bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognosis and Outcome of Small (≤1 cm), Node-Negative Breast Cancer on the Basis of Hormonal and HER-2 Status
Authors: Amar Surabhi , McCullough Ann E. , Tan Winston , Geiger Xochiquetzal J. , Boughey Judy C. , McNeil Rebecca B. , Coppola Kyle E. , McLaughlin Sarah A. , Palmieri Frances M. , Perez Edith A.
Published: October 2010

Long-term outcomes and hence the role of adjuvant therapy in patients with small (≤1 cm), node-negative breast cancer remain unclear. This study's objective was to evaluate whether human epidermal growth factor receptor (HER)-2 status is an independent, poor prognostic marker in patients with these tumors and to identify a subgroup of patients with these small tumors who might benefit from adjuvant systemic therapy. All patients with a diagnosis of a node-negative breast tumor measuring ≤1 cm and available HER-2 test results between January 1, 2001, and December 31, 2005, at the three Mayo Clinic sites were identified. Clinicopathologic data were compared in three groups: HER-2−, HER-2+, and triple-negative (TN) tumors. Of the 421 tumors identified, 364 (86.5%) were HER-2−, 28 (6.7%) were HER-2+, and 29 (6.9%) were TN. The median follow-up time was 1,015 days (range, 1–2,549 days). Groups were balanced in terms of patient age and tumor histology. Eleven patients with HER-2− tumors (3.0%), seven with HER-2+ tumors (25.0%), and eight with TN tumors (27.6%) received adjuvant chemotherapy. Follow-up data were available for 357, 28, and 28 patients in the three groups, respectively. Death rates in the three groups were 6.4% (23 of 357) (one recurrence-related death), 0% (0 of 28), and 7.1% (2 of 28) (one recurrence-related death), respectively. During follow-up, the tumor recurred in nine patients: four were HER-2− tumors (1.1%), two were HER-2+ tumors (7.1%), and three were TN tumors (10.7%). Patients with small, node-negative breast tumors have an excellent prognosis, but HER-2+ and TN tumors appear to have a higher recurrence rate, warranting consideration for broad use and optimization of systemic adjuvant treatments.
Age and Axillary Lymph Node Ratio in Postmenopausal Women with T1-T2 Node Positive Breast Cancer
Authors: Vinh-Hung Vincent , Joseph Sue A. , Coutty Nadege , Ly Bevan Hong , Vlastos Georges , Nguyen Nam Phong
Published: October 2010

Learning Objectives

After completing this course, the reader will be able to: Identify changes in medical/surgical practice that can affect the prognostic performance of established prognostic factors such as lymph node involvement in breast cancer.Explain how the lymph node ratio can help to adjust against practice-related changes.Use the lymph node ratio as a measure of tumor burden in order to weigh the risk of breast cancer death against other causes of death in elderly patients.

This article is available for continuing medical education credit at CME.TheOncologist.com

Purpose.

The purpose of this article was to examine the relationship between age and lymph node ratio (LNR, number of positive nodes divided by number of examined nodes), and to determine their effects on breast cancer (BC) and overall mortality.

Methods.

Women aged ≥50 years, diagnosed in 1988–1997 with a unilateral histologically confirmed T1-T2 node positive surgically treated primary nonmetastatic BC, were selected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER). Generalized Additive Models for Location Scale and Shape (GAMLSS) were used to evaluate the age-LNR relationship. Cumulative incidence functions and multivariate competing risks analysis based on model selection by the Bayesian Information Criterion (BIC) were used to examine the effect of age and LNR on mortality. Low LNR was defined as ≤0.20, mid-LNR 0.21–0.65, and high LNR >0.65.

Results.

GAMLSS showed a nonlinear LNR-age relationship, increasing from mean LNR 0.26–0.28 at age 50–70 years to 0.30 at 80 years and 0.40 at 90 years. Compared with a 9.8% [95% confidence interval (CI) 8.8%–10.8%] risk of BC death at 5 years in women aged 50–59 years with low LNR, the risk in women ≥80 years with low LNR was 12.6% [95% CI 10.1%–15.0%], mid-LNR 18.1% [13.9%–22.1%], high LNR 29.8% [22.7%–36.1%]. Five-years overall risk of death increased from 40.8% [37.5%–43.9%] by low LNR to 67.4% [61.4%–72.4%] by high LNR. The overall mortality hazard ratio for age ≥80 years with high LNR was 7.49 [6.54–8.59], as compared with women aged 50–59 years with low LNR.

Conclusion.

High LNR combined with older age was associated with a threefold increased risk of BC death and a sevenfold increased hazard ratio of overall mortality.
Is Increasing Physical Activity Necessary to Diminish Fatigue During Cancer Treatment? Comparing Cognitive Behavior Therapy and a Brief Nursing Intervention with Usual Care in a Multicenter Randomized Controlled Trial
Authors: Goedendorp Martine M. , Peters Marlies E.W.J. , Gielissen Marieke F.M. , Witjes J. Alfred , Leer Jan Willem , Verhagen Constans A.H.H.V.M. , Bleijenberg Gijs
Published: October 2010

Background.

Two interventions for fatigue were given during curative cancer treatment. The aim of this multicenter randomized controlled trial (RCT) with three conditions was to demonstrate the efficacy and to determine the contribution of physical activity.

Methods.

Recruited from seven hospitals, 220 patients with various malignancies participated in a RCT. The brief nursing intervention (BNI) consisted of two 1-hour sessions, 3 months apart, given by 12 trained nurses, focusing only on physical activity. Cognitive behavior therapy (CBT) consisted of up to ten 1-hour sessions, within 6 months, provided by two therapists, focusing on physical activity and psychosocial elements. The control group received only usual care (UC). Assessments took place before and at least 2 months after cancer treatment, when patients had recovered from acute fatigue. Fatigue was the primary outcome. Efficacy was tested using analyses of covariance. A nonparametric bootstrap approach was used to test whether the effect on fatigue was mediated by physical activity.

Results.

The CBT group was significantly less fatigued than the UC group. Between the BNI and the UC groups, no significant difference was found in fatigue. The mediation hypothesis was rejected.

Discussion.

CBT given during curative cancer treatment proved to be an effective intervention to reduce fatigue at least 2 months after cancer treatment. The BNI was not effective. Contrary to what was expected, physical activity did not mediate the effect of CBT on fatigue. Thus, the reduction in fatigue elicited by CBT was realized without a lasting increase in physical activity.
Obesity and the Risk for a Hematological Malignancy: Leukemia, Lymphoma, or Myeloma
Authors: Lichtman Marshall A.
Published: October 2010

The aggregate of epidemiological studies indicates a significantly elevated risk for cancer in people with a high body mass index (BMI); a “dose–response” effect exists with increasing risk as BMI increases from the normal to overweight to obese categories. Successful sustained weight loss decreases future risk. The relationship of being overweight to the risk for leukemia in the aggregate has been supported in several large cohort studies and two meta-analyses of cohort and case–control studies. One meta-analysis found an elevated risk for each of the four major subtypes of leukemia. A significant association between the risk for non-Hodgkin's lymphoma and elevated BMI was supported by a meta-analysis of 13 cohort and nine case–control studies. The risk for diffuse large B-cell lymphoma may be especially significant. A high BMI increases the risk for myeloma, as judged by a meta-analysis of 11 cohort and four case–control studies. The biological relationship of obesity to the risk for cancer (biological plausibility) is unresolved. The two major causal final pathways could be “inductive” or “selective.” The metabolic, endocrinologic, immunologic, and inflammatory-like changes resulting from obesity may increase the cell mutation rate, dysregulate gene function, disturb DNA repair, or induce epigenetic changes, favoring the induction of neoplastic transformation (inductive). Alternatively, obesity may create an environment in which pre-existing clones that are dormant are permitted (selected) to emerge.
The Role of Cognitive-Behavioral Therapy in Behavioral Medicine: Introduction to the Special Issue
Authors: Hart Trevor A.
Published: October 2010

Behavioral medicine focuses on assessment, treatment, and prevention of medical problems and promotion of health, using the behavioral sciences (e.g., International Society of Behavioral Medicine). Behavioral medicine is strongly rooted in cognitive-behavioral therapy (CBT) both historically and in its use of CBT theories and techniques. The articles from the present special issue present the relation between cognition and behavior in both basic research and intervention studies. These articles extend the role of CBT into medical and public health settings, thereby expanding the ability of CBT therapists to help patients with medical problems and those who are at high risk for developing medical problems.
Acceptability of a Cognitive Behavior Therapy Intervention to Implantable Cardioverter Defibrillator Recipients
Authors: Irvine Jane , Stanley Jill , Ong Lephuong , Cribbie Robert , Ritvo Paul , Katz Joel , Dorian Paul , O’Donnell Suzan , Harris Louise , Cameron Doug , Hill Ann , Newman David , Johnson Sabine N. , Bilanovic Ana , Sears Samuel F.
Published: October 2010

We aimed to assess cardiac patients, acceptance of cognitive behavior therapy (CBT); determine if gender was associated with treatment engagement (session attendance and utilization of intervention strategies); and relate engagement to outcome. Of 193 patients receiving an implantable cardioverter defibrillator (ICD) who agreed to participate in a randomized controlled trial, 96 were randomized to CBT. Measures of treatment acceptance indicated that most participants rated counseling as “very to extremely helpful.” Gender was associated with only one treatment engagement index. Symptoms of depression and post-traumatic stress improved from baseline to 6- and 12-month follow-up. Number of counseling session attendance was not associated with outcome. Reported utilization of two of the six CBT strategies (modifying faulty thinking, correcting cognitive distortions) was associated with a better treatment outcome. In conclusion, a CBT intervention was well received by ICD patients. There was some indication that treatment engagement related to better treatment outcomes.
The Development of a Computer-Administered Cognitive-Behavioral Intervention to Promote Stress Management Among HIV+ Women
Authors: Brown Jennifer L. , Vanable Peter A. , Carey Michael P. , Elin Larry
Published: October 2010

Few interventions address the unique psychosocial needs of HIV+ women. To address this unmet need, we developed and pilot tested a brief, cognitive-behavioral computerized stress management intervention with 60 HIV+ women. This interactive intervention included modules that promoted cognitive appraisal skills, encouraged appropriate coping responses and problem solving skills, and provided relaxation training. In this report we provide an overview of the intervention and present acceptability and feasibility data from a pilot intervention trial. All participants successfully navigated the computerized program and most found the intervention to be acceptable. Overall, the results indicated that a brief, computerized stress management intervention was a feasible and acceptable approach to enhance stress management skills; use of this intervention has the potential to reduce distress and improve health outcomes among HIV+ women.
The Impact of Cognitive Interventions in Treating Depressed Breast Cancer Patients
Authors: Hopko Derek R. , Colman Lindsey K.
Published: October 2010

In behavioral medicine, there is adequate support for behavior modification strategies in reducing depression and anxiety in medical patients. There is comparably less support for cognitive interventions with these patients. Treatment outcome studies with cancer patients generally support the efficacy of cognitive–behavioral interventions, but studies have significant methodological limitations. Additionally, cognitive–behavioral therapy for depression incorporates numerous treatment components, and when examining data with nomothetic statistics, important individual differences may go unrecognized. With reference to the sudden gain literature on significant session-by-session treatment gains, this paper highlights the cognitive–behavioral treatment of two breast cancer patients with clinical depression. In addition to positive treatment outcome in which depression was significantly reduced and quality of life and medical outcomes improved, session-based sudden change data suggest that for these cancer patients, cognitive interventions were most significant in accounting for treatment gains. Findings are reviewed in the context of mechanism of change issues in the cognitive–behavioral treatment of depression.
The Future of Cognitive Behavioral Interventions Within Behavioral Medicine
Authors: Hart Stacey L. , Hart Trevor A.
Published: October 2010

There is a growing body of evidence supporting the use of cognitive behavioral treatment within behavioral medicine. There are several limitations to the current body of literature, including external validity of findings from randomized controlled trials, dissemination of findings, and the use of CBT when patients are unmotivated to make behavior change. The current paper proposes several future directions to address these limitations. Solutions to be explored in future research include practical behavioral trials, stepped care approaches, remote technology approaches such as telephone and Internet-based treatments, and the integration of motivational interviewing into cognitive behavioral treatment.
Psychotherapy According to the Socratic Method: Integrating Ancient Philosophy With Contemporary Cognitive Therapy
Authors: Overholser James C.
Published: October 2010

The Socratic method provides a useful framework for psychotherapy by integrating ideas from ancient philosophy with strategies from contemporary cognitive therapy. According to the Socratic method, four main components underlie the process of therapy: systematic questioning, inductive reasoning, universal definitions, and a sincere disavowal of knowledge in the therapist and the client. These components work together to guide the dialogue that occurs in most therapy sessions. In addition, the Socratic method often focuses on two major topical areas: self-improvement and cultivating virtue in everyday life. Through the use of the Socratic method, clients can explore important issues, clarify major life goals, and strive to improve their moral character.
Clarithromycin Accumulation by Phagocytes and Its Effect on Killing of Aggregatibacter actinomycetemcomitans
Authors: Iskandar Irma , Walters John D.
Published: October 2010

Background: Clarithromycin inhibits several periodontal pathogens and is concentrated inside gingival fibroblasts and epithelial cells by an active transporter. We hypothesized that polymorphonuclear leukocytes (PMNs) and less mature myeloid cells possess a similar transporter for clarithromycin. It is feasible that clarithromycin accumulation inside PMNs could enhance their ability to kill Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans).

Methods: To test the first hypothesis, purified PMNs and cultured HL‐60 cells were incubated with [3H]‐clarithromycin. Clarithromycin transport was assayed by measuring changes in cell‐associated radioactivity over time. The second hypothesis was examined with PMNs loaded by incubation with clarithromycin (5 μg/ml). Opsonized bacteria were incubated at 37°C with control and clarithromycin‐loaded PMNs.

Results: Mature human PMNs, HL‐60 cells differentiated into granulocytes, and undifferentiated HL‐60 cells all took up clarithromycin in a saturable manner. The kinetics of uptake by all yielded linear Lineweaver‐Burk plots. HL‐60 granulocytes transported clarithromycin with a Km of ≈250 μg/ml and a Vmax of 473 ng/min/106 cells, which were not significantly different from the values obtained with PMNs. At steady state, clarithromycin levels inside HL‐60 granulocytes and PMNs were 28‐ to 71‐fold higher than extracellular levels. Clarithromycin‐loaded PMNs killed significantly more A. actinomycetemcomitans and achieved shorter half‐times for killing than control PMNs when assayed at a bacteria‐to‐PMN ratio of 100:1 (P <0.04). At a ratio of 30:1, these differences were not consistently significant.

Conclusions: PMNs and less mature myeloid cells possess a transporter that takes up and concentrates clarithromycin. This system could help PMNs cope with an overwhelming infection by A. actinomycetemcomitans.
Periodontitis Prevalence and Severity in Indonesians With Type 2 Diabetes
Authors: Susanto Hendri , Nesse Willem , Dijkstra Pieter U. , Agustina Dewi , Vissink Arjan , Abbas Frank
Published: October 2010

Background: The prevalence of diabetes mellitus type 2 (DM2) in Indonesia is high and still rising. Periodontitis is associated with DM2. No study has investigated this association in Indonesia, nor has any study investigated this association using a variety of methods to operationalize periodontitis. The present study compares prevalence and severity of periodontitis in patients with DM2 to healthy controls, using different methods to operationalize periodontitis.

Methods: A total of 78 subjects with DM2 and 65 healthy control subjects underwent a full‐mouth periodontal screening assessing probing depth, gingival recession, plaque index, and bleeding on probing. Using these measurements, the prevalence and severity of periodontitis was operationalized in various ways. Differences in the prevalence and severity of periodontitis between subjects with DM2 and healthy subjects were analyzed using univariate analyses. In regression analyses, the prevalence and severity of periodontitis were predicted on the basis of DM2 presence, controlling for confounders and effect modification.

Results: Prevalence of periodontitis was significantly higher in subjects with DM2 compared to healthy subjects, showing odds ratios of 5.0 and 6.1. Likewise, periodontitis severity was significantly higher in subjects with DM2.

Conclusion: Indonesian subjects with DM2 had more prevalent and more severe periodontitis than healthy Indonesian subjects, independent of confounding factors or the methods used to operationalize periodontitis.
Implant Stability and Peri‐Implant Parameters in Free Vascularized Iliac Graft Transplantation Patients: Report of Three Ameloblastoma Cases
Authors: Tözüm Tolga F. , Sönmez Erhan , Askin Sezen B. , Tulunoglu Ibrahim , Safak Tunc
Published: October 2010

Background: Ameloblastoma, a benign but locally aggressive tumor, accounts for 9% to 11% of all odontogenic tumors. Radical procedures, including resection, are performed. To restore functions after resection, free vascularized iliac grafts followed by a dental implant–supported prosthesis are used as a successful treatment option. The aim of this case report is to evaluate the peri‐implant clinical status and stability of dental implants placed in patients with advanced‐stage mandibular ameloblastomas.

Methods: Examinations of three patients revealed extensive ameloblastomas, and hemimandibulectomies were performed. Six months after surgeries, two to four dental implants were placed. After 6 months of healing, one fixed prosthesis and two removable prostheses were delivered. The stability of implants was evaluated at the surgical baseline and 1, 3, 6, 9, and 12 months after surgery by resonance‐frequency (RF) analysis. Peri‐implant clinical parameters (i.e., plaque index [PI], gingival index [GI], gingival bleeding time index [GBTI], and peri‐implant probing depth [PD]) were recorded at the delivery of the prosthesis and at follow‐ups at 1, 3, and 6 months.

Results: Nine implants that supported one removable prosthesis and two fixed prostheses were placed. RF analysis revealed no significant changes in implant stability during 12 months of follow‐up. Peri‐implant clinical parameters (PI, GI, and GBTI) showed slight improvements during follow‐up. Although advancements were observed in 6 months, PDs were found to be deeper than optimal measurements for the whole observation time.

Conclusion: The implant‐supported prosthetic rehabilitation of patients with ameloblastomas reconstructed with free vascularized iliac crest grafts can be a predictive alternative for improving the quality of life of patients in which a high implant stability and acceptable peri‐implant health may be achieved.
Recruiting and Retaining Primary Care Physicians in Urban Underserved Communities: The Importance of Having a Mission to Serve
Authors: Odom Walker Kara , Ryan Gery , Ramey Robin , Nunez Felix L. , Beltran Robert , Splawn Robert G. , Brown Arleen F.
Published: October 2010

Objectives. We examined factors influencing physician practice decisions that may increase primary care supply in underserved areas.

Methods. We conducted in-depth interviews with 42 primary care physicians from Los Angeles County, California, stratified by race/ethnicity (African American, Latino, and non-Latino White) and practice location (underserved vs nonunderserved area). We reviewed transcriptions and coded them into themes by using standard qualitative methods.

Results. Three major themes emerged in relation to selecting geographic- and population-based practice decisions: (1) personal motivators, (2) career motivators, and (3) clinic support. We found that subthemes describing personal motivators (e.g., personal mission and self-identity) for choosing a practice were more common in responses among physicians who worked in underserved areas than among those who did not. By contrast, physicians in nonunderserved areas were more likely to cite work hours and lifestyle as reasons for selecting their current practice location or for leaving an underserved area.

Conclusions. Medical schools and shortage-area clinical practices may enhance strategies for recruiting primary care physicians to underserved areas by identifying key personal motivators and may promote long-term retention through work–life balance.
Approaches to Measuring the Extent and Impact of Environmental Change in Three California Community-Level Obesity Prevention Initiatives
Authors: Cheadle Allen , Samuels Sarah E. , Rauzon Suzanne , Yoshida Sallie C. , Schwartz Pamela M. , Boyle Maria , Beery William L. , Craypo Lisa , Solomon Loel
Published: October 2010

Despite growing support among public health researchers and practitioners for environmental approaches to obesity prevention, there is a lack of empirical evidence from intervention studies showing a favorable impact of either increased healthy food availability on healthy eating or changes in the built environment on physical activity. It is therefore critical that we carefully evaluate initiatives targeting the community environment to expand the evidence base for environmental interventions.

We describe the approaches used to measure the extent and impact of environmental change in 3 community-level obesity-prevention initiatives in California. We focus on measuring changes in the community environment and assessing the impact of those changes on residents most directly exposed to the interventions.
Asymmetry and Collusion in Sequential Procurement: A "Large Lot Last" Policy
Authors: Albano Gian Luigi , Spagnolo Giancarlo
Published: October 2010

Sequential procurement of multiple contracts/lots is widespread and often regularly repeated. We analyze how sequentiality and its interaction with asymmetries across bidders and lots affect the sustainability of supplier/bidder collusion. Sequential procurement stabilizes supplier collusion (compared to simultaneous procurement) by allowing not only to identify or punish deviations within the sequence, but also to allocate the last lot to the bidder with the highest incentive to defect. We then analyze how to counteract these effects by exploiting (or creating) asymmetries in the value of lots, finding that the most effective policy procures the most valuable lot at the end of each sequence.
Large Artery Calcification on Dialysis Patients Is Located in the Intima and Related to Atherosclerosis
Authors: Coll Blai , Betriu Angels , Martínez-Alonso Montserrat , Amoedo Maria Luisa , Arcidiacono Maria Vittoria , Borras Merce , Valdivielso Jose Manuel , Fernández Elvira
Published: October 2010

Background and objectives

Vascular calcification (VC) has a significant effect in cardiovascular diseases on dialysis patients. However, VC is assessed with x-ray-based techniques, which do not inform about calcium localization (intima, media, atherosclerosis-related). The aim of this work is to study VC and its related factors using arterial ultrasound to report the exact location of calcium.

Design, setting, participants, & measurements

This was an observational, cross-sectional, case-control study that included 232 patients in dialysis and 208 age- and sex-matched controls with normal kidney function. Demographic data and laboratory values were collated. Carotid, femoral, and brachial ultrasounds were performed to assess VC and atherosclerosis burden using a standardized protocol.

Results

Cardiovascular risk factors were predominantly found in controls, although the burden of atherosclerosis was higher in the dialysis group. VC was significantly more prevalent in the group of patients on dialysis than control subjects, and in both groups the most prevalent pattern of VC was linear calcification located in the intima of the artery wall. Age and undergoing dialysis (with or without previous cardiovascular diseases) were positively and significantly associated with linear calcification. Conversely, the absence of atherosclerosis and low levels of C-reactive protein and phosphorus significantly impeded the development of linear calcification.

Conclusions

VC in large, conduit arteries is more prevalent in patients on dialysis than controls and is predominantly located in a linear fashion in the intima of the arteries.
Fetuin-A Levels Are Increased in Patients With Type 2 Diabetes and Peripheral Arterial Disease
Authors: Lorant David Peter , Grujicic Milan , Hoebaus Clemens , Brix Johanna-Maria , Hoellerl Florian , Schernthaner Guntram , Koppensteiner Renate , Schernthaner Gerit-Holger
Published: October 2010

OBJECTIVE

Low levels of fetuin-A, a systemic calcification inhibitor, are linked to mortality in patients on dialysis. In contrast, elevated fetuin-A is associated with cardiovascular events in non-renal patients. We investigated fetuin-A in patients with type 2 diabetes and peripheral arterial disease (PAD).

RESEARCH DESIGN AND METHODS

We studied fetuin-A in 76 patients with PAD and normal glucose metabolism (NGM-PAD) and in 129 patients with PAD and type 2 diabetes (type 2 diabetes–PAD). Additionally, 40 patients with diabetes without any complications (type 2 diabetes–non-PAD) were examined.

RESULTS

Type 2 diabetes–PAD subjects (399 ± 155 μg/ml) had significantly higher fetuin-A levels than type 2 diabetes–non-PAD subjects (247 ± 42; P < 0.001). In NGM-PAD subjects (376 ± 144), fetuin-A was significantly higher than in type 2 diabetes–non-PAD subjects (P < 0.001). Type 2 diabetes–PAD patients with mediasclerosis had lower fetuin-A than subjects without (P < 0.03). Regression analysis in type 2 diabetes–PAD subjects revealed that glycated A1C (P < 0.001) and mediasclerosis (P = 0.004) were the strongest predictors of fetuin-A. Multivariate regression revealed that a 1-SD increase in fetuin-A was associated with an odds ratio (OR) of 2.1 (95% CI 1.1–3.3; P < 0.001) for the prevalence of PAD and an OR of 1.4 (1.0–1.7, P = 0.039) for the prevalence of myocardial infarction.

CONCLUSIONS

In contrast to previous findings, fetuin-A was higher in type 2 diabetes–PAD patients than in type 2 diabetes–non-PAD patients. In NGM-PAD patients, fetuin-A was also higher than in type 2 diabetes–non-PAD patients. In type 2 diabetes–PAD patients, fetuin-A was inversely associated with mediasclerosis—the calcification process pathognomonic for diabetic PAD. This association persisted in multivariate regression, which is in line with the calcification inhibition in coronary heart or renal disease.
Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine
Authors: Sekhar Rajagopal V. , McKay Siripoom V. , Patel Sanjeet G. , Guthikonda Anuradha P. , Reddy Vasumathi T. , Balasubramanyam Ashok , Jahoor Farook
Published: October 2010

OBJECTIVE

Sustained hyperglycemia is associated with low cellular levels of the antioxidant glutathione (GSH), which leads to tissue damage attributed to oxidative stress. We tested the hypothesis that diminished GSH in adult patients with uncontrolled type 2 diabetes is attributed to decreased synthesis and measured the effect of dietary supplementation with its precursors cysteine and glycine on GSH synthesis rate and oxidative stress.

RESEARCH DESIGN AND METHODS

We infused 12 diabetic patients and 12 nondiabetic control subjects with [2H2]-glycine to measure GSH synthesis. We also measured intracellular GSH concentrations, reactive oxygen metabolites, and lipid peroxides. Diabetic patients were restudied after 2 weeks of dietary supplementation with the GSH precursors cysteine and glycine.

RESULTS

Compared with control subjects, diabetic subjects had significantly higher fasting glucose (5.0 ± 0.1 vs. 10.7 ± 0.5 mmol/l; P < 0.001), lower erythrocyte concentrations of glycine (514.7 ± 33.1 vs. 403.2 ± 18.2 μmol/l; P < 0.01), and cysteine (25.2 ± 1.5 vs. 17.8 ± 1.5 μmol/l; P < 0.01); lower concentrations of GSH (6.75 ± 0.47 vs. 1.65 ± 0.16 μmol/g Hb; P < 0.001); diminished fractional (79.21 ± 5.75 vs. 44.86 ± 2.87%/day; P < 0.001) and absolute (5.26 ± 0.61 vs. 0.74 ± 0.10 μmol/g Hb/day; P < 0.001) GSH synthesis rates; and higher reactive oxygen metabolites (286 ± 10 vs. 403 ± 11 Carratelli units [UCarr]; P < 0.001) and lipid peroxides (2.6 ± 0.4 vs. 10.8 ± 1.2 pg/ml; P < 0.001). Following dietary supplementation in diabetic subjects, GSH synthesis and concentrations increased significantly and plasma oxidative stress and lipid peroxides decreased significantly.

CONCLUSIONS

Patients with uncontrolled type 2 diabetes have severely deficient synthesis of glutathione attributed to limited precursor availability. Dietary supplementation with GSH precursor amino acids can restore GSH synthesis and lower oxidative stress and oxidant damage in the face of persistent hyperglycemia.
Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet
Authors: Salas-Salvadó Jordi , Bulló Monica , Babio Nancy , Martínez-González Miguel Ángel , Ibarrola-Jurado Núria , Basora Josep , Estruch Ramon , Covas Maria Isabel , Corella Dolores , Arós Fernando , Ruiz-Gutiérrez Valentina , Ros Emilio ,   for the PREDIMED Study Investigators
Published: October 2010

OBJECTIVE

To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes.

RESEARCH DESIGN AND METHODS

This was a three-arm randomized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no advice on physical activity was given. The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria.

RESULTS

After a median follow-up of 4.0 years, diabetes incidence was 10.1% (95% CI 5.1–15.1), 11.0% (5.9–16.1), and 17.9% (11.4–24.4) in the MedDiet with olive oil group, the MedDiet with nuts group, and the control group, respectively. Multivariable adjusted hazard ratios of diabetes were 0.49 (0.25–0.97) and 0.48 (0.24–0.96) in the MedDiet supplemented with olive oil and nuts groups, respectively, compared with the control group. When the two MedDiet groups were pooled and compared with the control group, diabetes incidence was reduced by 52% (27–86). In all study arms, increased adherence to the MedDiet was inversely associated with diabetes incidence. Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity.

CONCLUSIONS

MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk.
Repeated Episodes of Hypoglycemia as a Potential Aggravating Factor for Preclinical Atherosclerosis in Subjects With Type 1 Diabetes
Authors: Giménez Marga , Gilabert Rosa , Monteagudo Joan , Alonso Anna , Casamitjana Roser , Paré Carles , Conget Ignacio
Published: October 2010

OBJECTIVE

To evaluate through early preclinical atherosclerosis assessment whether repeated episodes of hypoglycemia represent an aggravating factor for macrovascular disease in type 1 diabetes.

RESEARCH DESIGN AND METHODS

After sample-size calculation, a case-control study of 25 patients with type 1 diabetes and repeated severe/nonsevere hypoglycemia (H-group) compared with 20 age- and sex-matched type 1 diabetes control subjects (C-group) was designed. Assessment of preclinical atherosclerosis consisted of flow-mediated brachial dilatation (FMD) and carotid and femoral intima-media thickness (IMT) studies. To consider hypoglycemia awareness, two different questionnaires and symptomatic response to an acute induction to hypoglycemia were used. Evaluation of the glycemic profile was obtained from continuous glucose monitoring. Endothelial function/inflammation markers were measured in euglycemia/hypoglycemia. A multivariate linear regression analysis was performed to test whether repeated hypoglycemia was independently associated with atherosclerosis.

RESULTS

H-group subjects displayed hypoglycemia unawareness and presented a higher percentage of continuous glucose values and area under the curve <70 mg/dl compared with the C-group (14.2 ± 8.9 vs. 6.3 ± 7.1%, P < 0.02 and 2.4 ± 1.8 vs. 0.6 ± 1.0 mg/dl/day, P < 0.01). The percentage of maximal FMD was lower in the H-group than in the C-group (6.52 ± 2.92 vs. 8.62 ± 3.13%, P < 0.05). A significantly higher IMT was observed at both carotid and femoral sites in the H-group (carotid 0.53 ± 0.09 vs. 0.47 ± 0.08 mm, P < 0.05 and femoral 0.51 ± 0.17 vs. 0.39 ± 0.09 mm, P < 0.05). Baseline inflammation and endothelial function markers were higher in the H-group (leukocytes 7.0 ± 1.8 vs. 5.6 ± 1.4 × 103/ml, von Willebrand factor 119 ± 29 vs. 93 ± 26%, fibrinogen 2.82 ± 0.64 vs. 2.29 ± 0.44g/l, and soluble intercellular adhesion molecule-1 408 ± 224 vs. 296 ± 95 ng/ml; P < 0.05 for all).

CONCLUSIONS

In addition to the induction of hypoglycemia unawareness and an increased risk for severe hypoglycemia, repeated hypoglycemia could be related to and considered an aggravating factor for preclinical atherosclerosis in type 1 diabetes. The precise mechanisms explaining this association remain to be clarified.
Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily or Other Glucose-Lowering Therapies
Authors: Best Jennie H. , Hoogwerf Byron J. , Herman William H. , Pelletier Elise M. , Smith Daniel B. , Wenten Made , Hussein Mohamed A.
Published: October 2010

OBJECTIVE

To test the hypothesis that exenatide twice daily reduces the relative incidence of cardiovascular disease (CVD) events among patients with type 2 diabetes compared with other glucose-lowering agent(s).

RESEARCH DESIGN AND METHODS

A retrospective database analysis was performed of the LifeLink database of medical and pharmaceutical insurance claims for June 2005 through March 2009. Patients with no history in the preceding 9 months of myocardial infarction, ischemic stroke, or coronary revascularization procedure were assigned to the exenatide-initiated or non–exenatide-initiated cohorts based on the first new prescription filled and reassigned if exenatide was prescribed or discontinued. Incident CVD events (myocardial infarction, ischemic stroke, or coronary revascularization procedure) were identified by ICD-9-CM diagnosis codes. Patient outcomes were adjusted for differences in clinical and demographic characteristics and compared using propensity score–weighted discrete time survival analysis with time-varying exposure to exenatide.

RESULTS

A total of 39,275 patients with type 2 diabetes were treated with exenatide twice daily, and 381,218 patients were treated with other glucose-lowering therapies. Patients who initiated exenatide were more likely to have prior ischemic heart disease, obesity, hyperlipidemia, hypertension, and/or other comorbidities at baseline. Exenatide-treated patients were less likely to have a CVD event than non–exenatide-treated patients (hazard ratio 0.81; 95% CI 0.68–0.95; P = 0.01) and lower rates of CVD-related hospitalization (0.88; 0.79–0.98; P = 0.02) and all-cause hospitalization (0.94; 0.91–0.97; P < 0.001).

CONCLUSIONS

Exenatide twice-daily treatment was associated with a lower risk of CVD events and hospitalizations than treatment with other glucose-lowering therapies.
Human Enterovirus RNA in Monthly Fecal Samples and Islet Autoimmunity in Norwegian Children With High Genetic Risk for Type 1 Diabetes
Authors: Tapia German , Cinek Ondrej , Rasmussen Trond , Witsø Elisabet , Grinde Bjørn , Stene Lars Christian , Rønningen Kjersti Skjold
Published: October 2010

OBJECTIVE

To test whether the frequency of human enterovirus RNA in fecal samples collected monthly from early infancy was associated with development of multiple islet autoantibodies in children with the highest risk HLA genotype.

RESEARCH DESIGN AND METHODS

Individuals carrying the HLA DRB1*0401-DQA1*03-DQB1*0302/DRB1*03-DQA1*05-DQB1*02 genotype were identified at birth and followed with monthly stool samples from age 3 to 35 months. Blood samples taken at age 3, 6, 9, and 12 months and then annually were tested for autoantibodies to insulin, GAD 65 and IA-2. Among 911 children, 27 developed positivity for two or more islet autoantibodies in two or more consecutive samples (case subjects). Two control subjects per case subject were matched by follow-up time, date of birth, and county of residence. Stool samples were analyzed for enterovirus with a semiquantitative real-time RT-PCR.

RESULTS

The frequency of human enterovirus RNA in stool samples from case subjects before seroconversion (43 of 339, 12.7%) did not differ from the frequency in control subjects (94 of 692, 13.6%) (P = 0.97). Results remained essentially unchanged after adjustment for potential confounders, restriction to various time windows before seroconversion, or infections in the 1st year of life or after inclusion of samples collected after seroconversion. There was no difference in the average quantity of enterovirus RNA or in the frequency of repeatedly positive samples. The estimated relative risk for islet autoimmunity per enterovirus RNA–positive sample during follow-up (nested case-control analysis) was 1.12 (95% CI 0.66–1.91).

CONCLUSIONS

There was no support for the hypothesis that fecal shedding of enteroviral RNA is a major predictor of advanced islet autoimmunity.
Determinants of Social Participation—With Friends and Others Who Are Not Family Members—for Youths With Cerebral Palsy
Authors: Kang Lin-Ju , Palisano Robert J. , Orlin Margo N. , Chiarello Lisa A. , King Gillian A. , Polansky Marcia
Published: October 2010

Background

Social participation provides youths with opportunities to develop their self-concept, friendships, and meaning in life. Youths with cerebral palsy (CP) have been reported to participate more in home-based leisure activities and to have fewer social experiences with friends and others than youths without disabilities.

Objective

The objective of this study was to identify youth, family, and service determinants of the participation of youths with CP in leisure activities with friends and others who are not family members.

Design

The study design was a cross-sectional analysis.

Methods

The participants were 209 youths who were 13 to 21 years old (52% male), had CP, and were classified in Gross Motor Function Classification System (GMFCS) levels I to V as well as their parents. The participants were recruited from 7 children's hospitals in 6 different states. Youths completed the Children's Assessment of Participation and Enjoyment in structured interviews. Parents completed the Coping Inventory, Pediatric Outcomes Data Collection Instrument, Family Environment Scale, Measure of Processes of Care, and demographic and service questionnaires. Researchers determined GMFCS levels. A sequential multiple regression analysis was used to determine the youth, family, and service variables that predicted participation with friends and with others who were not family members.

Results

Sports and physical function, communication or speech problems, educational program, and the extent to which the desired community recreational activities were obtained explained 45.8% of the variance in the number of activities engaged in with friends. A higher level of parental education explained 6.3% of the variance in the number of activities engaged in with others who were not family members.

Limitations

The youths' activity preferences and intensity of participation were not examined.

Conclusions

Youth and service characteristics were determinants of participation with friends but not others who were not family members. The findings have implications for the role of physical therapists in promoting sports and physical and communication abilities and enhancing community opportunities to optimize the social participation of youths with CP.
How short are ultra short light pulses? (looking back to the mid sixties)
Authors: Weber H. P. , Dändliker R.
Published: October 2010

With the arrival of mode locking for Q-switched lasers to generate ultra short light pulses, a method to measure their expected time duration in the psec range was needed. A novel method, based on an intensity correlation measurement using optical second harmonic generation, was developed. Other reported approaches for the same purpose were critically analysed. Theoretical and subsequent experimental studies lead to surprising new insight into the ultra fast temporal behaviour of broadband laser radiation: any non mode locked multimode emission of a laser consists of random intensity fluctuations with duration of the total inverse band width of emitted radiation. However, it was shown, that with mode locking isolated ultra short pulses of psec duration can be generated. This article summarizes activities performed in the mid sixties at the University of Berne, Switzerland.
On the Thompson-Wolf experiment: a study with laser sources
Authors: Barato David Paredes , Calvo Maria L.
Published: October 2010

We present a revisited study of the Thompson-Wolf experiment earlier developed in 1957 with the aim to characterize the degree of spatial coherent of a luminous source. We develop further experiments by using laser sources under various modal regimes. We analyze the experimental results.
A Gaussian transition of an optical speckle field studied by the minimal spanning tree method
Authors: Vasseur Olivier , Bergoënd Isabelle , Orlik Xavier
Published: October 2010

We propose to study the Gaussian transition of an optical speckle field using the Minimal Spanning Tree method. We perform an analysis of the spatial intensity distribution and show that the maxima of intensity evolve from a cluster distribution in the strongly non Gaussian regime, to a gradient distribution around the transition and then approach the random distribution area when we tend to the Gaussian regime. In the generated minimal spanning trees, we observe that the standard deviation of the edges length exhibits a maximum around the Gaussian transition when about 4 correlation cells of the surface roughness are illuminated.
Investigations on a robust profile model for the reconstruction of 2D periodic absorber lines in scatterometry
Authors: Gross H. , Richter J. , Rathsfeld A. , Bär M.
Published: October 2010

Scatterometry as a non-imaging indirect optical method in wafer metrology is applicable to lithography masks designed for extreme ultraviolet (EUV) lithography, where light with wavelengths of about 13.5 nm is applied. The main goal is to reconstruct the critical dimensions (CD) of the mask, i.e., profile parameters such as line width, line height, and side-wall angle, from the measured diffracted light pattern and to estimate the associated uncertainties. The numerical simulation of the diffraction process for periodic 2D structures can be realized by the finite element solution of the two-dimensional Helmholtz equation. The inverse problem is expressed as a non-linear operator equation where the operator maps the sought mask parameters to the efficiencies of the diffracted plane wave modes. To solve this operator equation, the deviation of the measured efficiencies from the ones obtained computationally is minimized by a Gauß-Newton type iterative method. In the present paper, the admissibility of rectangular profile models for the evaluations of CD uniformity is studied. More precisely, several sets of typical measurement data are simulated for trapezoidal shaped EUV masks with different mask signatures characterized by various line widths, heights and side-wall angles slightly smaller than 90°. Using these sets, but assuming rectangular structures as the basic profiles of the numerical reconstruction algorithm, approximate line height and width parameters are determined as the critical dimensions of the mask. Finally, the model error due to the simplified shapes is analyzed by checking the deviations of the reconstructed parameters from their nominal values.
Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy
Authors: Champaneria Rita , Abedin Parveen , Daniels Jane , Balogun Moji , Khan Khalid S.
Published: October 2010

Background. Adenomyosis is a common condition that causes substantial morbidity. Until recently, the reference standard for a definitive diagnosis was histology of hysterectomy specimens. Ultrasound and magnetic resonance imaging (MRI) may allow accurate non‐invasive diagnosis. Objective. To compare the diagnostic accuracy of these techniques. Design. Systematic review with meta‐analysis. Population. Women who had ultrasound and/or MRI, and whose results were compared with a reference standard. Methods. Electronic searches were conducted in literature databases from database inception to 2010. The reference lists of known relevant articles were searched for further articles. Selected studies reported data on ultrasound and/or MRI with histological confirmation of diagnosis. Two reviewers independently selected articles without language restrictions, and extracted data in the form of 2 × 2 tables. We computed sensitivity and specificity for individual studies and pooled these results in a meta‐analysis. We also performed meta‐regression to examine how the index tests compared on diagnostic accuracy. Results. Twenty‐three articles (involving 2,312 women) satisfied the inclusion criteria. Transvaginal ultrasound had a pooled sensitivity of 72% (95% CI 65–79%), specificity of 81% (95% CI 77–85%), positive likelihood ratio of 3.7 (95% CI 2.1–6.4) and negative likelihood ratio of 0.3 (95% CI 0.1–0.5). MRI had a pooled sensitivity of 77% (95% CI 67–85%), specificity of 89% (95% CI 84–92%), positive likelihood ratio of 6.5 (95% CI 4.5–9.3), and negative likelihood ratio of 0.2 (95% CI 0.1–0.4). The results show that a correct diagnosis was obtained more often with MRI. Conclusion. Transvaginal ultrasound and MRI show high levels of accuracy for the non‐invasive diagnosis of adenomyosis.