bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacations to Waterside Locations Result in Nevus Development in Colorado Children
Authors: Pettijohn Kelly J. , Asdigian Nancy L. , Aalborg Jenny , Morelli Joseph G. , Mokrohisky Stefan T. , Dellavalle Robert P. , Crane Lori A.
Published: February 2009

Nevi are a main risk factor for malignant melanoma, and most nevi develop in childhood. This study examined the relationship between vacations and nevi in 681 White children born in 1998 who were lifetime residents of Colorado. Vacation histories were assessed through telephone interviews of parents, whereas nevus and phenotypic characteristics were assessed through skin exams at age 7. Multiple linear and logistic regression were used to assess the influence of vacations on counts of nevi <2 mm in size and the presence of any nevi ≥2 mm after controlling for other variables. Each waterside vacation ≥1 year before the exam at age 7 was found to be associated with a 5% increase in nevi <2 mm. Waterside vacations <1 year before the skin exam were not related to nevus count (<2 mm); regardless of timeframe, waterside vacations were not related to the presence of nevi ≥2 mm. UV dose received on waterside vacations, number of days spent on waterside vacations, and nonwaterside vacations were not significantly related to nevi <2 or ≥2 mm. These results suggest that there is a lag of at least 1 year in the development of new nevi after vacation sun exposure. It appears that a threshold dose of UV exposure is received quickly on each waterside vacation. Parents of young children should exercise caution in selection of vacation locations to reduce melanoma risk. (Cancer Epidemiol Biomarkers Prev 2009;18(2):454–63)
Genetic Variation in the Androgen Receptor Gene and Endometrial Cancer Risk
Authors: Yang Hannah P. , Garcia-Closas Montserrat , Lacey James V. , Brinton Louise A. , Lissowska Jolanta , Peplonska Beta , Chanock Stephen , Gaudet Mia M.
Published: February 2009

Genetic variation in the androgen receptor (AR) gene may be associated with endometrial cancer risk based on the role of AR in regulating androgen levels. However, endometrial cancer studies reported inconsistent associations for a CAG repeat polymorphism in exon 1. Only one of these studies measured haplotype-tagging single nucleotide polymorphisms (htSNP) in AR and found statistically nonsignificant, decreased associations with endometrial cancer risk. In a population-based case-control study of 497 cases and 1,024 controls, we examined the CAG repeat polymorphism and six htSNPs (rs962458, rs6152, rs1204038, rs2361634, rs1337080, and rs1337082), which cover an estimated 80% of the known common variation in AR among Caucasian populations. CAG repeat length was not significantly associated with endometrial cancer [odds ratio per unit increase in the average number of repeats, 1.02 (95% confidence interval, 0.97-1.08); Ptrend = 0.29]. Minor alleles in three correlated htSNPs (rs6152, rs1204038, and rs1337082; r2 >0.6) were associated with increased risk for endometrial cancer. The strongest association was observed for rs6152, with the odds ratios (95% confidence interval) being 1.13 (0.89-1.44) for heterozygous and 2.40 (1.28-4.51) for homozygous minor genotypes (Ptrend = 0.02) compared with homozygous major allele genotype. However, these associations were not statistically significant after permutation adjustment for multiple comparisons (Ptrend > 0.09). Haplotype analyses did not reveal any additional associations with endometrial cancer. Results from our study, taken together with previously published studies, provide little evidence of a consistent association between common genetic variation in AR and endometrial cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(2):585–9)
Meta Association of Colorectal Cancer Confirms Risk Alleles at 8q24 and 18q21
Authors: Curtin Karen , Lin Wei-Yu , George Rina , Katory Mark , Shorto Jennifer , Cannon-Albright Lisa A. , Bishop D. Timothy , Cox Angela , Camp Nicola J. ,   Colorectal Cancer Study Group
Published: February 2009

Background: Genome-wide association studies of colorectal cancer (CRC) have identified genetic variants that reproducibly associate with CRC. Associations of 12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 (SMAD7) and CRC were investigated in a three-center collaborative study including two U.K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees.

Methods: Our combined resource included 1,092 CRC case subjects and 1,060 age- and sex-matched controls. Meta statistics and Monte Carlo significance testing using Genie software provided a valid combined analysis of our mixed independent and related case-control resource. We also evaluated whether these associations differed by sex, age at diagnosis, family history, or tumor site.

Results: At 8q24, we observed two independent significant associations at single nucleotide polymorphisms located in two different risk regions of 8q24: rs6983267 in region 3 [Ptrend = 0.01; per allele odds ratio (OR), 1.17; 95% confidence intervals (95% CI), 1.03-1.32] and rs10090154 in region 5 (Ptrend = 0.05; per allele OR, 1.24; 95% CI, 1.01-1.51). At 18q21, associations were observed in distal colon tumors but not in proximal or rectal cancers: rs4939827 (Ptrend = 0.007; per allele OR, 0.77; 95% CI, 0.64-0.93; case-case pdiff = 0.03) and rs12953717 (Ptrend = 0.01; per allele OR, 1.27; 95% CI, 1.06-1.52). We were unable to detect any associations at 9p24 with CRC.

Conclusions: Our investigation confirms that variants across multiple risk regions of 8q24 are associated with CRC, and that associations at 18q21 differ by tumor site. (Cancer Epidemiol Biomarkers Prev 2009;18(2):616–21)
Overexpression of EIF-5A2 Is an Independent Predictor of Outcome in Patients of Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy
Authors: Chen Wei , Luo Jun-Hang , Hua Wen-Feng , Zhou Fang-Jian , Lin Marie C. , Kung Hsiang-Fu , Zeng Yi-Xin , Guan Xin-Yuan , Xie Dan
Published: February 2009

Background: Our previous study has suggested an oncogenic role of eIF-5A2 in ovarian tumorigenesis. Abnormalities of eIF-5A2 and its clinical/prognostic significance, however, in urothelial carcinoma of the bladder (UC) are unclear.

Methods: In this study, the methods of reverse transcription-PCR, immunohistochemistry, and fluorescence in situ hybridization were used to examine mRNA/protein expression and amplification of eIF-5A2 in a large cohort of UCs treated with radical cystectomy.

Results: Up-regulated expression of eIF-5A2 mRNA was observed in 50% (8 of 16) of UCs, when compared with adjacent normal bladder tissues. Overexpression of EIF-5A2 protein and amplification of eIF-5A2 was examined informatively in 45.3% (39 of 86) and 10.6% (5 of 47) of UCs, respectively. In univariate survival analysis of the UC cohorts, a significant association of overexpression of EIF-5A2 with shortened patient survival (mean, 38.2 months versus 52.9 months, P = 0.001, log-rank test) was shown. In different subsets of UC patients, overexpression of EIF-5A2 was also a prognostic indicator in grade 1/2 (P = 0.0009) and grade 3 (P = 0.016) tumor patients, and in pT1 (P = 0.0089), pT2 (P = 0.0354), pT3/4 (P = 0.0058), pN0 (P = 0.0039), and pN1-2 (P = 0.0093) tumor patients. Importantly, EIF-5A2 expression (P = 0.0007) together with pT stage (P = 0.0001) provided significant independent prognostic variables in multivariate analysis.

Conclusions: These findings indicate that overexpression of EIF-5A2 in UCs is coincident with acquisition of a poor prognostic phenotype, suggesting that the expression of EIF-5A2, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of UC patients treated with radical cystectomy. (Cancer Epidemiol Biomarkers Prev 2009;18(2):400–8)
Longitudinal Biological Exposure to Carotenoids Is Associated with Breast Cancer–Free Survival in the Women's Healthy Eating and Living Study
Authors: Rock Cheryl L. , Natarajan Loki , Pu Minya , Thomson Cynthia A. , Flatt Shirley W. , Caan Bette J. , Gold Ellen B. , Al-Delaimy Wael K. , Newman Vicky A. , Hajek Richard A. , Stefanick Marcia L. , Pierce John P. ,   for the Women's Healthy Eating and Living Study Group
Published: February 2009

In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer–free survival in the Women's Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer–free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer–free survival regardless of study group assignment. (Cancer Epidemiol Biomarkers Prev 2009;18(2):486–94)
Assessment of Lifetime Cumulative Sun Exposure Using a Self-Administered Questionnaire: Reliability of Two Approaches
Authors: Yu Chu-Ling , Li Yan , Freedman D. Michal , Fears Thomas R. , Kwok Richard , Chodick Gabriel , Alexander Bruce , Kimlin Michael G. , Kricker Anne , Armstrong Bruce K. , Linet Martha S.
Published: February 2009

Few studies have evaluated the reliability of lifetime sun exposure estimated from inquiring about the number of hours people spent outdoors in a given period on a typical weekday or weekend day (the time-based approach). Some investigations have suggested that women have a particularly difficult task in estimating time outdoors in adulthood due to their family and occupational roles. We hypothesized that people might gain additional memory cues and estimate lifetime hours spent outdoors more reliably if asked about time spent outdoors according to specific activities (an activity-based approach). Using self-administered, mailed questionnaires, test-retest responses to time-based and to activity-based approaches were evaluated in 124 volunteer radiologic technologist participants from the United States: 64 females and 60 males 48 to 80 years of age. Intraclass correlation coefficients (ICC) were used to evaluate the test-retest reliability of average number of hours spent outdoors in the summer estimated for each approach. We tested the differences between the two ICCs, corresponding to each approach, using a t test with the variance of the difference estimated by the jackknife method. During childhood and adolescence, the two approaches gave similar ICCs for average numbers of hours spent outdoors in the summer. By contrast, compared with the time-based approach, the activity-based approach showed significantly higher ICCs during adult ages (0.69 versus 0.43, P = 0.003) and over the lifetime (0.69 versus 0.52, P = 0.05); the higher ICCs for the activity-based questionnaire were primarily derived from the results for females. Research is needed to further improve the activity-based questionnaire approach for long-term sun exposure assessment. (Cancer Epidemiol Biomarkers Prev 2009;18(2):464–71)
Rad50 c.687delT Does Not Contribute Significantly to Familial Breast Cancer in a French Population
Authors: Uhrhammer Nancy , Delort Laetitia , Bignon Yves-Jean
Published: February 2009

Mutations in DNA repair genes are known for their association with hereditary breast cancer. BRCA1 and BRCA2 are the major genes for high-penetrance familial breast and ovarian cancer, whereas mutations in ATM or Chek2 confer more modest cancer risk. Additional genes involved in DNA double-strand break repair have more recently been associated with breast cancer risk: heterozygosity for deleterious mutations in components of the Rad50-Mre11-Nbs1 complex seems to predispose to breast cancer. In particular, the c.687delT mutation in Rad50 conferred an odds ratio of 4.3 for the risk of breast cancer in a study of Finnish breast cancer families. To explore the contribution of this mutation to breast cancer in French families for which no BRCA mutation could be found, we analyzed the relevant exon in 618 familial breast cancer cases and 513 controls with no personal or familial history of breast cancer. Rad50 was analyzed in its entirety for 231 familial cases, with no clearly deleterious mutations detected. These data together suggest that although founder mutations may make Rad50 a significant breast cancer risk factor in certain populations, it is not a factor in others. (Cancer Epidemiol Biomarkers Prev 2009;18(2):684–5)
Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation
Authors: Bang Soo-Mee , Lee Jong-Seok , Ahn Jeong Yeal , Lee Jae Hoon , Hyun Myung Soo , Kim Bong Seog , Park Moo Rim , Kim Ho Young , Kim Hyo Jung , Lee Moon Hee , Kim Hwak , Won Jong Ho , Yoon Hwi Joong , Oh Do-yeun , Nam Eun-Mi , Bae Sung Hwa , Kim Byoung-Kook , Chi Hyun-Sook ,   for the Korean MPN Working Party
Published: February 2009

Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients’ diagnoses were essential thrombocythemia (ET n=146), polycythemia vera (PV n=120), primary myelofibrosis (n=12), and unclassifiable MPN (MPNu n=5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p=0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p=0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.
How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation?
Authors: Rietbrock Stephan , Plumb Jonathan M. , Gallagher Arlene M. , van Staa Tjeerd P.
Published: February 2009

The objective of this study was to evaluate the rate of stroke associated with aspirin and warfarin in routine clinical practice. The study included patients aged 40+ with chronic atrial fibrillation (cAF) registered in the UK General Practice Research Database. The outcome was the rate of stroke during current, past and no use of aspirin and warfarin. The study included 51,807 cAF patients. There was no difference in the rate of stroke between current and past use of aspirin (relative rate [RR]=1.04 [95% confidence interval (CI) 0.94 – 1.15]), while the rate of stroke was reduced during current warfarin use compared to past use (RR=0.62 [95% CI 0.54 – 0.71]). For warfarin, a pattern of lower rates of stroke during current exposure and higher rates with past exposure was seen only in patients treated for at least 6–12 months. For aspirin, no changes in the rates of stroke were observed with discontinuation of aspirin. The effectiveness of warfarin was dependent on the level of anticoagulation, with optimal risk reduction occurring within the recommended international normalised ratio (INR) range of 2.0 to 3.0. The proportion of patients achieving a stable INR within the target therapeutic range was at its lowest during the first three months of warfarin treatment. In conclusion, the results of this study support the effectiveness of warfarin treatment to reduce the rate of stroke in cAF patients in the general clinical practice setting, however the risk reduction is lower than that reported in clinical trials.
Thrombin inhibits nuclear factor κB and RhoA pathways in cytokine-stimulated vascular endothelial cells when EPCR is occupied by protein C
Authors: Bae Jong-Sup , Rezaie Alireza R.
Published: February 2009

The occupancy of endothelial protein C receptor (EPCR) by protein C switches the protease activated receptor 1 (PAR-1)-dependent signalling specificity of thrombin from a permeability enhancing to a barrier protective response in vascular endothelial cells. In this study, the modulatory effects of thrombin and thrombin receptor agonist peptides (TRAP) on tumour necrosis factor (TNF)-α-stimulated HUVECs in the absence and presence of the catalytically inactive protein C-S195A were evaluated by monitoring the expression of cell surface adhesion molecules (VCAM-1, ICAM-1 and E-selectin), adhesion of freshly isolated neutrophils to cytokine-stimulated endothelial cells, regulation of the Rho family of small GTPases and the activation of nuclear factor-κB (NF-κB) pathway. The analysis of results indicate that both thrombin and TRAP initiate proinflammatory responses in endothelial cells, thus neither PAR-1 agonist in-fluenced the proinflammatory effects of TNF-α in the absence of the protein C mutant. Interestingly, however, the occupancy of EPCR by the protein C mutant switched the PAR-1-dependent signaling specificity of thrombin, thus leading to thrombin inhibition of the expression of all three adhesion molecules as well as the binding of neutrophils to TNF-α-activated endothelial cells. Furthermore, similar to activated protein C, both thrombin and TRAP activated Rac1 and inhibited the activation of RhoA and NF-κB pathways in response to TNF-α in cells pre-treated with protein C-S195A. Based on these results we conclude that when EPCR is ligated by protein C, the cleavage of PAR-1 by thrombin initiates antiinflammatory responses, thus leading to activation of Rac1 and inhibition of RhoA and NF-κB signalling cascades in vascular endothelial cells.
Relationship between exercise capacity, endothelial progenitor cells and cytochemokines in patients undergoing cardiac rehabilitation
Authors: Sofi Francesco , Caporale Roberto , Capalbo Andrea , Marcucci Rossella , Macchi Claudio , Lova Raffaele Molino , Cellai Tommaso , Vannucci Mauro , Gensini Gian Franco , Abbate Rosanna , Gori Anna Maria , Cesari Francesca
Published: February 2009

No data are available about the possible role of endothelial progenitor cells (EPCs), cytochemokines and N-terminal pro-brain natriuretic peptide (NT-proBNP) in determining a different response to short period of cardiologic rehabilitation (CR), as measured by the improvement of exercise capacity. In a population of 86 cardiac surgery patients, we evaluated the numbers of EPCs, pro- and anti-inflammatory cytokines (IL-6,IL-8, IL-10, IL-1ra), hs-C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and NT-proBNP before (T1), and after 15 days of CR (T2). EPCs were measured by flow cytometry, and the exercise capacity was measured at T1 and T2 by using the six-minute walk test (6MWT). At T2, a significant increase of 6MWT (p<0.0001) was detected. No significant increase of EPCs was observed, while a significant (at least p<0.05) decrease in cytochemokines, CRP and NT-ProBNP levels was evidenced. By analyzing the median improvement of 6MWT, only patients with a median improvement ≥23% showed a significant (p<0.05) increase of EPCs at T2, with significant correlations between EPCs, VEGF and IL-10. On the contrary, in patients with a median improvement <23% a negative correlation between CRP and EPCs was observed. Finally, CD34+/KDR+ EPCs showed significant correlation with IL-8 at T1. In conclusion, a short period of CR intervention determines a different pattern of modifications for EPCs in relation to the improvement of exercise capacity.
A multicentre randomised assessment of the DAWN AC computer-assisted oral anticoagulant dosage program
Authors: Keown Michelle , Ibrahim Saied , Lowe Gordon , Moia Marco , Turpie Alexander G. , Roberts Christopher , van den Besselaar Anton M. H. P. , van der Meer Felix J. M. , Tripodi Armando , Palareti Gualtiero , Shiach Caroline , Bryan Stirling , Samama Meyer , Burgess-Wilson Michael , Heagerty Anthony , MacCallum Peter , Wright David , Jespersen Jørgen , Poller Leon ,   European Action on Anticoagulation (EAA)
Published: February 2009

Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of “time in target INR range” (TIR) not on clinical safety in practice. A five-year international randomised clinical study of computer assistance with the DAWN AC program compared with manual dosage in 2,631 patients has been performed at 13 centres with established expertise in oral anticoagulation mainly in the EU. Safety assessment have been based on the comparison of bleeding or thrombotic events with DAWN AC compared with manual dosage in a randomised study. Safety of the DAWN AC program has been demonstrated. Clinical events of bleeding and thrombosis were almost identical with the experienced manual dosage group. Therapeutic control improved with DAWN AC to 66.8% from 63.4% TIR. The program failed to provide a dosage recommendation on only 5.7% of occasions. At a group of experienced centres with a special interest in oral anticoagulation, the DAWN AC computer-dosage program proved as safe clinically as manual dosage by experienced medical staff. With DAWN AC, laboratory control was improved, the difference being highly significant. The results should reassure hospitals and community clinics that the DAWN AC program is safe and facilitate greater and longer provision of warfarin treatment where required.
Cardiac Resynchronization Therapy Reduces the Risk of Hospitalizations in Patients With Advanced Heart Failure
Authors: Anand Inder S. , Carson Peter , Galle Elizabeth , Song Rui , Boehmer John , Ghali Jalal K. , Jaski Brian , Lindenfeld JoAnn , O'Connor Christopher , Steinberg Jonathan S. , Leigh Jill , Yong Patrick , Kosorok Michael R. , Feldman Arthur M. , DeMets David , Bristow Michael R.
Published: February 2009

Background—

In the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial, 1520 patients with advanced heart failure were assigned in a 1:2:2 ratio to optimal pharmacological therapy or optimal pharmacological therapy plus cardiac resynchronization therapy (CRT-P) or CRT with defibrillator (CRT-D). Use of CRT-P and CRT-D was associated with a significant reduction in combined risk of death or all-cause hospitalizations. Because mortality also was significantly reduced (optimal pharmacological therapy versus CRT-D only), an assessment of the true reduction in hospitalization rates must consider the competing risk of death and varying follow-up times.

Methods and Results—

To overcome the challenges of comparing treatment groups, we used a nonparametric test of right-censored recurrent events that accounts for multiple hospital admissions, differential follow-up time between treatment groups, and death as a competing risk. An end-point committee adjudicated and classified all hospitalizations. Compared with optimal pharmacological therapy, CRT-P and CRT-D were associated with a 21% and 25% reduction in all-cause, 34% and 37% reduction in cardiac, and 44% and 41% reduction in heart failure hospital admissions per patient-year of follow-up, respectively. Similar reductions were seen in hospitalization days per patient-year. The reduction in hospitalization rate for heart failure in the CRT groups appeared within days of randomization and remained sustained. Noncardiac hospitalization rates were not different between groups.

Conclusion—

Use of CRT with or without a defibrillator in advanced heart failure patients was associated with marked reductions in all-cause, cardiac, and heart failure hospitalization rates in an analysis that accounted for the competing risk of mortality and unequal follow-up time.
Antiplatelet Therapy and Stent Thrombosis After Sirolimus-Eluting Stent Implantation
Authors: Kimura Takeshi , Morimoto Takeshi , Nakagawa Yoshihisa , Tamura Toshihiro , Kadota Kazushige , Yasumoto Hitoshi , Nishikawa Hideo , Hiasa Yoshikazu , Muramatsu Toshiya , Meguro Taiichiro , Inoue Naoto , Honda Hidehiko , Hayashi Yasuhiko , Miyazaki Shunichi , Oshima Shigeru , Honda Takashi , Shiode Nobuo , Namura Masanobu , Sone Takahito , Nobuyoshi Masakiyo , Kita Toru , Mitsudo Kazuaki
Published: February 2009

Background—

The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately.

Methods and Results—

In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%,
P
<0.001; 0.72% versus 0.07%,
P
=0.02; and 2.1% versus 0.14%,
P
=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (
P
=0.99) in the 6-month landmark analysis.

Conclusions—

Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.
Systemic Arterial Response to Exercise in Patients With Aortic Valve Stenosis
Authors: Laskey Warren K. , Kussmaul William G. , Noordergraaf Abraham
Published: February 2009

Background—

Systemic arterial hemodynamics play an important role in the assessment of the severity and hemodynamic consequences of aortic valve stenosis (AVS).

Methods and Results—

Systemic vascular resistance, total arterial compliance, effective arterial elastance, and aortic characteristic impedance were derived from high-fidelity catheter recordings of ascending aortic pressure and blood flow velocity at rest and with supine bicycle exercise in 18 patients with AVS and 11 control subjects. Mean aortic pressure was similar between groups. At rest, systemic vascular resistance (AVS patients, 1426±318 dynes · s · cm
−5
; control subjects, 107±228 dynes · s · cm
−5
;
P
<0.01), arterial elastance (AVS patients, 1.38±0.36 mm Hg/mL; control subject, 0.99±0.15 mm Hg/mL;
P
<0.002), and aortic characteristic impedance (AVS patients, 107±23 dynes · s · cm
−5
; control subjects, 76±30 dynes · s · cm
−5
;
P
<0.01) were increased, whereas total arterial compliance was lower (AVS patients, 0.737±0.19×10
−3
cm
5
/dyne; control subjects, 1.155±0.27×10
−3
cm
5
/dyne;
P
<0.001) in AVS. With exercise, total arterial compliance increased in control subjects (rest, 1.155±0.27×10
−3
cm
5
/dyne; exercise, 1.421±0.49×10
−3
cm
5
/dyne;
P
<0.05) but did not change in AVS patients (rest, 0.737±0.19×10
−3
cm
5
/dyne; exercise, 0.769±0.21×10
−3
cm
5
/dyne;
P
=0.2). Arterial elastance increased on exercise in AVS patients (rest, 1.38±0.36 mm Hg/mL; exercise, 1.57±0.44;
P
<0.01). Aortic characteristic impedance remained elevated on exercise (AVS patients, 122±30 dynes · s · cm
−5
; control subjects, 80±43 dynes · s · cm
−5
;
P
=0.01). Stroke flow increased significantly in both AVS patients (rest, 229±69 mL/s; exercise, 256±78 mL/s;
P
<0.01) and control subjects (rest, 230±37 mL/s; exercise, 406±69 mL/s;
P
<0.001), although the increment was much attenuated in AVS. On multiple regression, the increase in stroke flow was related to the decrease in systemic vascular resistance (
P
=0.03), increase in total arterial compliance (
P
=0.03), and decrease in arterial elastance (
P
=0.02).

Conclusions—

These results indicate a pressure-independent increase in the steady and pulsatile components of the arterial load in patients with AVS under resting conditions. Persistent “stiffening” of the arterial system is an important contributor to the diminished stroke output response to exercise in AVS.
Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension
Authors: Nagae Ai , Fujita Megumi , Kawarazaki Hiroo , Matsui Hiromitsu , Ando Katsuyuki , Fujita Toshiro
Published: February 2009

Background—

Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate central sympathoexcitation in the initial stage of obesity-induced hypertension.

Methods and Results—

Four-week-old male Sprague-Dawley rats were fed a high-fat (45% kcal as fat) or low-fat (10% kcal as fat) diet for 6 weeks. Fat loading elicited hypertension and sympathoexcitation, along with visceral obesity. In urethane-anesthetized and artificially ventilated rats, arterial pressure and renal sympathetic nerve activity decreased in a dose-dependent fashion when 53 or 105 μmol/kg tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. Central tempol reduced arterial pressure and renal sympathetic nerve activity to a significantly greater extent in high-fat diet–fed hypertensive rats than in low-fat diet–fed normotensive rats. Intracerebroventricular apocynin or diphenyleneiodonium, a reduced NADPH oxidase inhibitor, also elicited markedly greater reductions in arterial pressure and renal sympathetic nerve activity in the high-fat diet–fed rats. In addition, fat loading increased NADPH oxidase activity and NADPH oxidase subunit p22
phox
, p47
phox
, and gp91
phox
mRNA expression in the hypothalamus.

Conclusions—

In obesity-induced hypertension, increased oxidative stress in the brain, possibly via activation of NADPH oxidase, may contribute to the progression of hypertension through central sympathoexcitation.
Immediate and Sustained Blood Pressure Lowering by Urocortin 2
Authors: Dieterle Thomas , Meili-Butz Silvia , Bühler Katrin , Morandi Christian , John Dietlinde , Buser Peter T. , Rivier Jean , Vale Wylie W. , Peterson Kirk L. , Brink Marijke
Published: February 2009

Recently, novel corticotropin-releasing factor-related peptides, named urocortin 1, 2, and 3, and a distinct cardiac and peripheral vascular receptor (corticotropin-releasing factor receptor 2) were described being part of a peripheral corticotropin-releasing factor system modulating cardiovascular function in response to stress. Vasorelaxation and blood pressure lowering have been reported after acute administration of these peptides. No data are available on the acute and chronic effects of urocortin 2 on blood pressure in models of arterial hypertension. To test these effects, hypertensive salt-sensitive and normotensive salt-resistant Dahl rats were randomly assigned to twice-daily applications of urocortin 2 or vehicle for 5 weeks. Blood pressure, heart rate, and left ventricular dimension and function were recorded at baseline, after initial application, and, together with cardiac and aortic expression of urocortin 2 and its receptor, after 5 weeks of treatment. Urocortin 2 significantly reduced blood pressure in hypertensive rats without affecting heart rate. Long-term urocortin 2 treatment in hypertensive rats induced sustained blood pressure reduction and diminished the development of hypertension-induced left ventricular hypertrophy and the deterioration of left ventricular contractile function. Corticotropin-releasing factor receptor 2 expression was preserved despite chronic stimulation by urocortin 2. In conclusion, our study shows that, in an animal model of arterial hypertension, urocortin 2 has immediate and sustained blood pressure–lowering effects. Beneficial effects on blood pressure, left ventricular dimension, and function, together with preserved receptor expression, suggest that corticotropin-releasing factor receptor 2 stimulation by urocortin 2 may represent a novel approach to the treatment of arterial hypertension.
Reinterpreting No Free Lunch
Authors: Rowe Jon E. , Vose M. D. , Wright Alden H.
Published: February 2009

Since its inception, the “No Free Lunch” theorem (NFL) has concerned the application of symmetry results rather than the symmetries themselves. In our view, the conflation of result and application obscures the simplicity, generality, and power of the symmetries involved. This paper separates result from application, focusing on and clarifying the nature of underlying symmetries. The result is a general set-theoretic version of NFL which speaks to symmetries when arbitrary domains and co-domains are involved. Although our framework is deterministic, we note situations where our deterministic set-theoretic results speak nevertheless to stochastic algorithms.
Solving the Multiple Competitive Facilities Location and Design Problem on the Plane
Authors: Redondo Juana López , Fernández José , García Inmaculada , Ortigosa Pilar M.
Published: February 2009

A continuous location problem in which a firm wants to set up two or more new facilities in a competitive environment is considered. Other facilities offering the same product or service already exist in the area. Both the locations and the qualities of the new facilities are to be found so as to maximize the profit obtained by the firm. This is a global optimization problem, with many local optima. In this paper we analyze several approaches to solve it, namely, three multistart local search heuristics, a multistart simulated annealing algorithm, and two variants of an evolutionary algorithm. Through a comprehensive computational study it is shown that the evolutionary algorithms are the heuristics that provide the best solutions. Furthermore, using a set of problems for which the optimal solutions are known, only the evolutionary algorithms were able to find the optimal solutions for all the instances. The evolutionary strategies presented in this paper can be easily adapted to handle other continuous location problems.
Analyses of Simple Hybrid Algorithms for the Vertex Cover Problem
Authors: Friedrich Tobias , He Jun , Hebbinghaus Nils , Neumann Frank , Witt Carsten
Published: February 2009

Hybrid methods are very popular for solving problems from combinatorial optimization. In contrast, the theoretical understanding of the interplay of different optimization methods is rare. In this paper, we make a first step into the rigorous analysis of such combinations for combinatorial optimization problems. The subject of our analyses is the vertex cover problem for which several approximation algorithms have been proposed. We point out specific instances where solutions can (or cannot) be improved by the search process of a simple evolutionary algorithm in expected polynomial time.
Constraint Handling Using Tournament Selection: Abductive Inference in Partly Deterministic Bayesian Networks
Authors: Galán Severino F. , Mengshoel Ole J.
Published: February 2009

Constraints occur in many application areas of interest to evolutionary computation. The area considered here is Bayesian networks (BNs), which is a probability-based method for representing and reasoning with uncertain knowledge. This work deals with constraints in BNs and investigates how tournament selection can be adapted to better process such constraints in the context of abductive inference. Abductive inference in BNs consists of finding the most probable explanation given some evidence. Since exact abductive inference is NP-hard, several approximate approaches to this inference task have been developed. One of them applies evolutionary techniques in order to find optimal or close-to-optimal explanations. A problem with the traditional evolutionary approach is this: As the number of constraints determined by the zeros in the conditional probability tables grows, performance deteriorates because the number of explanations whose probability is greater than zero decreases. To minimize this problem, this paper presents and analyzes a new evolutionary approach to abductive inference in BNs. By considering abductive inference as a constraint optimization problem, the novel approach improves performance dramatically when a BN's conditional probability tables contain a significant number of zeros. Experimental results are presented comparing the performances of the traditional evolutionary approach and the approach introduced in this work. The results show that the new approach significantly outperforms the traditional one.
A Generic Multi-dimensional Feature Extraction Method Using Multiobjective Genetic Programming
Authors: Zhang Yang , Rockett Peter I.
Published: February 2009

In this paper, we present a generic feature extraction method for pattern classification using multiobjective genetic programming. This not only evolves the (near-)optimal set of mappings from a pattern space to a multi-dimensional decision space, but also simultaneously optimizes the dimensionality of that decision space. The presented framework evolves vector-to-vector feature extractors that maximize class separability. We demonstrate the efficacy of our approach by making statistically-founded comparisons with a wide variety of established classifier paradigms over a range of datasets and find that for most of the pairwise comparisons, our evolutionary method delivers statistically smaller misclassification errors. At very worst, our method displays no statistical difference in a few pairwise comparisons with established classifier/dataset combinations; crucially, none of the misclassification results produced by our method is worse than any comparator classifier. Although principally focused on feature extraction, feature selection is also performed as an implicit side effect; we show that both feature extraction and selection are important to the success of our technique. The presented method has the practical consequence of obviating the need to exhaustively evaluate a large family of conventional classifiers when faced with a new pattern recognition problem in order to attain a good classification accuracy.
The Politics of Exchange Rate—Based Stabilization Versus Structural Reforms in Latin America
Authors: Thies Cameron G. , Arce Moises
Published: February 2009

In the 1990s, the choice of an appropriate exchange rate regime began to capture the attention of policy makers across Latin America. Several countries pegged their currency to the U.S. dollar or even officially substituted the dollar for their national currency. Although economists and political scientists have made piecemeal contributions to the understanding of such policy choices, the literature currently lacks an integrated theoretical framework and a comprehensive test of alternative hypotheses. This study seeks to rectify these gaps in the literature by arguing that policy makers see the implementation of fixed exchange rate regimes as a politically expedient commitment device that allows them to avoid adopting more difficult long-term adjustment policies designed to attain macroeconomic stability and sustainable growth. This hypothesis is tested with alternative hypotheses put forward in the burgeoning literature on exchange rate regime choice. Theoretical expectations are supported by the results of several logit models, which confirm some previous findings in the literature.
Diabetes Self-management in a Latino Social Environment
Authors: Weiler Dawn M. , Crist Janice D.
Published: February 2009

Purpose The purpose of this qualitative descriptive study was to explore the sociocultural influences and social context associated with living with type 2 diabetes among migrant Latino adults.

Methods A qualitative descriptive study using grounded theory techniques was conducted. In-depth semistructured interviews were completed with 10 participants (6 female and 4 male) ranging in age from 46 to 65 years and with a duration of diabetes diagnosis ranging from 1.5 to 40 years.

Results An overarching meta-theme of self-management in a social environment emerged. Every aspect of the process of self-management, as described in the 4 major themes—(1) family cohesion, (2) social stigma of disease, (3) social expectations/perception of “illness,” and (4) disease knowledge and understanding—was influenced by the social context.

Conclusions The familist traditions, central to the Mexican culture, had both positive and negative consequences on diabetes management. Tailoring clinical care and developing novel education approaches, to include family and community, is central to improving the health of this population. Recognizing and acknowledging the social stigma associated with diabetes, for this population, will promote understanding and improve clinician-patient communication. The sociocultural influences that affect diabetes management practices (eg, include family, in particular the primary female caregiver, and establish community- and home-based education sessions) must be integrated into clinical practice. Future research focused on population-defined health and disease self-management, novel educational interventions, and family and community interventions focusing on the concept of social stigma of disease is indicated to further affect the health disparities of this population.
Further neurochemical and behavioural investigation of Brattleboro rats as a putative model of schizophrenia
Authors: Cilia J. , Gartlon JE , Shilliam C. , Dawson LA , Moore SH , Jones DNC
Published: February 2009

Brattleboro (BRAT) rats are a mutant variant of the Long-Evans (LE) strain deficient in the neurohormone vasopressin. BRAT rats show behavioural alterations relevant to schizophrenia. In particular, BRAT rats show deficits in prepulse inhibition (PPI) and alterations in various measures of cognition. The aim of this study was to replicate the reported PPI deficits in BRAT rats and its reversal by antipsychotic drugs and to investigate other behavioural and neurochemical characteristics. Acoustic startle reactivity, PPI, spontaneous and amphetamine-induced locomotor activity (LMA) and ex-vivo steady state neurochemistry were measured in male homozygous BRAT rats and LE rats. The effects of antipsychotics on PPI deficits were also determined. Relative to LE, BRAT rats showed enhanced startle reactivity, hyperactivity to a novel environment, PPI deficits and decreased levels of dopamine and DOPAC (dihydroxyphenylacetic acid) in the frontal cortex. BRAT and LE rats showed similar levels of hyperactivity following amphetamine (0.26 mg/kg s.c.). PPI deficits were attenuated by acute clozapine (5—10 mg/kg s.c.), risperidone (0.1—1 mg/kg i.p.), haloperidol (0.1—0.5 mg/kg p.o.) and less robustly by olanzapine (0.3—3 mg/kg s.c.). Chronic administration of clozapine (5 mg/kg s.c., once daily) attenuated baseline hyperactivity and elevated PPI of both strains. Clozapine concentrations were higher in BRAT brains compared with LE rats. These data confirm the reported PPI deficit in BRAT rats and its reversal by antipsychotic drugs, suggesting BRAT rats may represent a potential model for identifying novel antipsychotic drugs.
Breakdance Injuries and Overuse Syndromes in Amateurs and Professionals
Authors: Kauther Max Daniel , Wedemeyer Christian , Wegner Alexander , Kauther Kai Michael , von Knoch Marius
Published: February 2009

Background

Serious injuries due to breakdancing have been presented only as singular case reports to date. So far, there have been no comprehensive studies about injuries in this sport.

Hypothesis

Professional breakdancing might lead to a higher incidence of injuries than amateur training. Wearing safety equipment is correlated with a decreased incidence of injuries and pain.

Study Design

Descriptive epidemiology study.

Methods

The retrospective study surveyed 40 breakdance professionals and 104 amateurs by questionnaire.

Results

There were 1665 injuries and 206 overuse syndromes found in 380 588 hours of training, leading to a loss of 10 970.6 training days. Professionals reported significantly ( P < .001) more injuries and overuse syndromes with significantly more injuries of the wrist ( P < .001), knee ( P < .001), hip/thigh ( P = .003), ankle/foot ( P = .013), and elbow ( P = .033). No significant differences were found in the time lost per injury and the time lost per overuse syndrome. Pain occurred most frequently in the region of the wrist, spine, shoulder, and ankle. A negative correlation between protective gear and injuries or frequency of pain could not be shown.

Conclusion

Breakdancing must be considered as a potentially high-risk dancing sport. Even with severe injuries, dancers interrupt training only for limited periods of time.

Clinical Relevance

Breakdance injuries and overuse should not be underestimated. Physicians should be aware of the common risks in this highly acrobatic kind of dancing.