using either of the 2 additional interventions were found.

CONCLUSIONS:
Focused attention on consistent adherence to the use of pediatrics-specific central line insertion and maintenance bundles produced sustained, continually decreasing PICU CLA-BSI rates. Additional use of either chlorhexidine for central line entry scrub or chlorhexidine-impregnated sponges did not produce any statistically significant additional reduction in PICU CLA-BSI rates.