bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of HER3 Is a Marker of Dynamic Cell Signaling in Ovarian Cancer: Implications for Pertuzumab Sensitivity
Authors: Nagumo Yoko , Faratian Dana , Mullen Peter , Harrison David J. , Hasmann Max , Langdon Simon P.
Published: September 2009

This study was designed to evaluate the expression of HER receptors as a marker of sensitivity to the humanized anti-HER2 monoclonal antibody pertuzumab in ovarian cancer cells. In a recent clinical trial, low levels of HER3 mRNA have been shown to associate with pertuzumab response when combined with gemcitabine. We sought to define how pertuzumab modulated HER expression levels in ovarian cancer using cell line models to better understand differential and dynamic receptor expression in therapeutic response. Changes in HER3 mRNA expression were also assessed in pertuzumab-treated xenografts. HER3 mRNA and, to a lesser extent, HER2, were down-regulated after stimulation both with heregulin-β1 and epidermal growth factor in a range of ovarian cancer cell lines either growth sensitive or growth resistant to pertuzumab. Pertuzumab reversed this down-regulation and the magnitude of the reversal correlated with pertuzumab sensitivity. The change in HER3 mRNA expression correlated inversely to how much the extracellular signal-regulated kinase and phosphoinositide 3-kinase pathways were dynamically activated with stimulation. Finally, up-regulation of HER3 mRNA was found in cancer xenografts treated with pertuzumab. We conclude that HER3 mRNA is down-regulated by both heregulin-β1 and epidermal growth factor activation. This suggests that in some tumors, low HER3 mRNA expression is driven by, or dependent on, growth factor. HER3 mRNA expression is effectively reversed in pertuzumab-sensitive tumors. These data are consistent with low HER3 mRNA identifying a pertuzumab-sensitive phenotype. (Mol Cancer Res 2009;7(9):1563–71)
The Aberrant Localization of Oncogenic Kit Tyrosine Kinase Receptor Mutants Is Reversed on Specific Inhibitory Treatment
Authors: Bougherara Houcine , Subra Frédéric , Crépin Ronan , Tauc Patrick , Auclair Christian , Poul Marie-Alix
Published: September 2009

Kit is a cell surface type III tyrosine kinase (TK) receptor implicated in cell transformation through overexpression or oncogenic mutation. Two categories of Kit mutants displaying mutations either in the juxtamembrane intracellular domain (regulatory mutants) or in the catalytic domain (catalytic mutants) have been described. To explore the effect of Kit oncogenic mutations on its subcellular localization, we constructed enhanced green fluorescent protein (EGFP)–tagged human Kit chimeras harboring mutations either in the regulatory (V560G) or in the catalytic (D816V) domain. When expressed in Chinese hamster ovary cells, EGFP-tagged wild-type Kit was activated on stem cell factor stimulation, whereas both EGFP-tagged Kit mutants displayed a constitutive TK activity. Constitutively activated mutants exhibited a high-mannose–type N-glycosylation pattern and an intracellular localization, suggesting that these mutants induce downstream oncogenic signaling without the need to reach the cell surface. Inhibition of constitutive Kit TK activity with dasatinib induced a complex, mature N-glycosylation pattern identical to unstimulated wild-type Kit and resulted in the redistribution of the mutants to the plasma membrane. This relocalization was clearly correlated to the inhibition of TK activity because imatinib, a specific inhibitor of the V560G mutant, inactive on the catalytic D816V mutant, induced only the relocalization of the V560G mutant. These data show that on TK inhibition, the aberrant localization of Kit mutants can be fully reversed. Kit mutants are then exported and/or stabilized at the cell surface as inactive and fully N-glycosylated isoforms. (Mol Cancer Res 2009;7(9):1525–33)
Concordant DNA Methylation in Synchronous Colorectal Carcinomas
Authors: Konishi Kazuo , Shen Lanlan , Jelinek Jaroslav , Watanabe Yoshiyuki , Ahmed Saira , Kaneko Kazuhiro , Kogo Mari , Takano Toshihumi , Imawari Michio , Hamilton Stanley R. , Issa Jean-Pierre J.
Published: September 2009

Epigenetic changes have been proposed as mediators of the field defect in colorectal carcinogenesis, which has implications for risk assessment and cancer prevention. As a test of this hypothesis, we evaluated the methylation status of eight genes (MINT1, 2, 31, MLH1, p16, p14, MGMT, and ESR1), as well as BRAF and KRAS mutations, in 57 multiple colorectal neoplasias (M-CRN) and compared these to 69 solitary colorectal cancers (S-CRC). There were no significant differences in methylation between M-CRNs and S-CRCs except for p14 and MGMT that was significantly higher in M-CRNs than S-CRCs (16.1% versus 9.3%; 26.5% versus 17.3%, respectively; P < 0.05). We found significant (P < 0.05) correlations for MINT1 (r = 0.8), p16 (r = 0.8), MLH1 (r = 0.9), and MGMT (r = 0.6) methylation between tumors pairs of the same site (proximal/proximal and distal/distal). KRAS showed no concordance in mutations. BRAF mutation showed concordance in proximal site pairs but was discordant in different site pairs. Histologically, eight of 10 paired cancers with similar locations were concordant for a cribriform glandular configuration. We conclude that synchronous colorectal tumors of the same site are highly concordant for methylation of multiple genes, BRAF mutations, and a cribriform glandular configuration, all consistent with a patient-specific predisposition to particular subtypes of colorectal cancers. Screening for and secondary prevention of colon cancer should take this fact into account.
The Chemopreventive Bioflavonoid Apigenin Inhibits Prostate Cancer Cell Motility through the Focal Adhesion Kinase/Src Signaling Mechanism
Authors: Franzen Carrie A. , Amargo Evangeline , Todorović Viktor , Desai Bhushan V. , Huda Sabil , Mirzoeva Salida , Chiu Karen , Grzybowski Bartosz A. , Chew Teng-Leong , Green Kathleen J. , Pelling Jill C.
Published: September 2009

Prostate cancer mortality is primarily attributed to metastatic rather than primary, organ-confined disease. Acquiring a motile and invasive phenotype is an important step in development of tumors and ultimately metastasis. This step involves remodeling of the extracellular matrix and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling. Epidemiologic studies suggest that the metastatic behavior of prostate cancer may be an ideal target for chemoprevention. The natural flavone apigenin is known to have chemopreventive properties against many cancers, including prostate cancer. Here, we study the effect of apigenin on motility, invasion, and its mechanism of action in metastatic prostate carcinoma cells (PC3-M). We found that apigenin inhibits PC3-M cell motility in a scratch-wound assay. Live cell imaging studies show that apigenin diminishes the speed and affects directionality of cell motion. Alterations in the cytoskeleton are consistent with impaired cell movement in apigenin-treated cells. Apigenin treatment leads to formation of “exaggerated filopodia,” which show accumulation of focal adhesion proteins at their tips. Furthermore, apigenin-treated cells adhere more strongly to the extracellular matrix. Additionally, apigenin decreases activation of FAK and Src, and phosphorylation of Src substrates FAK Y576/577 and Y925. Expression of constitutively active Src blunts the effect of apigenin on cell motility and cytoskeleton remodeling. These results show that apigenin inhibits motility and invasion of prostate carcinoma cells, disrupts actin cytoskeleton organization, and inhibits FAK/Src signaling. These studies provide mechanistic insight into developing novel strategies for inhibiting prostate cancer cell motility and invasiveness.
Matched-Pair Analysis of Race or Ethnicity in Outcomes of Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care
Authors: Chen Leon M. , Li Guojun , Reitzel Lorraine R. , Pytynia Kristen B. , Zafereo Mark E. , Wei Qingyi , Sturgis Erich M.
Published: September 2009

It is unknown whether population-level racial or ethnic disparities in mortality from squamous cell carcinoma of the head and neck (SCCHN) also occur in the setting of standardized multidisciplinary-team directed care. Therefore, we conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a difference in survival exists for African American or Hispanic American compared with non-Hispanic white American SCCHN patients receiving similar care. Matched pairs were 81 African American case and 81 non-Hispanic white control patients and 100 Hispanic American cases and 100 matched non-Hispanic white controls selected from 1,833 patients of a prospective epidemiologic study of incident SCCHN within a single, large multidisciplinary cancer center. Matching variables included age (±10 years), sex, smoking status (never versus ever), site, tumor stage (T1-2 versus T3-4), nodal status (negative versus positive), and treatment. Cases and controls were not significantly different in proportions of comorbidity score, alcohol use, subsite distribution, overall stage, or tumor grade. Matched-pair and log-rank analyses showed no significant differences between cases and controls in recurrence-free, disease-specific, or overall survival. Site-specific analyses suggested that more aggressive oropharyngeal cancers occurred more frequently in minority than in non-Hispanic white patients. We conclude that minority and non-Hispanic white SCCHN patients receiving similar multidisciplinary-team directed care at a tertiary cancer center have similar survival results overall. These results encourage reducing health disparities in SCCHN through public-health efforts to improve access to multidisciplinary oncologic care (and to preventive measures) and through individual clinician efforts to make the best multidisciplinary cancer treatment choices available for their minority patients. The subgroup finding suggests a biologically based racial/ethnic disparity among oropharyngeal patients and that prevention and treatment strategies should be tailored to different populations of these patients.
The Monkey, the Hen, and the Mouse: Models to Advance Ovarian Cancer Chemoprevention
Authors: Lu Karen H. , Yates Melinda S. , Mok Samuel C.
Published: September 2009

This perspective on Romero et al. (beginning on p. 792 in this issue of the journal) discusses the available animal models of ovarian cancer, including the laying hen, non-human primate, and transgenic rodent models, and their relevance to ovarian cancer chemoprevention studies.
School-Based Intervention for the Treatment of Tsunami-Related Distress in Children: A Quasi-Randomized Controlled Trial
Authors: Berger R. , Gelkopf M.
Published: September 2009

Background: On December 26, 2004, a tsunami hit the southern coast of Sri Lanka, leaving thousands dead and injured. Previous research has found significant mental health problems among children exposed to major disasters. School-based universal interventions have shown promise in alleviating distress and posttraumatic symptomatology in children and adolescents. This study evaluated the efficacy of a school-based intervention in reducing stress-related symptomatology among Sri Lankan children exposed to the tsunami. Methods: In a quasi-randomized controlled trial 166 elementary school students (ages 9–15) with significant levels of tsunami exposure and previous traumatic background were randomly assigned to a 12-session structured program ‘ERASE Stress Sri Lanka’ (ES-SL) or to a waiting list (WL) religious class control group. Students were assessed 1 week prior and 3 months after the intervention on measures of posttraumatic symptomatology [including posttraumatic stress disorder (PTSD) and severity of posttraumatic symptomatology], depression, functional problems, somatic problems and hope. Results: This study shows a significant reduction on all outcome variables. PTSD severity, functional problems, somatic complaints, depression and hope scores were all significantly improved in the ES-SL group compared to the WL group. No new cases of PTSD were observed in the experimental group. Conclusion: This study adds to the growing body of evidence suggesting the efficacy of school-based universal approaches in helping children in regions touched by war, terror and disaster and suggests the need to adopt a two-stage approach toward dealing with trauma-exposed students, namely, starting with a universal intervention followed by targeted specialized interventions for those still suffering from posttraumatic distress.
Gender Differences in the Mortality and Outcome of Stroke Patients in Korea
Authors: Oh Mi-Sun , Yu Kyung-Ho , Roh Jae-Kyu , Lee Byung-Chul
Published: September 2009

Background: We aimed to determine gender differences in outcomes and mortality in Korean stroke patients. Methods: We analyzed the demographics, risk factors, in-hospital mortality, functional outcomes at discharge, and any-cause mortality over a 5-year period for 18,364 Korean patients, and determined a cumulative mortality rate using Kaplan-Meier and Cox proportional hazards regression analyses to elucidate gender differences in stroke outcomes. Results: Women suffered strokes that were severer than those suffered by men. Although women had a lower risk of any-cause death than men, they exhibited poorer functional status at discharge. Conclusion: In Korea, women lived longer, but had greater disabilities after strokes than men, indicating the need to develop gender-specific interventions to improve stroke outcomes and reduce the disability burden in women.
Habitual Physical Activity Reduces the Risk of Ischemic Stroke: A Case-Control Study in Southern China
Authors: Liang Wenbin , Lee Andy H. , Binns Colin W. , Zhou Qingkun , Huang Rongsheng , Hu Delong
Published: September 2009

Background: To ascertain the relationship between habitual physical activity and the risk of ischemic stroke among the Chinese population. Methods: A case-control study was conducted in Foshan, Guangdong Province, during 2007–2008. Information on physical activity exposure and lifestyle characteristics was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls (mean age 66 years) using a validated and reliable questionnaire. Logistic regression analyses were performed to assess the association between physical activity levels and the ischemic stroke risk. Results: The control subjects reported significantly longer duration of strenuous sports and moderate activity in recent daily life than the stroke patients. Increased engagements in such leisure time activities were associated with reduced risks of ischemic stroke after adjustment for confounding factors. A significant inverse dose-response relationship was also found for total physical activity exposure, with an adjusted odds ratio of 0.25 (95% confidence interval = 0.14–0.45) for older adults engaged in 22 or more metabolic equivalent task hours per week relative to those engaged in less than 10 metabolic equivalent task hours per week. Conclusions: The study provided evidence of an inverse association between habitual physical activity and the risk of ischemic stroke, which is important for the promotion and encouragement of leisure time exercise activities among elderly Chinese adults.
Pharmacogenetic Testing for Guiding de novo Phenprocoumon Therapy in Stroke Patients
Authors: Arnold Marie-Luise , Grond-Ginsbach Caspar , Kloss Manja , Di Mascio Maria-Teresa , Veltkamp Roland , Ringleb Peter , Lichy Christoph
Published: September 2009

Background: For many conditions causing transient ischemic attack or minor stroke, secondary prevention with early initiation of oral anticoagulation is indicated. The individual response to coumarins is known to vary widely and is not well predicted by clinical variables. Patients’ discharge from hospital care is often delayed only because the therapeutic target range has not been reached yet. A feasible tool to guide coumarin dosing and thereby safely shortening time in hospital is required. Methods: We established a polymerase chain reaction technique for rapid genotyping of the vitamin K epoxide reductase complex (VKORC1), which is the pharmaceutical target of the coumarins. C283 + 837C –> T (rs2359612) genotypes were determined in 49 patients who underwent de novo oral anticoagulation with phenprocoumon for cerebrovascular disease. Other variables potentially affecting phenprocoumon sensitivity were systematically evaluated. Results: Of 49 genotyped patients, 47 were treated in hospital until an international normalized ratio (INR) of 2–3 was reached. The time and the cumulative dose of phenprocoumon necessary to achieve the target INR both were strongly dependent on the individual C283 + 837C –> T genotype (Kruskal-Wallis test p = 0.0002, and p < 0.0001, respectively). Carriers of the TT genotype reached an INR of 2–3 after a mean time of 3.2 days (n = 5), CT carriers after 4.4 days (n = 27), and CC carriers after 6.5 days (n = 15). No other variable, including body weight, was significantly correlated with the treatment response. Conclusion: In patients with cerebrovascular disease, genotyping for VKORC1 alone can strongly predict the individual response to de novo phenprocoumon treatment. The size of the pharmacogenetic test’s potential effect on a more efficient use of hospital capacities remains to be shown by a controlled interventional study.
Recent Causes of Subconjunctival Hemorrhage
Authors: Mimura Tatsuya , Usui Tomohiko , Yamagami Satoru , Funatsu Hideharu , Noma Hidetaka , Honda Norihiko , Amano Shiro
Published: September 2009

Purpose: To assess the relationship between the incidence of subconjunctival hemorrhage (SCH) and age during each season of the year, and to examine recent risk factors for SCH. Methods: A total of 161 patients with SCH aged 1–94 years were involved in the study. The age, gender, medical history and ocular history were determined for all subjects. Results: The peak age of onset of SCH was between 61 and 70 years. Fourteen patients (77.7%) had trauma or contact-lens-induced injury, and 4 patients (22.3%) among the younger patients aged 0–40 years had an unknown etiology. Among the older patients aged 61–94 years, the chief risk factor for SCH was hypertension (47.5%), followed by unknown etiology (39.4%) and then diabetes (13.1%). Conclusion: These results suggest that the major current risk factors for SCH are trauma and contact-lens-induced injury in younger patients, while hypertension is the main factor in older patients. The incidence of acute hemorrhagic conjunctivitis was decreased.
Stimulus Parameters for Goldmann Kinetic Perimetry in Nonorganic Visual Loss
Authors: Ebneter Andreas , Pellanda Niccolo , Kunz Andrea , Mojon Stefania , Mojon Daniel S.
Published: September 2009

Objective: To investigate the influence of the stimulus parameters on perimetry at various distances and draw conclusions for the clinical exploration of nonorganic visual loss. Methods: Visual field testing using Goldmann kinetic perimetry was performed on 15 healthy volunteers. The I/1e isopter at 33 cm was compared to the I/1e, II/1e and I/2e isopters at 66 cm. The 0/1e isopter at 33 cm was compared to the 0/1e, I/1e and 0/2e isopters at 66 cm. Results: Doubling the examination distance without adjusting the stimulus parameters resulted in significant perimetric visual field constriction. Doubling the stimulus diameter resulted in perimetric visual field expansion by a factor of 2.26 and 3.32 for I/1e and 0/1e, respectively. Increasing stimulus luminance by a factor of 3.17 caused expansion by a factor of 2.15 and 2.32 for I/1e and 0/1e, respectively. Conclusions: To avoid falsely diagnosing visual field constriction, stimulus parameters need to be adjusted when visual field testing is performed at double distance. Increasing stimulus luminance was more appropriate than augmenting stimulus size.
Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor
Authors: Itoh Naohiro , Okochi Masayasu , Tagami Shinji , Nishitomi Kouhei , Nakayama Taisuke , Yanagida Kanta , Fukumori Akio , Jiang Jingwei , Mori Kohji , Hosono Motoko , Kikuchi Jyunko , Nakano Yuko , Takinami Yoshihiko , Dohi Keiji , Nishigaki Atsuko , Takemoto Hiroshi , Minagawa Kazuyuki , Katoh Takaaki , Willem Michael , Haass Christian , Morihara Takashi , Tanaka Toshihisa , Kudo Takashi , Hasegawa Hiroshi , Nishimura Masaki , Sakaguchi Gaku , Kato Akira , Takeda Masatoshi
Published: September 2009

Alzheimer-disease-associated β-amyloid (Aβ) is produced by sequential endoproteolysis of β-amyloid protein precursor (βAPP): the extracellular portion is shed by cleavage in the juxtamembrane region by β-amyloid-cleaving enzyme (BACE)/β-secretase, after which it is cleaved by presenilin (PS)/γ-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces Aβ generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce Aβ production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces Aβ generation without affecting BACE or PS/γ-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and βAPP, which reduces β-cleavage of βAPP. Therefore, the data demonstrate that Dx-E represents a novel Aβ-reducing process which could have fewer side effects than secretase inhibitors.
Incremental Prognostic Value of Myocardial Perfusion Imaging in Patients Referred to Stress Single-Photon Emission Computed Tomography With Renal Dysfunction
Authors: Al-Mallah Mouaz H. , Hachamovitch Rory , Dorbala Sharmila , Di Carli Marcelo F.
Published: September 2009

Background—

Coronary artery disease is the main cause of mortality and morbidity in patients with impaired renal function. The aim of this study was to evaluate the prognostic implications of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with impaired renal function.

Methods and Results—

We included 7348 consecutive patients (mean age, 64�13 years; 51% men) referred for SPECT-MPI between March 2002 and October 2006. Renal function was estimated using the estimated glomerular filtration rate formula. Patients were followed up for the incidence of all-cause mortality. Patients with decreased glomerular filtration rate were more often older, with higher prevalence of conventional risk factors (
P
<0.001). After a median follow-up of 2.6 years (25th to 75th percentiles, 1.5 to 3.7), 693 (9.4%) patients died. The risk of death increased with worsening kidney function. At each stage of impaired renal function, patients with abnormal SPECT-MPI had increased hazard of adverse events (
P
<0.0001). Using Cox proportional hazards analysis, the magnitude of total perfusion deficit and ischemia on MPI were associated with worse outcome after adjusting for confounding variables including glomerular filtration rate and ejection fraction.

Conclusions—

SPECT-MPI adds modest incremental prognostic information to identify patients at higher relative risk of death across a wide spectrum of renal function.
Baseline Values but Not Treatment-Induced Changes in Carotid Intima-Media Thickness Predict Incident Cardiovascular Events in Treated Hypertensive Patients
Authors: Zanchetti Alberto , Hennig Michael , Hollweck Regina , Bond Gene , Tang Rong , Cuspidi Cesare , Parati Gianfranco , Facchetti Rita , Mancia Giuseppe
Published: September 2009

Background—

Baseline carotid intima-media thickness (IMT) and plaques are considered predictors of cardiovascular events, but whether they maintain predictive value in treated hypertensive patients and whether time-related (or treatment-induced) IMT changes are additional predictors are unknown.

Methods and Results—

Analyses were performed of the data from the European Lacidipine Study on Atherosclerosis (ELSA), a large, randomized, intervention trial in which 2334 hypertensive patients from 7 European countries were followed up under effective antihypertensive treatment for 3.75 years. Kaplan–Meier curves indicated progressively lower survival free of any type of outcome except stroke, with increasing baseline IMT quartiles or increasing IMT values, even after adjustment for major baseline risk factors. Incidence of any outcome except stroke also was related to baseline number of carotid plaques. However, when both baseline and on-treatment IMT values were entered in Cox proportional-hazards models, differences in IMT compared with baseline did not predict cardiovascular outcomes. Although on-treatment rather than baseline IMT values significantly entered some of the proportional-hazards models, baseline and on-treatment IMTs were highly correlated, and therefore these results are inconclusive.

Conclusions—

ELSA shows that carotid intima-media thickening and plaques are important added risks of cardiovascular outcomes in a treated hypertensive population independently of blood pressure and traditional risk factors. However, the analysis failed to show a predictive role of treatment-dependent IMT changes. These negative conclusions should be tempered by the limitations inherent in the smallness of these changes compared with the large individual differences in baseline IMTs.
Novel Small Interfering RNA–Containing Solution Protecting Donor Organs in Heart Transplantation
Authors: Zheng Xiufen , Lian Dameng , Wong Arthur , Bygrave Michael , Ichim Thomas E. , Khoshniat Mahdieh , Zhang Xusheng , Sun Hongtao , De Zordo Tobias , Lacefield James C. , Garcia Bertha , Jevnikar Anthony M. , Min Wei-Ping
Published: September 2009

Background—

Ischemia/reperfusion injury is a major factor in graft quality and subsequent function in the transplantation setting. We hypothesize that the process of RNA interference may be used to “engineer” a graft to suppress expression of genes associated with inflammation, apoptosis, and complement, which are believed to cause ischemia/reperfusion injury. Such manipulation of pathological gene expression may be performed by treatment of the graft ex vivo with small interfering RNA (siRNA) as part of the preservation procedure.

Methods and Results—

Heart grafts from BALB/c mice were preserved in UW solution (control) or UW solution containing siRNAs targeting tumor necrosis factor-α, C3, and Fas genes (siRNA solution) at 4°C for 48 hours and subsequently transplanted into syngeneic recipients. Tumor necrosis factor-α, C3, and Fas genes were elevated by ischemia/reperfusion injury after 48 hours of preservation in UW solution. Preservation in siRNA solution knocked down gene expression at the level of messenger RNA and protein in the grafts after transplantation. All grafts preserved in siRNA solution showed strong contraction, whereas grafts preserved in control solution demonstrated no detectable contraction by high-frequency ultrasound scanning. siRNA solution–treated organs exhibited improved histology and diminished neutrophil and lymphocyte infiltration compared with control solution–treated organs. Furthermore, the treated heart grafts retained strong beating up to the end of the observation period (>100 days), whereas all control grafts lost function within 8 days.

Conclusion—

Incorporation of siRNA into organ storage solution is a feasible and effective method of attenuating ischemia/reperfusion injury, protecting cardiac function, and prolonging graft survival.
A Prospective Study of Bone Lead Concentration and Death From All Causes, Cardiovascular Diseases, and Cancer in the Department of Veterans Affairs Normative Aging Study
Authors: Weisskopf Marc G. , Jain Nitin , Nie Huiling , Sparrow David , Vokonas Pantel , Schwartz Joel , Hu Howard
Published: September 2009

Background—

Blood lead concentration has been associated with mortality from different causes in several studies. Many effects of lead exposure that might increase risk of death are likely to result from cumulative exposure, for which bone lead is a better biomarker than blood lead. The association between bone lead levels and mortality has not been explored.

Methods and Results—

We prospectively assessed the association between both blood lead and bone lead, analyzed with the use of K-shell x-ray fluorescence, and mortality among 868 men in the Normative Aging Study. We identified 241 deaths over an average of 8.9 (SD=3.9) years of follow-up. We calculated adjusted hazard ratios and 95% confidence intervals using Cox proportional hazards. Compared with the lowest tertile of patella bone lead, the fully adjusted hazard ratios in the highest tertile for all-cause, cardiovascular (n=137 deaths), and ischemic heart disease (n=62 deaths) mortality were 1.25 (95% confidence interval, 0.82 to 1.92), 1.42 (95% confidence interval, 0.80 to 2.51), and 1.87 (95% confidence interval, 0.77 to 4.53), respectively. Results were similar for tibia lead. Bone lead was not associated with cancer, and blood lead was not associated with any mortality category.

Conclusions—

We found bone lead to be associated with a slight increase in all-cause and cardiovascular mortality in an environmentally exposed population with low blood lead levels, but this did not reach statistical significance. This study suggests that cumulative lead exposure from prior decades of high environmental exposures may affect risk of death despite recent declines in environmental lead exposure, but studies with more follow-up are needed.
Pathophysiological Changes in Calf Muscle Predict Mobility Loss at 2-Year Follow-Up in Men and Women With Peripheral Arterial Disease
Authors: McDermott Mary McGrae , Ferrucci Luigi , Guralnik Jack , Tian Lu , Liu Kiang , Hoff Frederick , Liao Yihua , Criqui Michael H.
Published: September 2009

Background—

Associations of pathophysiological calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease are unknown.

Methods and Results—

Three hundred seventy participants with peripheral arterial disease underwent baseline measurement of calf muscle area, density, and percent fat with the use of computed tomography. Participants were followed up annually for 2 years. The outcome of mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down 1 flight of stairs without assistance among those without baseline mobility limitations. Additional outcomes were ≥20% decline in 6-minute walk distance and becoming unable to walk for 6 minutes continuously among participants who walked continuously for 6 minutes at baseline. With adjustment for age, sex, race, body mass index, the ankle-brachial index, smoking, physical activity, relevant medications, and comorbidities, lower calf muscle density (
P
for trend <0.001) and lower calf muscle area (
P
for trend=0.039) were each associated with increased mobility loss rates. Compared with participants in the highest baseline tertiles, participants in the lowest tertile of calf muscle percent fat had a hazard ratio of 0.18 for incident mobility loss (95% confidence interval, 0.06 to 0.55;
P
=0.003), and participants in the lowest tertile of muscle density had a 3.50 hazard ratio for incident mobility loss (95% confidence interval, 1.28 to 9.57;
P
=0.015). No significant associations of calf muscle characteristics with 6-minute walk outcomes were observed.

Conclusions—

Our findings suggest that interventions to prevent mobility loss in peripheral arterial disease should focus on reversing pathophysiological findings in calf muscle.
A Property Rights Approach to Externality Problems: Planning Based on Compensation Rules
Authors: van der Krabben Erwin
Published: September 2009

Most European countries have implemented some kind of land use planning based on exclusionary zoning principles to achieve spatial goals. This paper argues that, to reduce externality problems, regulatory planning is not always the best planning solution. Therefore, an alternative planning approach, which makes use of compensation rules, is suggested in this paper. This compensatory planning approach is based on property rights theory and refers to recent applications of this theory to planning practice. To illustrate the usefulness of such an approach, it is applied to the planning of out-of-town retail development in The Netherlands. The paper aims to demonstrate how deficiencies in the property rights regime can be repaired to deal with externality problems, achieving a more socially acceptable outcome of out-of-town retail development. The paper concludes with a discussion of the value of spontaneous order solutions for planning practice, by introducing four pragmatic rules on how to choose between different types of government interventions.
Absence of QTc Prolongation in a Thorough QT Study With Subcutaneous Liraglutide, a Once‐Daily Human GLP‐1 Analog for Treatment of Type 2 Diabetes
Authors: Chatterjee Dhruba J. , Khutoryansky Naum , Zdravkovic Milan , Sprenger Craig R. , Litwin Jeffrey S.
Published: September 2009

The objective of this study was to establish effects of liraglutide on the QTc interval. In this randomized, placebo‐controlled, double‐blind crossover study, 51 healthy participants were administered placebo, 0.6, 1.2, and 1.8 mg liraglutide once daily for 7 days each. Electro cardiograms were recorded periodically over 24 hours at the end of placebo and highest dosing periods. Four different models for QT correction were used: QTci, as the primary endpoint, and QTciL, QTcF, and QTcB as secondary endpoints. The upper bound of the 1‐sided 95% confidence interval for time‐matched, baseline‐corrected, placebo‐subtracted QTc intervals was <10 ms for all 4 correction methods. Moxifloxacin (400 mg) increased QTc intervals by 10.6 to 12.3 ms at 2 hours. There was no concentration‐exposure dependency on QTc interval changes by liraglutide and no QTc thresholds above 500 ms or QTc increases >60 ms. The authors conclude that liraglutide caused no clinically relevant increases in the QTc interval.
Matrix-based sequencing in multiple re-entrant flowlines
Authors: Petrović Tamara , Bogdan Stjepan
Published: September 2009

In this article, we address issues related to modelling of a discrete event system in a way that would effectively provide an easy implementation of the scheduling policy on the actual controller and at the same time would provide an answer on how profound the utilization of the system resources is. Herein we propose a method that relies on usage of a matrix model and a max-plus algebra model. The idea is to use the advantages of each of the given models. A system, initially given in matrix form, can be transferred into a max-plus model under the given sequence. In the case of structural changes, the system matrix model can be easily modified and hence supervisory matrix controller redesign is straightforward. On the other hand, the max-plus model is suitable for performance analysis, which in some cases could be difficult if a matrix model is used. Moreover, max-plus algebra represents the system on the higher level of abstraction, which is suitable for investigation of particular properties of discrete event systems. In addition, using both models, we propose a method for determining a scheduling sequence that is not well formed.
On-board image-based vehicle detection and tracking
Authors: Ponsa Daniel , Serrat Joan , López Antonio M.
Published: September 2009

In this paper we present a computer vision system for daytime vehicle detection and localization, an essential step in the development of several types of advanced driver assistance systems. It has a reduced processing time and high accuracy thanks to the combination of vehicle detection with lane-markings estimation and temporal tracking of both vehicles and lane markings. Concerning vehicle detection, our main contribution is a frame scanning process that inspects images according to the geometry of image formation, and with an Adaboost-based detector that is robust to the variability in the different vehicle types (car, van, truck) and lighting conditions. In addition, we propose a new method to estimate the most likely three-dimensional locations of vehicles on the road ahead. With regards to the lane-markings estimation component, we have two main contributions. First, we employ a different image feature to the other commonly used edges: we use ridges, which are better suited to this problem. Second, we adapt RANSAC, a generic robust estimation method, to fit a parametric model of a pair of lane markings to the image features. We qualitatively assess our vehicle detection system in sequences captured on several road types and under very different lighting conditions. The processed videos are available on a web page associated with this paper. A quantitative evaluation of the system has shown quite accurate results (a low number of false positives and negatives) at a reasonable computation time.
Measurement and modelling of disturbances in a servo track writer and advanced loop shaping to achieve higher track density
Authors: Jingliang Zhang  , Chunling Du  , Shanjiao Jiang
Published: September 2009

In this paper we present the idea of hybrid servo track writing and give a complete description of the developed hybrid servo track writer platform including its main functions and servo mechanism. The major disturbances and noise level in media-level servo track writing are identified based on the position error signal measured on the hybrid servo track writer platform. A dual-stage servo system, which is applicable in servo writing, is proposed and implemented on the experimental platform. With the disturbances and noise models, an advanced loop-shaping scheme based on Kalman—Yakubovic—Popov lemma is used to optimize the controller for the micro-actuator servo loop. The experimental results show that the tracking accuracy can reach 6 nm, which is able to support a track density of more than 400 000 tracks per inch.
Learning to Click
Authors: Williamson Sprague Elaine , Dahl Darren W.
Published: September 2009

The incorporation of personal response system (PRS) clickers into teaching pedagogy has created implications for teaching practice and student satisfaction. Using a current undergraduate business student population, the authors measure student attitudes and preferences and identify student performance outcomes relating to the use of PRS clickers. Study results validate the broad applicability of this technology by showing positive student attitudes, learning experiences, and the mitigation of barriers toward acceptance of this technology. Importantly, measures of student performance correlate to self-reported learning outcomes realized through using PRS clickers. The study also finds evidence that PRS clickers benefit those students who are frequently disadvantaged in the classroom. Specifically, students with a low need for cognition or facing cultural barriers are shown to have a better learning experience when using clicker technology. The article concludes with recommendations on applying PRS clicker technology to teaching practice and identifies areas for future investigation.
The Relationship between Posterior Tibial Slope and Anterior Cruciate Ligament Injuries
Authors: Todd Michael S. , Lalliss Steve , Garcia E'Stephan , DeBerardino Thomas M. , Cameron Kenneth L.
Published: September 2009

Background

Two previous studies have examined the association between an increased posterior tibial slope and anterior cruciate ligament (ACL) injuries as measured on plain radiographs. The study results were contradictory, with 1 reporting a statistical difference and the other showing no association.

Purpose

To determine if there is a difference in posterior tibial slope angle between patients with a history of noncontact ACL injury and a control group with no history of ACL injury. A secondary objective was to examine differences in tibial slope angle between male and female subjects within each group.

Study Design

Case-control study; Level of evidence, 3.

Methods

We identified all noncontact ACL injuries that were treated operatively at the United States Military Academy, West Point, New York, from 2004 to 2007. We digitally measured the posterior tibial slope from plain film radiographs of 140 noncontact ACL injuries, stratified them by sex, and compared them with a control cohort of 179 patients and radiographs.

Results

Subjects in the noncontact ACL group had significantly greater slope angles (9.39° ± 2.58°) than did control subjects (8.50° ± 2.67°) (P = .003). The trend toward greater tibial slope angles in the noncontact ACL group was also observed when each sex was examined independently; however, the difference was only statistically significant for the female subjects between the injury and control groups (9.8° ± 2.6° vs 8.20° ± 2.4°) (P = .002).

Conclusion

Despite the identification of an increased posterior tibial slope as a possible risk factor for women, more research that combines the multifactorial nature of an ACL injury must be performed.
Histologic Findings and Possible Causes of Osteochondritis Dissecans of the Knee
Authors: Uozumi Hiroaki , Sugita Takehiko , Aizawa Toshimi , Takahashi Atsushi , Ohnuma Masahiro , Itoi Eiji
Published: September 2009

Background

The histologic findings of osteochondritis dissecans of the knee vary widely, leading to differences in the interpretation of its origins.

Hypothesis

The differences in the histologic findings of osteochondritis dissecans might represent a course of pathologic progression.

Study Design

Descriptive laboratory study.

Methods

Twelve knees in 11 patients (average age, 16 years) with osteochondritis dissecans of the medial femoral condyle were treated by biological internal fixation. During the surgery, cylinder osteochondral plugs were taken from the center of the osteochondritis dissecans lesion and examined with light microscopy.

Results

A complete or partial cleft separated the specimens into 2 parts: basal and fragment sides. The surface of the basal side was covered with dense fibrous or cartilaginous tissue and active bone remodeling was found beneath the surface. In the fragment side, the deep surface was also covered with dense fibrous or cartilaginous tissue and the articular surface consisted of normal articular cartilage. The area between these 2 surfaces could be classified into 3 types: (1) necrotic subchondral trabeculae, (2) viable subchondral trabeculae, and (3) cartilage without bone trabeculae.

Conclusion

Based on the histologic findings of this study, the following origins and the pathologic progression of osteochondritis dissecans might be assumed: the initial change in the subchondral area is bone necrosis or subchondral fracture; the necrotic bone is then absorbed and replaced either by viable subchondral trabeculae or cartilage without bone trabeculae.

Clinical Relevance

The results of this histologic study provide readers with several insights about the causes and treatment options of osteochondritis dissecans.
Processing and Characterization of Jute-Epoxy Composites Reinforced with SiC Derived from Rice Husk
Authors: Satapathy Alok , Alok Kumar Jha  , Mantry Sisir , Singh S.K. , Patnaik Amar
Published: September 2009

This article depicts the processing and mechanical characterization of a new class of multi-phase composites consisting of epoxy resin reinforced with jute fiber and filled with silicon carbide (SiC) particulates. The SiC used as filler material in this work was prepared from rice husk through plasma-processing technique. The effect of filler in modifying the physical and mechanical properties of jute—epoxy composites has been studied. It is found that the incorporation of rice husk derived SiC modifies the tensile, flexural, and inter-laminar shear strengths of the jute—epoxy composites. The micro-hardness and density of the composites are also greatly influenced by the content of these fillers.
Similarities and Differences in the Transition Expectations of Youth and Parents
Authors: Powers Kristin , Geenen Sarah , Powers Laurie E.
Published: September 2009

This study explored similarities and differences in the transition expectations of parents and youth. Independent samples of parents ( N = 270) of transition-age youth with disabilities and students with disabilities ( N = 242) were surveyed about the importance of achieving various adult goals, having specific types of transition-related training and skills, and potential barriers to transition. Factor analysis of the data yielded six scales, and significant differences were found between youth and parents on four of these scales indicating that parents tend to value teacher support more, whereas youth reported higher levels of self-esteem, greater barriers to transition, and more interest in assuming caretaking roles in their future. Parents and students were in agreement, however, around the goals they felt were most important for transition: finishing high school, having health insurance, and having access to a good doctor.
Synthesis and Characterization of Aromatic Polyimides containing Trifluoromethyl Group from Bis(4-amino-2-trifluoromethylphenyl)ether and Aromatic Tetracarboxylic Dianhydrides
Authors: Satoh Arata , Morikawa Atsushi
Published: September 2009

Aromatic polyimides, which had trifluoromethyl group at 2,2′-position of the diphenyl ether, were synthesized from bis(4-amino-2-trifluoromethylphenyl)ether (1) and previously prepared tetracarboxylic dianhydrides, 3,3′′′,4,4 ′′′- p-quaterphenyltetracarboxylic dianhydride (2d), 3,3′′′ ′,4,4′′′ ′- p-quinquephenyltetracarboxylic dianhydride (2e) and 3,3′ ′ ′ ′ ′ ,4,4 ′ ′ ′ ′ ′ - p-sexiphenyltetracarboxylic dianhydride (2f), and the properties were compared than those of corresponding polyimides from commercially available tetracarboxylic dianhydrides. The polyimides were synthesized by the conventional two-step procedure of ring-opening polyaddition in N-methyl-2-pyrrolidinone (NMP) and subsequent thermal cyclic dehydration. The polyimides were characterized by differential scanning calorimetry (DSC), thermogravimetry, and dynamic mechanical analysis (DMA). The polyimides showed excellent thermal stability, and had glass transition temperature ( Tg) at 234—300 °C. The properties of polyimides were compared with those of previously prepared polyimides, which had phenyl group at 2,2′-position of the diphenyl ether, and the effect of the trifluoromethyl groups at the 2, 2′- positions of the diphenyl ether were observed in the thermal properties, solubility and optical properties of polyimides.
New Sulfonated Polyethers and Polynaphthylimides based on TNT Derivatives
Authors: Rusanov Alexander L. , Komarova Ludmila G. , Bulycheva Elena G. , Bugaenko Margarita G. , Belomoina Nataliya M.
Published: September 2009

New sulfonated and non-sulfonated monomers — dinitro and diamino compounds — were prepared on the basis of 1,3,5-trinitrobenzene (TNB) which is the demethylation product of 2,4,6-trinitrotoluene (TNT). The sulfonated dinitrocompounds interacted with different binuclear bis-phenols under the conditions of aromatic nucleophilic nitrodisplacement reactions. Polyethers of moderate molecular weights were prepared on the basis of dinitrocompound containing electron-withdrawing 3,5-dinitrodiphenyl sulfone-4′-sulfonic acid “bridging” groups. Copolymers and blends with other sulfonated polymers were prepared to improve the film-forming properties of the polyethers developed on the basis of 3,5-dinitrodiphenyl sulfone-4′-sulfonic acid. High molecular weight sulfonated polynaphthylimides were prepared by the interaction of sulfonated diamine containing electron-donating ether group — 3,5-diaminodiphenyl ether-4′-sulfonic acid — with bis(naphthalic anhydride)s. The sulfonated polyethers and polynaphthylimides thus obtained contain sulfonic acid groups in the side chains.