bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended-Release Niacin Therapy and Risk of Ischemic Stroke in Patients With Cardiovascular Disease
Authors: Teo Koon K. , Goldstein Larry B. , Chaitman Bernard R. , Grant Shannon , Weintraub William S. , Anderson David C. , Sila Cathy A. , Cruz-Flores Salvador , Padley Robert J. , Kostuk William J. , Boden William E. 
Published: July 2013

Background and Purpose—
In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN.

Methods—
This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk.

Results—

There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500–2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00–3.17;
P
=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82–7.05;
P
=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23–3.88;
P
=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25–6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002–5.30 comparing the highest with the lowest tertile; overall
P
=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97–3.11;
P
=0.063).

Conclusions—
Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00120289.
Age-Related Decline in Oligodendrogenesis Retards White Matter Repair in Mice
Authors: Miyamoto Nobukazu , Pham Loc-Duyen D. , Hayakawa Kazuhide , Matsuzaki Toshinori , Seo Ji Hae , Magnain Caroline , Ayata Cenk , Kim Kyu-Won , Boas David , Lo Eng H. , Arai Ken 
Published: July 2013

Background and Purpose—
Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask whether, compared with young brains, white matter regions in older brains may be more vulnerable in part because of decreased rates of compensatory oligodendrogenesis after injury.

Methods—

A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month-old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells to sublethal 7-day CoCl
2
treatment to induce chemical hypoxic stress.

Results—
Baseline myelin density in the corpus callosum was similar in 2-month and 8-month-old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in cyclic AMP response element-binding protein signaling may be involved because activating cyclic AMP response element-binding protein with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of oligodendrocyte precursor cells.

Conclusions—
An age-related decline in cyclic AMP response element-binding protein–mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate cyclic AMP response element-binding protein signaling provide a potential therapeutic approach for treating white matter injury in aging brains.
Influences of Circulation and Climate Change on European Summer Heat Extremes
Authors: Clark Robin T. , Brown Simon J. 
Published: July 2013

Atmospheric circulation patterns occurring on the warmest 10% of summer days for a region of Europe severely impacted by the 2003 heatwave have been identified using a perturbed parameter ensemble of regional high-resolution climate model simulations for the recent past. Changes in the frequency and duration of these circulation types, driven by the simulations following a moderate transient pathway of anthropogenic emissions, are then shown for the period 2070 to 2100. Increases in the future probability of hot days are then attributed separately to changes in the frequency and temperature intensity of the circulation types. Changes in temperature intensity are found to have an effect 2 to 3 times larger than in frequency. The authors then consider how model uncertainty in changes of future temperature within circulation patterns compares to the uncertainty irrespective of circulation, in an attempt to exclude contributions to the overall uncertainty arising from changes in circulation. Within individual patterns, the range of meteorological physical processes may be narrower. However, no reduction in uncertainty was found when single patterns were considered. Contributions to the lack of narrowing from circulation-type duration, model vegetation root depth and changes in cloud cover, pressure gradient, and continental-scale warming are subsequently examined using relationships between changes in surface latent heat and temperature. Vegetation root depth is found to be the greatest contributor to the temperature uncertainty.
An association between body mass index and high-sensitivity C-reactive protein concentrations is influenced by age in community-dwelling persons
Authors: Kawamoto Ryuichi , Kusunoki Tomo , Abe Masanori , Kohara Katsuhiko , Miki Tetsuro 
Published: July 2013

Background High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Age and adiposity can potentially promote the production of C-reactive protein (CRP). However, only a few studies have investigated any interaction between age and adiposity on hsCRP concentrations. Methods We recruited 822 men (mean age, 61 ± 14 years) and 1097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether age, body mass index (BMI), and the interaction are significantly associated with hsCRP concentrations, independent of confounding factors. Results Multiple linear regression analyses for hsCRP showed that in men, age ( β = 0.169, P < 0.001) and BMI ( β = 0.114, P = 0.004) as well as smoking status, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), uric acid, and gamma-glutamyl transferase (GGT) were significantly associated with hsCRP; and in women, age ( β = 0.203, P < 0.001) and BMI ( β = 0.225, P < 0.001) as well as HDL-C, fasting plasma glucose (FPG), uric acid, GGT and high-molecular weight adiponectin were significantly associated with hsCRP. In addition to their direct associations, the interaction between age and BMI was also a significant and independent determinant for hsCRP in both men ( F = 4.407, P = 0.036) and women ( F = 5.487, P = 0.019). In participants aged < 75 years, overweight (BMI ≥25.0 kg/m2) persons were more likely to have a prevalence of elevated hsCRP concentrations (≥1.00 mg/L) compared with the normal-weight (BMI <22.0 kg/m2), but such an association was not observed in those aged ≥75 years. Conclusions Adiposity promotes low-grade systemic inflammation in community-dwelling persons aged <75 years.
Using Job-Title-Based Physical Exposures From O*NET in an Epidemiological Study of Carpal Tunnel Syndrome
Authors: Evanoff Bradley , Zeringue Angelique , Franzblau Alfred , Dale Ann Marie 
Published: July 2013

Objective: We studied associations between job-title-based measures of force and repetition and incident carpal tunnel syndrome (CTS). Background: Job exposure matrices (JEMs) are not commonly used in studies of work-related upper-extremity disorders. Method: We enrolled newly hired workers in a prospective cohort study. We assigned a Standard Occupational Classification (SOC) code to each job held and extracted physical work exposure variables from the Occupational Information Network (O*NET). CTS case definition required both characteristic symptoms and abnormal median nerve conduction. Results: Of 1,107 workers, 751 (67.8%) completed follow-up evaluations. A total of 31 respondents (4.4%) developed CTS during an average of 3.3 years of follow-up. Repetitive motion, static strength, and dynamic strength from the most recent job held were all significant predictors of CTS when included individually as physical exposures in models adjusting for age, gender, and BMI. Similar results were found using time-weighted exposure across all jobs held during the study. Repetitive motion, static strength, and dynamic strength were correlated, precluding meaningful analysis of their independent effects. Conclusion: This study found strong relationships between workplace physical exposures assessed via a JEM and CTS, after adjusting for age, gender, and BMI. Though job-title-based exposures are likely to result in significant exposure misclassification, they can be useful for large population studies where more precise exposure data are not available. Application: JEMs can be used as a measure of workplace physical exposures for some studies of musculoskeletal disorders.
Cumulative Spine Loading and Clinically Meaningful Declines in Low-Back Function
Authors: Marras William S. , Ferguson Sue A. , Lavender Steven A. , Splittstoesser Riley E. , Yang Gang 
Published: July 2013

Objective: The objective was to assess the role of cumulative spine loading measures in the development of a clinically meaningful decline in low-back function. Background: Cumulative spine loading has been a suspected risk factor for low-back pain for many years, yet the measures that characterize risk have not been well delineated. Methods: A total of 56 cumulative exposure measures were collected in a prospective field study of distribution center workers. An individual’s risk for a clinically meaningful decline in low-back function (true cases) was explored with daily, weekly, and job tenure cumulative exposure measures using univariate and multivariate statistical modeling techniques. True noncases were individuals with no decline in low-back function. Results: An individual’s risk for a clinically meaningful decline in low-back function (true cases) was predicted well versus true noncases (sensitivity/specificity = 72%/73%) using initial low-back function (p(n)), cumulative rest time, cumulative load exposure, job satisfaction, and worker age. Conclusions: Cumulative rest time was identified as an important component for predicting an individual’s risk for a clinically meaningful decline in low-back function. Application: This information can be used to assess cumulative spine loading risk and may help establish guidelines to minimize the risk of a clinically meaningful decline in low-back function.
Box Shape Influences the Size-Weight Illusion During Individual and Team Lifting
Authors: Amazeen Eric L. 
Published: July 2013

Objective: The effects of box shape—specifically width and height—on the perception of heaviness were evaluated during individual and team lifting. Background: Large objects are perceived to be as much as 50% lighter than smaller objects with the same mass. This size-weight illusion presents an obvious risk when lifting large and heavy boxes. Recent research has shown that shape influences this illusion. Specifically, increases in length and width do not produce identical decreases in perceived heaviness. However, this effect has been documented only in individual lifting, mostly with small objects. Method: Individuals and teams lifted large boxes and reported their perceptions of heaviness. The mass, height, and width of the boxes were varied independently to determine their unique effects on perceived heaviness. Results: For both types of lift, increasing width produced a greater mean illusory drop (expressed as a percentage decrease with 95% confidence intervals) in perceived heaviness (24 ± 7% during individual lifting and 41 ± 8% during team lifting) than increasing height (15 ± 7% during individual lifting and 18 ± 8% during team lifting). Conclusion: Size and shape are important factors in perceiving the heaviness of boxes during both individual and team lifting. Application: To avoid misperceiving weight and risking injury, lifters should be careful when approaching larger (especially wider) boxes.
Regulatory Forum Opinion Piece*
Authors: Konishi Yoichi , Hayashi Shim-mo , Fukushima Shoji 
Published: July 2013

The advancement of technology and the growth of international commerce underscore the need for global harmonization of regulatory safety requirements and their assessment pertaining to consumer products such as drugs, medical devices, and food. This need is particularly relevant when safety requirements involve time-intensive and costly animal safety studies. Here we present the current regulatory requirements in Europe, the United States, and Japan for flavoring substances (FSs) used in foods and point out significant differences relevant to the international standardization for safety assessments that in our opinion need to be addressed and overcome. The safety assessments that are carried out for FSs in various countries are influenced by divergent definitions of FS, by the information required and available for regulatory submission, and by different regulatory procedures, including the use of decision tree approaches. The European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) are making efforts to improve and harmonize the safety assessment of FSs. The application of in silico methods such as quantitative structure–activity relationships and read-across strategies relying on expert input are useful as a first-step screening of the assessment. Application of the Threshold of Toxicological Concern (TTC) approach permits conclusions that are compatible with the risk assessment approaches currently used by international advisory committees. The Japanese Regulatory Authority, on the other hand, does not yet consider in silico methods but still requires in vivo and in vitro genotoxicity test data as well as repeat-dose 90-day toxicity data in at least one species, to be submitted as the first step in the safety assessment of FSs. With this article, we echo requests that have been made for xenobiotics by the pharmaceutical industry worldwide, extending them to food-related products, especially FSs. We encourage regulatory agencies to adopt globally harmonized safety assessment procedures, regulatory guidelines, and review practices for FSs to foster global trade and to reduce costs and laboratory animal use.
An evaluation of treatment integrity in a randomized trial of behavioural therapy for low mood in stroke patients with aphasia
Authors: Thomas Shirley A , Russell Claire , Seed Ruth , Worthington Esme , Walker Marion F , Macniven Jamie A , Lincoln Nadina B 
Published: July 2013

Objective: To assess the treatment integrity of behavioural therapy for low mood in stroke patients with aphasia. Design: Participants were recruited to a multicentre randomized controlled trial (Communication and Low Mood; CALM trial) comparing behavioural therapy with a usual care control group. Subjects: Of the 51 participants randomly allocated to receive behavioural therapy, 44 participants completed treatment. Methods: Participants were assessed on measures of disability, language and mood. The number and length of therapy sessions, and therapist was recorded. Allocation of time to therapy components was compared across three phases of therapy. Associations between levels of disability, aphasia, mood and the therapy patients received were determined. Therapy content was compared between centres and at the beginning and end of the trial. Results: The mean number of therapy sessions was 9.1 (range 3–18, SD 2.6) and the mean duration of sessions was 58 minutes (range 30–89 minutes, SD 10.7). Allocation of time to each therapy component significantly differed across the three phases of therapy ( P < 0.05). There were no significant associations ( P > 0.05) between the length and number of sessions and patients’ aphasia, mood or disability, suggesting similar levels of therapy were provided regardless of patients’ characteristics. The content of therapy showed some differences between centres ( P < 0.01) and there was programme drift in some components of therapy. Conclusions: The results support the ability of the therapists to deliver behavioural therapy according to the treatment manual. However there were differences between centres and over time in some components of therapy.
The use of patient-specific measurement instruments in the process of goal-setting: a systematic review of available instruments and their feasibility
Authors: Stevens Anita , Beurskens Anna , Köke Albère , van der Weijden Trudy 
Published: July 2013

Objective: The aim of this study was to identify the currently available patient-specific measurement instruments used in the process of goal-setting and to assess their feasibility. Methods: After a systematic search in PubMed, EMBASE, CINAHL, PsychINFO and REHABDATA, patient-specific instruments were included, structured in a goal-setting practice framework and subjected to a qualitative thematic analysis of feasibility. Results: A total of 25 patient-specific instruments were identified and 11 were included. These instruments can be used for goal negotiation, goal-setting and evaluation. Each instrument has its own strengths and weaknesses during the different phases of the goal-setting process. Objective feasibility data were revealed for all instruments such as administration time, instruction, training and availability. Subjective feasibility could only be analysed for the Canadian Occupational Performance Measure, Goal Attainment Scaling, Self-Identified Goal Assessment and Talking Mats. Relevant themes were that Canadian Occupational Performance Measure and Goal Attainment Scaling were time consuming and difficult for patients with cognitive problems, but they facilitated goal-setting in a client-centred approach. Talking Mats was especially feasible for patients with cognitive and communication impairments. Conclusions: A total of 11 instruments were identified, and although some had strong points, there is no single good instrument that can be recommended specifically. Applying a combination of the strengths of the available instruments within a goal-setting framework can improve goal setting and tailor it to individual patients.
Accelerated Weightbearing Rehabilitation After Matrix-Induced Autologous Chondrocyte Implantation in the Tibiofemoral Joint
Authors: Edwards Peter K. , Ackland Timothy R. , Ebert Jay R. 
Published: July 2013

Background: Matrix-induced autologous chondrocyte implantation (MACI) has become an established technique for the repair of full-thickness chondral defects in the knee, although best patient outcomes appear limited by a lack of evidence-based knowledge on how to progressively increase postoperative weightbearing (WB) and rehabilitation exercises. Hypothesis: To determine the safety and efficacy of an accelerated WB regimen after MACI in the tibiofemoral joint. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Clinical and radiological assessments were performed in 28 knees at 12 months after MACI to the medial or lateral femoral condyle. Both rehabilitation interventions sought to protect the implant for an initial period and then incrementally increase load bearing. Under the “accelerated” (AR) protocol, patients reached full WB at 6 weeks after surgery compared with 8 weeks for what was considered to be the current “best practice” (CR) WB regimen based on previous research. Assessments included the Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey (SF-36), visual analog scale, 6-minute walk test, and active knee range of motion (ROM). High-resolution magnetic resonance imaging (MRI) was used to describe the quality and quantity of repair tissue via the assessment of pertinent parameters of graft repair as well as an MRI composite score. Results: Patients in both groups demonstrated significant improvement ( P < .05) in all clinical measures over the preoperative and postoperative timeline from before surgery to 12 months after surgery. The AR group reported significantly better ( P < .05) SF-36 physical component scores at 8 weeks and significantly greater ( P < .05) KOOS quality of life scores at 6 and 12 months postoperatively. Although no differences ( P > .05) were observed between the 2 groups for active knee ROM, the AR group did achieve full active knee extension as early as 4 weeks compared with the CR group at 12 weeks. There was no difference ( P > .05) in graft quality as assessed by MRI (MOCART composite score: AR, 3.34; CR, 3.04), with no patients suffering any adverse effects from the implant up to 12 months, regardless of the rehabilitation protocol employed. Conclusion: The AR approach that reduced the length of time spent ambulating on crutches resulted in improved general physical function and quality of life and an earlier attainment of full active knee extension when compared with the CR approach. There were no graft complications ascertained through MRI. This regimen appears safe and may potentially speed up the recovery of normal gait function. A larger patient cohort and follow-up are required to observe long-term graft outcomes.