bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical ventilation causes airway distension with proinflammatory sequelae in mice
Authors: Nickles Hannah T. , Sumkauskaite Migle , Wang Xin , Wegner Ingmar , Puderbach Michael , Kuebler Wolfgang M.
Published: May 2014

The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies.
Progress in solving the sex hormone paradox in pulmonary hypertension
Authors: Lahm Tim , Tuder Rubin M. , Petrache Irina
Published: May 2014

Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with marked morbidity and mortality. Even though being female represents one of the most powerful risk factors for PAH, multiple questions about the underlying mechanisms remain, and two “estrogen paradoxes” in PAH exist. First, it is puzzling why estrogens have been found to be protective in various animal models of PAH, whereas PAH registries uniformly demonstrate a female susceptibility to the disease. Second, despite the pronounced tendency for the disease to develop in women, female PAH patients exhibit better survival than men. Recent mechanistic studies in classical and in novel animal models of PAH, as well as recent studies in PAH patients, have significantly advanced the field. In particular, it is now accepted that estrogen metabolism and receptor signaling, as well as estrogen interactions with key pathways in PAH development, appear to be potent disease modifiers. A better understanding of these interactions may lead to novel PAH therapies. It is the purpose of this review to 1) review sex hormone synthesis, metabolism, and receptor physiology; 2) assess the context in which sex hormones affect PAH pathogenesis; 3) provide a potential explanation for the observed estrogen paradoxes and gender differences in PAH; and 4) identify knowledge gaps and future research opportunities. Because the majority of published studies investigated 17β-estradiol and/or its metabolites, this review will primarily focus on pulmonary vascular and right ventricular effects of estrogens. Data for other sex hormones will be discussed very briefly.
Strong Convergence on Iterative Methods of Cesàro Means for Nonexpansive Mapping in Banach Space
Authors: Zhu Zhichuan , Chen Rudong
Published: May 2014

Two new iterations with Cesàro's means for nonexpansive mappings are proposed and the strong convergence is obtained asn→∞. Our main results extend and improve the corresponding results of Xu (2004), Song and Chen (2007), and Yao et al. (2009).
Hyaluronan Produced by Smooth Muscle Cells Plays a Critical Role in Neointima Formation
Authors: Vigetti Davide , Deleonibus Sara , Karousou Eugenia , Viola Manuela , De Luca Giancarlo , Passi Alberto
Published: May 2014

Large body of evidence supports the idea that microenvironment plays a critical role in several pathologies including atherosclerosis and cancer. The amount of hyaluronan (HA) is involved in the microenvironment alterations and the concentration of this polymer reflects the progression of the diseases promoting neoangiogenesis, cell migration, and inflammation. The HA synthesis is regulated by several factors: UDP sugar precursors availability and the phosphorylation of synthetic enzyme HAS2 as well as specific drugs reducing the UDP precursors. The HAS2 phosphorylation is done by AMP kinase, a sensor of cell energy. When the cells have low energy, AMP kinase is activated and modifies covalently the regulatory enzymes, blocking all biosynthetic processes and activating the energy producing metabolism. It was recently reported that the hexosamine biosynthetic pathway (HBP) may increase the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. We demonstrated that the increase of HA synthesis depends on the HAS2 post translational modification O-GlcNAcylation, which increases HA secretion modifying a residue different from the phosphorylation site of AMP kinase. In this report we highlighted the critical aspects of the post translational HAS2 regulation and its influence on HA synthesis.
Implementation Study of Patient-Ready Syringes Containing 25 mg/mL Methotrexate Solution for Use in Treating Ectopic Pregnancy
Authors: Respaud R. , Gaudy A. S. , Arlicot C. , Tournamille J. F. , Viaud-Massuard M. C. , Elfakir C. , Antier D.
Published: May 2014

Background.Ectopic pregnancy (EP) is a significant cause of morbidity and mortality during the first trimester of pregnancy. Small unruptured tubal pregnancies can be treated medically with a single dose of methotrexate (MTX).Objective.The aim of this study was to evaluate the stability of a 25 mg/mL solution of MTX to devise a secure delivery circuit for the preparation and use of this medication in the management of EP.Method.MTX solutions were packaged in polypropylene syringes, stored over an 84-day period, and protected from light either at +2 to +8°C or at 23°C. We assessed the physical and chemical stability of the solutions at various time points over the storage period. A pharmaceutical delivery circuit was implemented that involved the batch preparation of MTX syringes.Results.We show that 25 mg/mL MTX solutions remain stable over an 84-day period under the storage conditions tested. Standard doses were prepared, ranging from 50 mg to 100 mg. The results of this study suggest that MTX syringes can be prepared in advance by the pharmacy, ready to be dispensed at any time that a diagnosis of EP is made.Conclusion.The high stability of a 25 mg/mL MTX solution in polypropylene syringes makes it possible to implement a flexible and cost-effective delivery circuit for ready-to-use preparations of this drug, providing 24-hour access and preventing treatment delays.
The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial
Authors: Qasemzadeh Mohammad Javad , Fathi Mahdi , Tashvighi Maryam , Gharehbeglou Mohammad , Yadollah-Damavandi Soheila , Parsa Yekta , Rahimi Ebrahim
Published: May 2014

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children.Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization.Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P<0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P=0.044) and hospitalization (P=0.004).Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID:AEARCTR-0000187.
The Effects of Test Preference, Test Access, and Navigation on Colorectal Cancer Screening
Authors: Daskalakis Constantine , Vernon Sally W. , Sifri Randa , DiCarlo Melissa , Cocroft James , Sendecki Jocelyn Andrel , Myers Ronald E.
Published: May 2014

Background: Little is known about how colorectal cancer screening test preferences operate together with test access and navigation to influence screening adherence in primary care.

Methods: We analyzed data from a randomized trial of 945 primary care patients to assess the independent effects of screening test preference for fecal immunochemical test (FIT) or colonoscopy, mailed access to FIT and colonoscopy, and telephone navigation for FIT and colonoscopy, on screening.

Results: Preference was not associated with overall screening, but individuals who preferred FIT were more likely to complete FIT screening (P = 0.005), whereas those who preferred colonoscopy were more likely to perform colonoscopy screening (P = 0.032). Mailed access to FIT and colonoscopy was associated with increased overall screening (OR = 2.6, P = 0.001), due to a 29-fold increase in FIT use. Telephone navigation was also associated with increased overall screening (OR = 2.1, P = 0.005), mainly due to a 3-fold increase in colonoscopy performance. We estimated that providing access and navigation for both screening tests may substantially increase screening compared with a preference-tailored approach, mainly due to increased performance of nonpreferred tests.

Conclusions: Preference influences the type of screening tests completed. Test access increases FIT and navigation mainly increases colonoscopy. Screening strategies providing access and navigation to both tests may be more effective than preference-tailored approaches.

Impact: Preference tailoring in colorectal cancer screening strategies should be avoided if the objective is to maximize screening rates, although other factors (e.g., costs, necessary follow-up) should also be considered. Cancer Epidemiol Biomarkers Prev; 23(8); 1521–8. ©2014 AACR.
Risk Factors Associated with Rectal Neuroendocrine Tumors: A Cross-Sectional Study
Authors: Jung Yoon Suk , Yun Kyung Eun , Chang Yoosoo , Ryu Seungho , Park Jung Ho , Kim Hong Joo , Cho Yong Kyun , Sohn Chong Il , Jeon Woo Kyu , Kim Byung Ik , Park Dong Il
Published: May 2014

Background: The incidence of rectal neuroendocrine tumors (NET) has been increasing since the implementation of the screening colonoscopy. However, very little is known about risk factors associated with rectal NETs. We examined the prevalence of and the risk factors for rectal NETs in a Korean population.

Methods: A cross-sectional study was performed on 62,171 Koreans who underwent screening colonoscopy. The clinical characteristics and serum biochemical parameters of subjects with rectal NET were compared with those of subjects without rectal NET using multivariate logistic regression.

Results: Of a total of 57,819 participants, 101 [OR, 0.17%; 95% confidence interval (CI), 0.14–0.20] had a rectal NET. Young age (<50 years; OR, 2.09; 95% CI, 1.06–4.15), male gender (OR, 1.92; 95% CI, 1.15–3.20), alcohol drinking [adjusted OR (AOR), 1.56; 95% CI, 1.01–2.42], and a low high-density lipoprotein-cholesterol (HDL-C) level (AOR, 1.85; 95% CI, 1.10–3.11) were independent risk factors for rectal NETs. Cigarette smoking, fatty liver, metabolic syndrome, higher triglyceride level (≥150 mg/dL), and higher homeostasis model assessment of insulin resistance (≥2.5) were not independently associated with rectal NETs, although these factors were more common in individuals with rectal NETs in the univariate analysis.

Conclusions: Young age (<50 years), male gender, alcohol drinking, and a low HDL-C level were risk factors for rectal NETs. Our results suggest that gender, behavioral factors, and dyslipidemia may affect the risk for developing rectal NETs.

Impact: The findings of this study contribute to a better understanding of the influence of gender, behavioral factors, and dyslipidemia in developing rectal NETs. Cancer Epidemiol Biomarkers Prev; 23(7); 1406–13. ©2014 AACR.
Bortezomib-Induced Unfolded Protein Response Increases Oncolytic HSV-1 Replication Resulting in Synergistic Antitumor Effects
Authors: Yoo Ji Young , Hurwitz Brian S. , Bolyard Chelsea , Yu Jun-Ge , Zhang Jianying , Selvendiran Karuppaiyah , Rath Kellie S. , He Shun , Bailey Zachary , Eaves David , Cripe Timothy P. , Parris Deborah S. , Caligiuri Michael A. , Yu Jianhua , Old Matthew , Kaur Balveen
Published: May 2014

Background: Bortezomib is an FDA-approved proteasome inhibitor, and oncolytic herpes simplex virus-1 (oHSV) is a promising therapeutic approach for cancer. We tested the impact of combining bortezomib with oHSV for antitumor efficacy.

Experimental Design: The synergistic interaction between oHSV and bortezomib was calculated using Chou–Talalay analysis. Viral replication was evaluated using plaque assay and immune fluorescence. Western blot assays were used to evaluate induction of estrogen receptor (ER) stress and unfolded protein response (UPR). Inhibitors targeting Hsp90 were utilized to investigate the mechanism of cell killing. Antitumor efficacy in vivo was evaluated using subcutaneous and intracranial tumor xenografts of glioma and head and neck cancer. Survival was analyzed by Kaplan–Meier curves and two-sided log-rank test.

Results: Combination treatment with bortezomib and oHSV (34.5ENVE), displayed strong synergistic interaction in ovarian cancer, head and neck cancer, glioma, and malignant peripheral nerve sheath tumor (MPNST) cells. Bortezomib treatment induced ER stress, evident by strong induction of Grp78, CHOP, PERK, and IRE1α (Western blot analysis) and the UPR (induction of hsp40, 70, and 90). Bortezomib treatment of cells at both sublethal and lethal doses increased viral replication (P < 0.001), but inhibition of Hsp90 ablated this response, reducing viral replication and synergistic cell killing. The combination of bortezomib and 34.5ENVE significantly enhanced antitumor efficacy in multiple different tumor models in vivo.

Conclusions: The dramatic synergy of bortezomib and 34.5ENVE is mediated by bortezomib-induced UPR and warrants future clinical testing in patients. Clin Cancer Res; 20(14); 3787–98. ©2014 AACR.
EW-7197, a Novel ALK-5 Kinase Inhibitor, Potently Inhibits Breast to Lung Metastasis
Authors: Son Ji Yeon , Park So-Yeon , Kim Sol-Ji , Lee Seon Joo , Park Sang-A. , Kim Min-Jin , Kim Seung Won , Kim Dae-Kee , Nam Jeong-Seok , Sheen Yhun Yhong
Published: May 2014

Advanced tumors produce an excessive amount of transforming growth factor β (TGFβ), which promotes tumor progression at late stages of malignancy. The purpose of this study was to develop anti-TGFβ therapeutics for cancer. We synthesized a novel small-molecule TGFβ receptor I kinase (activin receptor–like kinase 5) inhibitor termed N-[[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl]-2-fluoroaniline (EW-7197), and we investigated its potential antimetastatic efficacy in mouse mammary tumor virus (MMTV)/c-Neu mice and 4T1 orthotopic–grafted mice. EW-7197 inhibited Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice and 4T1 orthotopic–grafted mice. EW-7197 also inhibited the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic–grafted mice. Furthermore, EW-7197 enhanced cytotoxic T lymphocyte activity in 4T1 orthotopic–grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor–bearing mice. In summary, EW-7197 showed potent in vivo antimetastatic activity, indicating its potential for use as an anticancer therapy. Mol Cancer Ther; 13(7); 1704–16. ©2014 AACR.
Regulation of SRC Kinases by microRNA-3607 Located in a Frequently Deleted Locus in Prostate Cancer
Authors: Saini Sharanjot , Majid Shahana , Shahryari Varahram , Tabatabai Z. Laura , Arora Sumit , Yamamura Soichiro , Tanaka Yuichiro , Dahiya Rajvir , Deng Guoren
Published: May 2014

Genomic studies suggest that deletions at chromosome (chr) 5q region (particularly chr5q14-q23) are frequent in prostate cancer, implicating this region in prostate carcinogenesis. However, the genes within this region are largely unknown. Here, we report for the first time the widespread attenuation of miR-3607, an miRNA gene located at chr5q14 region, in prostate cancer. Expression analyses of miR-3607 in a clinical cohort of prostate cancer specimens showed that miR-3607 is significantly attenuated and low miR-3607 expression is correlated with tumor progression and poor survival outcome in prostate cancer. Our analyses suggest that miR-3607 expression may be a clinically significant parameter with an associated diagnostic potential. We examined the functional significance of miR-3607 in prostate cancer cell lines and found that miR-3607 overexpression led to significantly decreased proliferation, apoptosis induction, and decreased invasiveness. Furthermore, our results suggest that miR-3607 directly represses oncogenic SRC family kinases LYN and SRC in prostate cancer. In view of our results, we propose that miR-3607 plays a tumor-suppressive role in prostate cancer by regulating SRC kinases that in turn regulates prostate carcinogenesis. To our knowledge, this is the first report that: (i) identifies a novel role for miR-3607 located in a frequently deleted region of prostate cancer and (ii) defines novel miRNA-mediated regulation of SRC kinases in prostate cancer. Because SRC kinases play a central role in prostate cancer progression and metastasis and are attractive targets, this study has potential implications in the design of better therapeutic modalities for prostate cancer management. Mol Cancer Ther; 13(7); 1952–63. ©2014 AACR.
The PARP Inhibitors, Veliparib and Olaparib, Are Effective Chemopreventive Agents for Delaying Mammary Tumor Development in BRCA1-deficient Mice
Authors: To Ciric , Kim Eun-Hee , Royce Darlene B. , Williams Charlotte R. , Collins Ryan M. , Risingsong Renee , Sporn Michael B. , Liby Karen T.
Published: May 2014

Poly-ADP ribose polymerase (PARP) inhibitors are effective for the treatment of BRCA-deficient tumors. Women with these mutations have an increased risk of developing breast cancer and would benefit from effective chemoprevention. This study examines whether the PARP inhibitors, veliparib and olaparib, delay mammary gland tumor development in a BRCA1-deficient (BRCA1Co/Co;MMTV-Cre;p53+/−) mouse model. In dose de-escalation studies, mice were fed with control, veliparib (100 mg/kg diet), or olaparib (200, 100, 50, or 25 mg/kg diet) continuously for up to 43 weeks. For intermittent dosing studies, mice cycled through olaparib (200 mg/kg diet) for 2 weeks followed by a 4-week rest period on control diet. To examine biomarkers, mice were fed with olaparib using the intermittent dosing regimen and mammary glands were evaluated by immunohistochemistry. In mice treated with veliparib or olaparib (200 mg/kg diet), the average age of the first detectable tumor was delayed by 2.4 and 6.5 weeks, respectively, compared with controls. Olaparib also increased the average lifespan of mice by 7 weeks. In dose de-escalation studies, lower concentrations of olaparib delayed tumor development but were less effective than the highest dose. When fed intermittently, olaparib delayed the onset of the first palpable tumor by 5.7 weeks and significantly reduced proliferation and induced apoptosis in hyperplastic mammary glands. In summary, veliparib and olaparib are effective for delaying tumor development and extending the lifespan of BRCA1-deficient mice, and intermittent dosing with olaparib was as effective as continuous dosing. These results suggest that the use of PARP inhibitors is a promising chemopreventive option. Cancer Prev Res; 7(7); 698–707. ©2014 AACR.
Circulating microparticles in carriers of prothrombin G20210A mutation
Authors: Campello Elena , Spiezia Luca , Radu Claudia , Gavasso Sabrina , Zerbinati Patrizia , Woodhams Barry , Simioni Paolo
Published: May 2014

Factor V Leiden (FVL) and prothrombin gene mutation G20210A (PTM) are the two most common genetic polymorphisms known to predispose carriers to venous thromboembolism (VTE). A recent study in FVL carriers showed that circulating levels of microparticles (MP) may contribute to their thrombogenic profile. To further elucidate the prothrombotic state linked to genetic thrombophilia, we extended this study to carriers of PTM. The plasma level of annexin V-MP, endothelial- MP (EMP), platelet-MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) was measured in 124 carriers of PTM (105 heterozygous and 19 homozygous) and in 120 age- and gender-matched healthy individuals. Heterozygous and homozygous carriers of PTM showed significantly increased levels of annexin V-MP (2930 [1440–4646] MP/μl and 3064 [2412–4906] MP/μl, respectively) and significantly shorter PPL clotting time (54 [46–67] sec and 55 [46–64] sec) compared to controls (1728 [782–2122] MP/μl and 71 [61–75] sec, respectively; p<0.01). Similarly, heterozygous and homozygous subjects presented with significantly higher levels of EMP, PMP and TF+ than controls (p<0.05). PTM carriers with a VTE history had significantly higher MP numbers and activity than controls. No significant difference was seen between carriers with and without a VTE history. We conclude that the higher levels of circulating MP found in PTM carriers may play a role in the development of VTE possibly by increasing thrombin generation. Further studies are needed to better define the role of MP as triggering factors for the thrombotic complications characterizing mild genetic thrombophilic defects.
Evaluation of Interval Times From Onset to Reperfusion in Patients Undergoing Endovascular Therapy in the Interventional Management of Stroke III Trial
Authors: Goyal Mayank , Almekhlafi Mohammed A. , Fan Liqiong , Menon Bijoy K. , Demchuk Andrew M. , Yeatts Sharon D. , Hill Michael D. , Tomsick Thomas , Khatri Pooja , Zaidat Osama O. , Jauch Edward C. , Eesa Muneer , Jovin Tudor G. , Broderick Joseph P.
Published: May 2014

Background—

Meaningful delays occurred in the Interventional Management of Stroke (IMS) III trial. Analysis of the work flow will identify factors contributing to the in-hospital delays.

Methods and Results—

In the endovascular arm of the IMS III trial, the following time intervals were calculated: stroke onset to emergency department arrival; emergency department to computed tomography (CT); CT to intravenous tissue plasminogen activator start; intravenous tissue plasminogen activator start to randomization; randomization to groin puncture; groin puncture to thrombus identification; thrombus identification to start of endovascular therapy; and start of endovascular therapy to reperfusion. The effects of enrollment time, CT angiography use, interhospital transfers, and intubation on work flow were evaluated. Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture (median 84 minutes) and start of endovascular therapy to reperfusion (median 85 minutes). The CT to groin puncture time was significantly shorter during working hours than after. Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period. Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times. Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center. Age, sex, National Institutes of Health Stroke Scale score, and intubation did not affect delays.

Conclusions—

Important delays were identified before reperfusion in the IMS III trial. Delays decreased as the trial progressed. Use of CT angiography and endovascular treatment in the same center were associated with time savings. These data may help in optimizing work flow in current and future endovascular trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00359424.
Electrocardiographic Precordial ST‐Segment Deviations and the Risk of Cardiovascular Death: Results From the Copenhagen ECG Study
Authors: Rasmussen Peter Vibe , Nielsen Jonas Bille , Pietersen Adrian , Graff Claus , Lind Bent , Struijk Johannes Jan , Olesen Morten Salling , Haunsø Stig , Køber Lars , Svendsen Jesper Hastrup , Holst Anders Gaarsdal
Published: May 2014

Background

We sought to perform a study assessing the association between electrocardiographic
ST
‐segment deviations and cardiovascular death (
CVD
), in relation to sex and age (≥ and <65 years), in a large primary care population without overt ischemic heart disease.

Methods and Results

Using computerized analysis of
ECG
s from 285 194 persons, we evaluated the association between precordial
ST
‐segment deviations and the risk of
CVD
. All data on medication, comorbidity, and outcomes were retrieved from
D
anish registries. After a median follow‐up period of 5.8 years, there were 6679 cardiovascular deaths. Increasing
ST
‐depression was associated with an increased risk of
CVD
in almost all of the precordial leads, with the most robust association seen in lead V5 to V6.
ST
‐elevations in lead V2 to V6 were associated with increased risk of
CVD
in young women, but not in men. However,
ST
‐elevations in V1 increased the risk for both genders and age groups, exemplified by a
HR
of 1.80 (95%
CI
[1.19 to 2.74],
P
=0.005) for men <65 years with
ST
‐elevations ≥150 μV versus a nondeviating
ST
‐segment (−50 μV to +50 μV). In contrast, for men <65 years,
ST
‐elevations in lead V2 to V3 conferred a decreased risk of
CVD
with a
HR
of 0.77 (95%
CI
[0.62 to 0.96],
P
<0.001) for
ST
‐elevations ≥150 μV in V2.

Conclusion

We found that
ST
‐depressions were associated with a dose‐responsive increased risk of
CVD
in nearly all the precordial leads.
ST
‐elevations conferred an increased risk of
CVD
in women and with regard to lead V1 also in men. However,
ST
‐elevations in V2 to V3 were associated with a decreased risk of
CVD
in young men.
Carotid Intima‐Media Thickness is Associated With Incident Heart Failure Among Middle‐Aged Whites and Blacks: The Atherosclerosis Risk in Communities Study
Authors: Effoe Valery S. , Rodriguez Carlos J. , Wagenknecht Lynne E. , Evans Gregory W. , Chang Patricia P. , Mirabelli Maria C. , Bertoni Alain G.
Published: May 2014

Background

Increased carotid intima‐media thickness (
IMT
) is associated with subclinical left ventricular myocardial dysfunction, suggesting a possible role of carotid
IMT
in heart failure (
HF
) risk determination.

Methods and Results

Mean far wall carotid
IMT
, measured by B‐mode ultrasound, was available for 13 590 Atherosclerosis Risk in Communities study participants aged 45 to 64 years and free of
HF
at baseline.
HF
was defined using
ICD
‐9 428 and
ICD
‐10 I‐50 codes from hospitalization records and death certificates. The association between carotid
IMT
and incident
HF
was assessed using Cox proportional hazards analysis with models adjusted for demographic variables, major
CVD
risk factors, and interim
CHD
. There were 2008 incident
HF
cases over a median follow‐up of 20.6 years (8.1 cases per 1000 person‐years). Mean
IMT
was higher in those with
HF
than in those without (0.81 mm±0.23 versus 0.71 mm±0.17,
P
<0.001). Unadjusted rate of
HF
for the fourth compared with the first quartile of
IMT
was 15.4 versus 3.9 per 1000 person‐years;
P
<0.001. In multivariable analysis, after adjustment, each standard deviation increase in
IMT
was associated with incident
HF
(
HR
1.20 [95%
CI
: 1.16 to 1.25]). After adjustment, the top quartile of
IMT
was associated with
HF
(
HR
1.60 [95%
CI
: 1.37 to 1.87]). Results were similar across race and gender groups.

Conclusions

Increasing carotid
IMT
is associated with incident
HF
in middle‐aged whites and blacks, beyond risks explained by major
CVD
risk factors and
CHD
. This suggests that carotid
IMT
may be associated with
HF
through mechanisms different from myocardial ischemia or infarction.
Cyclooxygenases 1 and 2 Differentially Regulate Blood Pressure and Cerebrovascular Responses to Acute and Chronic Intermittent Hypoxia: Implications for Sleep Apnea
Authors: Beaudin Andrew E. , Pun Matiram , Yang Christina , Nicholl David D. M. , Steinback Craig D. , Slater Donna M. , Wynne‐Edwards Katherine E. , Hanly Patrick J. , Ahmed Sofia B. , Poulin Marc J.
Published: May 2014

Background

Obstructive sleep apnea (
OSA
) is associated with increased risk of cardiovascular and cerebrovascular disease resulting from intermittent hypoxia (
IH
)‐induced inflammation. Cyclooxygenase (
COX
)‐formed prostanoids mediate the inflammatory response, and regulate blood pressure and cerebral blood flow (
CBF
), but their role in blood pressure and
CBF
responses to
IH
is unknown. Therefore, this study's objective was to determine the role of prostanoids in cardiovascular and cerebrovascular responses to
IH
.

Methods and Results

Twelve healthy, male participants underwent three, 6‐hour
IH
exposures. For 4 days before each
IH
exposure, participants ingested a placebo, indomethacin (nonselective
COX
inhibitor), or Celebrex
®
(selective
COX
‐2 inhibitor) in a double‐blind, randomized, crossover study design. Pre‐ and post‐
IH
blood pressure,
CBF
, and urinary prostanoids were assessed. Additionally, blood pressure and urinary prostanoids were assessed in newly diagnosed, untreated
OSA
patients (n=33). Nonselective
COX
inhibition increased pre‐
IH
blood pressure (
P
≤0.04) and decreased pre‐
IH CBF
(
P
=0.04) while neither physiological variable was affected by
COX
‐2 inhibition (
P
≥0.90). Post‐
IH
,
MAP
was elevated (
P
≤0.05) and
CBF
was unchanged with placebo and nonselective
COX
inhibition. Selective
COX
‐2 inhibition abrogated the
IH
‐induced
MAP
increase (
P
=0.19), but resulted in lower post‐
IH CBF
(
P
=0.01). Prostanoids were unaffected by
IH
, except prostaglandin E
2
was elevated with the placebo (
P
=0.02). Finally,
OSA
patients had elevated blood pressure (
P
≤0.4) and
COX
‐1 formed thromboxane A
2
concentrations (
P
=0.02).

Conclusions

COX
‐2 and
COX
‐1 have divergent roles in modulating vascular responses to acute and chronic
IH
. Moreover,
COX
‐1 inhibition may mitigate cardiovascular and cerebrovascular morbidity in
OSA
.

Clinical Trial Registration

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01280006
Viewing Mount Laurel from Mount Zion: Theological Reflections on Social Integration
Authors: Brown Kevin , Stoddart Eric
Published: May 2014

Abstract

Racial segregation continues to be a staple of us social arrangements. However, the absence of a normative dimension to this phenomenon has allowed the value of segregation, or its conceptual opposite, integration to be determined by market forces. The result is that segregation is understood as an economic problem whose adverse effects can be ameliorated through efforts to integrate. We identify two primary problems with this approach. First, this conception risks bracketing out moral considerations related to exclusion. Secondly, under this paradigm, the rightness of integration is related to its consequence. In contrast, we argue for an inherent value to residential integration in itself and that a theological conception of relational autonomy can contribute to a more rich, morally engaged and motivating understanding of integration.
A Closed Marketplace: Religious Claims in the Public Square
Authors: Reynolds Terrence
Published: May 2014

Abstract

This article argues that the rules governing religious contributions to public debates are unnecessarily restrictive and grounded in a faulty understanding of the nature of all truth claims. After critically assessing the current limits on arguments made in the public domain, this study analyses the Ramsey Colloquium’s statement on ‘The Homosexual Movement’ as a paradigmatic illustration of the difficulties that accompany the public proclamation of religious convictions. It suggests that the rules currently governing cultural conversations marginalize distinctive religious contributions and call into question the reality of a genuine marketplace of ideas.
Further Sensitivities of Orographic Precipitation to Terrain Geometry in Idealized Simulations
Authors: Watson Campbell D. , Lane Todd P.
Published: May 2014

This study examines how variations to the nondimensional mountain height Ĥ and the horizontal aspect ratio β of a straight ridge and a concave ridge influence orographic precipitation. An idealized three-dimensional model is used to simulate a moist flow impinging upon these two ridges with Ĥ = 0.66–2.0 and β = 1.0–8.0. The concave ridge generates substantially more precipitation than the straight ridge via an established precipitation-enhancing funneling mechanism near the ridge vertex when the flow is unblocked. Based on previous work, it was hypothesized that when the approaching flow becomes blocked, the strength of the precipitation enhancement by the concave ridge relative to the straight ridge becomes negligible. This study reveals that, if Ĥ is sufficiently large to induce flow reversal on the windward slope, then a secondary circulation develops that is strengthened by the concave ridge with a subsequent enhancement of precipitation. It is also shown that the competing effects of the ridge length and width render the strength of the precipitation enhancement largely insensitive to β. A flow regime diagram for the straight ridge and the concave ridge is also constructed to illustrate the sensitivity of the critical Ĥ value for flow regime transition to changes in the terrain geometry; variations to the low-level relative humidity are also explored.
Some Observing System Simulation Experiments with a Hybrid 3DEnVAR System for Storm-Scale Radar Data Assimilation
Authors: Gao Jidong , Stensrud David J.
Published: May 2014

A hybrid three-dimensional ensemble–variational data assimilation (3DEnVAR) algorithm is developed based on the 3D variational data assimilation (3DVAR) and ensemble Kalman filter (EnKF) programs with the Advanced Regional Prediction System (ARPS). The method uses the extended control variable approach to combine the static and ensemble-derived flow-dependent forecast error covariances. The method is applied to the assimilation of simulated data from two radars for a supercell storm. Some sensitivity experiments are performed to answer questions about how flow-dependent covariance estimated from the forecast ensemble can be best used in the hybrid 3DEnVAR scheme. When the ensemble size is relatively small (with 5 or 10 ensemble members), it is found that experiments with a weaker weighting value for the ensemble covariance leads to better analysis results. Even when severe sampling errors exist, introducing ensemble-estimated covariances into the variational method still benefits the analysis. For reasonably large ensemble sizes (50–100 members), a stronger relative weighting (>0.8) for the ensemble covariance leads to better analyses from the hybrid 3DEnVAR. In addition, the sensitivity experiments also indicate that the best results are obtained when the number of the augmented control variables is a function of three spatial dimensions and ensemble members, and is the same for all analysis variables.
UM-SCC-103
Authors: Owen John H. , Hauff Samantha J. , Tang Alice L. , Graham Martin P. , Czerwinski Michael J. , Kaddoura Marcella , Papagerakis Silvana , Bradford Carol R. , Carey Thomas E. , Prince Mark E.P.
Published: May 2014

Objective:

A new head and neck cancer cell line was developed from a highly aggressive HNSCC of the oral cavity diagnosed in a 26-year-old pregnant woman.

Methods:

Cells from the primary tumor were passaged in culture and genotyped as a unique cell line. The resultant cell line was assessed for its ability to replicate the primary tumor.

Results:

The primary tumor and cell line contained 19.03% and 19.62% CD44high cells, respectively. CD44high cancer stem cells from UM-SCC-103 formed tumors after flank injections in mice that reconstituted the heterogeneity of the primary tumor. CD44 staining and histology in the primary tumor and tumors grown in vivo from the cell line were similar. CD44high cells from the primary tumor resulted in lung colony formation in 2 out of 2 tail vein injections in mice, whereas CD44low cells did not. Similarly, CD44high cells from UM-SCC-103 formed lung tumors in 2 out of 4 mice, whereas CD44low cells did not.

Conclusion:

The similarity in marker expression and tumorigenic behavior between the primary tumor and the resulting cell line strongly suggests that the cell line resembles the primary tumor that it was derived from and provides an important new research tool for the study of head and neck carcinomas in young patients.
Survivors’ experiences of return to work following cancer: A photovoice study
Authors: Morrison Tricia L. , Thomas Roanne L.
Published: May 2014

Background.

For many working-age cancer survivors, return to work represents a quality-of-life indicator. However, there is currently a lack of resources to assist survivors with navigating this process.

Purpose.

As a first step toward informing resources to address this gap, 10 female survivors’ return-to-work experiences were explored.

Method.

Photovoice methods were combined with interviews. Photographs and text were analyzed to identify key themes.

Findings.

Return to work was psychosocially motivated. Survivors independently decided if they would take leave and, if so, when they would return to work. Successful work reintegration was characterized as respectful, collaborative, and customized to each survivor’s ongoing limitations and variable recovery.

Implications.

The findings underscore a holistic, client-centred, and collaborative approach to successful return to work with cancer survivors. Occupational therapists, with their vocational rehabilitation knowledge and responsive practice philosophy, are well positioned to address this gap in survivorship support.
Becoming an occupational therapist: Perceived influence of international fieldwork placements on clinical practice
Authors: Haro Adriana V. , Knight Brittany P. , Cameron Debra L. , Nixon Stephanie A. , Ahluwalia Puja A. , Hicks Emma L.
Published: May 2014

Background.

Many occupational therapy programs have augmented curricula to provide students with opportunities to engage in international fieldwork placements (IFPs). However, limited research exists exploring the perceived influence that IFPs may have on future occupational therapy roles and characteristics.

Purpose.

The purpose of this study is to explore how Canadian occupational therapists who participated in IFPs as students perceive the influence of their IFP experience on their subsequent practice.

Method.

Semi-structured interviews were conducted with 20 occupational therapists who participated in IFPs as occupational therapy students. The interview guide was developed based on the Profile of Occupational Therapy Practice in Canada and relevant literature. A directed content analysis was used in conjunction with the DEPICT model of data analysis to guide the analysis process and summarize the results.

Findings.

Participants described how IFPs nurtured the development of six skills, or active ingredients, which supported the development of competence in occupational therapy roles. IFPs were also perceived as providing a competitive edge.

Implications.

This study suggests that IFPs shape the development of competence in key practice skills and occupational therapy roles.
Payment Analysis of Two Diagnosis and Management Approaches of Acute Otitis Media
Authors: Casey Janet R. , Pichichero Michael E.
Published: May 2014

We determined the cost of care for 2 diagnosis and management approaches for acute otitis media (AOM) among children 6 to 30 months old. A case–control design was used. Cases included 208 children diagnosed with AOM based on a bulging tympanic membrane (TM) and treated with amoxicillin/clavulanate. Controls (5:1 ratio) included 1020 children with AOM diagnosed not requiring bulging of the TM and treated with amoxicillin. Fewer cases (49%) than controls (69%) were diagnosed with AOM ( P < .001), fewer were diagnosed with recurrent AOM or AOM treatment failure (0.34 vs 1.6/child; P < .0001), and fewer had insertion of tympanostomy tubes (6.3% vs 14.8%) due to recurrent AOM ( P < .0001). The combined direct payments and indirect costs for management of AOM were $539/case versus $1,023/control. Using Rochester NY payments generalized to the US birth cohort, this case diagnosis and treatment strategy could save $1.008 billion per year.
Constructing the gendered body? A critical discourse analysis of gender equality schemes in the health sector in England
Authors: Payne Sarah
Published: May 2014

This article examines gender discourses embedded in gender equality policies in the health sector. Gender mainstreaming was first adopted by a number of international and intergovernmental, regional and national actors some time ago, yet there is limited evidence of progress in addressing gender justice in health. Failures in gender equality policies have often been attributed to the lack of gender-disaggregated data, combined with a lack of resources, training and skills. In addition, studies have identified problems originating in the shift from participatory approaches to technocratic solutions, and the persistence of underlying gender relations of power. However, gender equality policies may also contribute to gender discourse in ways which reinforce and perpetuate inequalities between men and women. This article draws on Bacchi’s ‘what is the problem represented to be’ (WPR) approach to policy analysis, to explore responses of primary care organisations in England to legislation requiring public sector organisations to tackle gender discrimination and promote equality of opportunity between men and women. The article adopts a critical discourse approach to gender equality documents and suggests that such texts construct women and men as essentially different, reinforcing specific forms of masculinity and male performance and notions of male disadvantage in health systems.
Simultaneous optimization of the mechanical properties of postconsumer natural fiber/plastic composites: Processing analysis
Authors: Toupe Jean Luc , Trokourey Albert , Rodrigue Denis
Published: May 2014

In this work, manufacturing steps of composites were simultaneously analyzed to optimize four mechanical properties (flexural and tensile moduli, impact strength, and tensile stress at yield) of flax fiber/postconsumer recycled plastic composite. Eight parameters of the extrusion-injection process (extrusion: temperature profile and screw speed; injection: temperature profile in the barrel, mold temperature, injection speed, injection pressure, injection time, and back pressure) were selected. Process optimization, taking into account simultaneously all the mechanical properties (multi-responses optimization), required four steps: determination of influential factors by a screening design and an evaluation of the selected factors effects on the mechanical properties, modeling of the relationships between mechanical properties and significant factors by a Box–Behnken experimental design and a multiple linear regression analysis, identification of the potentially optimum conditions using the desirability function approach (Derringer–Suich model), and determination the optimum composite manufacturing conditions by a comparative analysis of the material relative qualities.
Virtual city: An individual-based digital environment for human mobility and interactive behavior
Authors: Ge Yuanzheng , Meng Rongqing , Cao Zhidong , Qiu Xiaogang , Huang Kedi
Published: May 2014

Increasing computing capability and high-resolution digital tracing of human behavior make large-scale computational models for individual-based realistic simulation available. Reconstructing a virtual computational environment is crucial for designing and implementing individual interactions in an artificial society as human beings behave in the real world. In this paper, we propose a methodology to recreate a virtual city by utilizing statistical data and geographic information. The synthetic population and physical environment are baseline components of the virtual city. Individual-based modeling is used to specify individuals’ demographic characteristics, and each individual is endowed with heterogeneous social attributes. Various physical environments are generated with geographic locations and mapped with individuals to support daily mobility, migration, and interaction. A series of algorithms are proposed to bridge the gap between macroscopic data and microscopic models, and guarantee equivalence between them. Based on the methodology, we reconstructed a virtual city of Beijing, and presented the statistical analysis of population structure, spatial distribution of physical environments, human travel characteristics, and spatial topologies of social networks. Our synthetic population can represent individual actors in the form of households and household members, and the synthetic population is statistically equivalent to a real population. The proposed methodology is efficient to recreate a synthetic virtual city and can serve as a base for computational experiments.
Mundane objects in the city: Laundry practices and the making and remaking of public/private sociality and space in London and New York
Authors: Watson Sophie
Published: May 2014

The paper considers how shifting laundry practices and technologies associated with dirty washing have over time summoned different spaces, socialities and socio-spatial assemblages in the city, enrolling different actors and multiple publics and constituting different associations, networks and relations in its wake as it travels from the home and back again. It argues that rather than being an inert object of unpleasant matter, whose encounter with humans has been largely restricted to certain categories of person for its transformation to re-use, and thus passed unnoticed, the paper explores how laundry practices have figured in producing and reproducing gendered (and classed) relations of labour, and enacting multiple socio-spatial, and gendered, relations and assemblages in the city, which have largely gone unnoticed in accounts of everyday urban life.