bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Birth Size and Catch-Up Growth on Adult Blood Pressure and Carotid Intima-Media Thickness
Authors: Leunissen R.W.J. , Kerkhof G.F. , Stijnen T. , Hokken-Koelega A.C.S.
Published: July 2012

Aims: To investigate the effect of birth size and weight gain during childhood on blood pressure and carotid intima-media thickness (cIMT) in young adulthood. Methods: The relationship of birth size with systolic blood pressure (SBP), diastolic blood pressure (DBP), and cIMT was investigated in 243 adults, aged 18–24 years. SBP, DBP, and cIMT were also analyzed in 4 subgroups: subjects either born small for gestational age with short stature (SGA-S) or with catch-up growth (SGA-CU), or born appropriate for gestational age with idiopathic short stature or with normal stature (controls). Results: Adult weight SDS and fat mass were positively related to SBP and DBP, adjusted for birthweight SDS which was not related to SBP and DBP. Birth size was also not related to cIMT. Subgroup analyses showed no differences in blood pressure between subgroups, but cIMT was significantly greater in SGA-CU subjects than in controls after correction for age, gender and artery diameter. This difference became borderline significant after additional correction for smoking and SBP. Conclusion: Not birth size but childhood weight gain, especially fat mass, determines young adult blood pressure. Postnatal catch-up growth appears to have a greater influence on cardiovascular disease markers than birth size.
Low Serum Adiponectin Levels in Korean Children with a Family History of Type 2 Diabetes Mellitus
Authors: Oh Yeon Joung , Nam Hyo-Kyoung , Rhie Young Jun , Park Sang Hee , Lee Kee-Hyoung
Published: July 2012

Background/Aims: The current worldwide increases of type 2 diabetes mellitus (T2DM) in children coincide with increases in the prevalence of obesity. We investigated the insulin resistance and adiponectin levels of children and adolescents with a family history of T2DM (FHD). Methods: Our sample included 131 children and adolescents aged 8–15 years. Fasting plasma glucose, lipids, fasting insulin, adiponectin levels and HOMA-IR were analyzed according to FHD and obesity. Oral glucose tolerance tests were performed in all subjects except non-obese subjects without FHD. Results: Adiponectin levels of subjects with FHD were significantly lower than those of subjects without FHD in both the obese and nonobese groups. HOMA-IR was significantly higher in obese subjects with FHD than in those without FHD. Adiponectin levels were found to be independently associated with FHD and Matsuda index. The frequency of impaired glucose tolerance in obese subjects with FHD was more than four times higher compared to obese subjects without FHD. Conclusion: Our results suggest that FHD could be a risk factor of T2DM in obese Korean children, especially with low serum levels of adiponectin.
Ticagrelor FDA Approval Issues Revisited
Authors: Serebruany Victor L.
Published: July 2012

Context: On July 20, 2011, the Food and Drug Administration (FDA) approved ticagrelor (Brilinta™) for use during acute coronary syndromes. The drug labeling includes a ‘black box’ warning for bleeding risks, conventional for antithrombotics, and a unique warning that higher than 100 mg/daily maintenance treatment with aspirin may reduce ticagrelor effectiveness. The approval was granted following ticagrelor secondary reviews, and review of complete response by FDA officials. Objective: To summarize the recommendations of different FDA reviewers, and their impact on drug approval. Design, Setting, and Patients: Review of the Platelet Inhibition and Clinical Outcomes (PLATO) trial comparing the efficacy of ticagrelor versus standard care treatment with clopidogrel. Patients (n = 18,624) with moderate- to high-risk acute coronary syndromes undergoing coronary intervention or being medically managed were randomized to ticagrelor (180-mg loading dose followed by 90 mg twice daily thereafter) or clopidogrel (300–600-mg loading dose followed by 75 mg once daily) for 6–12 months. Results: The facts outlined in official reviews suggest that ticagrelor has been approved despite objections from both clinical primary reviewers assessing drug efficacy and safety. In addition, the statistical reviewer and cross-discipline team leader also recommended against approval. The putative grounds for their concerns were retrieved from the public FDA records and are briefly outlined here.
Bimonthly Regimen of High-Dose Leucovorin, Infusional 5-Fluorouracil, Epirubicin and Cisplatin (Modified ECF) as Adjuvant Chemotherapy in Resected Gastric Adenocarcinoma
Authors: Unek Ilkay Tugba , Unek Tarkan , Oztop Ilhan , Akman Tulay , Atilla Koray , Ellidokuz Hulya , Bora Seymen , Sarioglu Sulen , Yilmaz Ugur
Published: July 2012

Background: The administration of the de Gramont regimen in combination with cisplatin and epirubicin (modified ECF) has previously been reported as a treatment for advanced gastric cancer, but here we report this regimen combination in an adjuvant setting for the first time. Methods: Forty-eight patients with curatively resected gastric cancer were treated. Each 2-week cycle consisted of epirubicin (50 mg/m2), cisplatin (50 mg/m2), 5-fluorouracil (5-FU) IV bolus (400 mg/m2) and 5-FU IV (2,400 mg/m2) over 46 h plus leucovorin IV (400 mg/m2) over 2 h. Postoperative chemoradiotherapy was also administered to the patients when indicated. We retrospectively reviewed the patients who were treated with modified ECF. Results: The median disease-free survival (DFS) was 40.7 months and the 1-, 3- and 5-year DFS rates were 78.5, 55.7 and 44.6%, respectively. The most common grade 3–4 toxicities were hematological and gastrointestinal. Conclusion: A modified ECF regimen may be an effective and convenient treatment with tolerable toxicities for the adjuvant treatment of gastric cancer. It may provide an alternative regimen to the standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient.
Regulation of Overnutrition-Induced Cardiac Inflammatory Mechanisms by nebivolol
Authors: Gul Rukhsana , DeMarco Vincent G. , Sowers James R. , Whaley-Connell Adam , Pulakat Lakshmi
Published: July 2012

Background: Unlike conventional β-blockers, nebivolol, a third-generation β-adrenergic receptor blocker with vasodilator properties, promotes insulin sensitivity. Objective: The objective of this study was to determine whether nebivolol regulates overnutrition-induced activation of cardiac nutrient sensor kinases and inflammatory signaling. Methods: Young Zucker obese (ZO) rats, a rodent model for overnutrition, and age-matched Zucker lean rats were treated with nebivolol (10 mg/kg/day; 21 days) and cardiac function was monitored by echocardiography and pressure volume loop analysis. Activation status of nutrient sensor serine/threonine kinases mammalian target for rapamycin (mTOR), and p70 S6kinase (S6K1) and S6K1-substrate RPS6, inflammatory marker Janus kinase 2 (Jak2) and its substrate STAT1, and energy sensor AMP-dependent kinase (AMPK) were monitored by determining phosphorylation status of pSer2448 of mTOR, pThr389 of S6K1, pSer235/236 of RPS6, pTyr1007/1008 of Jak2, pTyr701 of STAT1, and pThr172 of AMPK, respectively. Results: Nebivolol reduced weight and improved cardiac function of ZO rats as shown by improvements in the myocardial performance index and a decrease in the diastolic parameter tau (τ), the time constant of isovolumic relaxation. Nebivolol also attenuated excessive activation of the nutrient sensor kinases mTOR and S6K1 and their substrate RPS6 as well as the inflammatory marker Jak2 and substrate STAT1 in ZO myocardium (p < 0.05). Moreover, nebivolol reversed suppression of the energy sensor kinase AMPK in ZO hearts (p < 0.05). Conclusion: We report for the first time that nebivolol regulates overnutrition-induced activation of cardiac mTOR and Jak/STAT signaling and reverses suppression of AMPK. Since it also suppresses weight gain, nebivolol appears effective in the treatment of overnutrition-related cardiac inflammation and diastolic dysfunction.
Response to Growth Hormone Therapy in Children with Noonan Syndrome: Correlation with or without PTPN11 Gene Mutation
Authors: Choi Jin-Ho , Lee Beom Hee , Jung Chang-Woo , Kim Yoo-Mi , Jin Hye Young , Kim Jae-Min , Kim Gu-Hwan , Hwang Jin Soon , Yang Sei Won , Lee Jin , Yoo Han-Wook
Published: July 2012

Background/Aims: The objective of this study was to evaluate the efficacy of recombinant human growth hormone (rhGH) therapy and the influence of genotype on the response to rhGH therapy in children with Noonan syndrome (NS). Methods: 14 male and 4 female subjects with NS with short stature, whose height was <3rd percentile, were included. The rhGH was subcutaneously administered at a dose of 66 µg/kg/day. Mutations in the PTPN11 gene were identified in 10 subjects (55.6%). Mutations in the SOS1 (2 children, 11.1%), MEK1 (1 child, 5.6%) and KRAS (1 child, 5.6%) genes were also found. Results: Height SDS increased from –2.8 ± 0.9 at the start of rhGH therapy to –2.0 ± 0.9 12 months later (p < 0.001). Height velocity increased from 5.0 ± 0.9 cm/year in the year before treatment to 8.9 ± 1.6 during treatment (p < 0.001). Changes in height SDS, height velocity, and serum IGF-1 level did not differ significantly between those children with or without PTPN11 mutations. Conclusion: The rhGH therapy significantly improved the growth velocity and increased the serum IGF-1 level. Long-term correlation between genotype and rhGH therapy responsiveness needs to be addressed in a large population.
Nonallergic Drug Hypersensitivity Reactions
Authors: Farnam Kevin , Chang Christopher , Teuber Suzanne , Gershwin M. Eric
Published: July 2012

Background: Nonallergic drug hypersensitivities, also referred to as pseudoallergic or anaphylactoid reactions, have clinical manifestations that are often indistinguishable from allergic reactions. Methods: We performed a PubMed search using the terms ‘drug allergy, drug hypersensitivity, pseudoallergies, anaphylaxis and nonallergic drug reactions’ and reviewed 511 publications dated between 1970 and 2012. A total of 160 papers that were relevant to the most common nonallergic drug hypersensitivity reactions were selected for discussion. Results: Nonallergic drug hypersensitivities do not involve either IgE-mediated (type 1) or delayed (type 4) hypersensitivity. Nonallergic hypersensitivities are commonly referred to as pseudoallergic or idiosyncratic reactions. The common nonallergic drug hypersensitivities are secondary to chemotherapeutic drugs, radiocontrast agents, vancomycin, nonsteroidal anti-inflammatory agents, local anesthetic reactions and opiates. Protocols for skin testing of radiocontrast, nonsteroidal anti-inflammatory agents, local anesthetics and chemotherapeutic agents have been developed, though most have not been validated or standardized. Other diagnostic tests include in vitro-specific IgE tests, and the current ‘gold’ standard is usually an oral challenge or bronchoprovocation test. In the case of aspirin, even though it is not believed to be IgE-mediated, a ‘desensitization’ protocol has been developed and utilized successfully, although the mechanism of this desensitization is unclear. Conclusions: Diagnostic methods exist to distinguish allergic from nonallergic drug hypersensitivity reactions. The best option in nonallergic drug hypersensitivity is avoidance. If that is not possible, premedication protocols have been developed, although the success of premedication varies amongst drugs and patients.
Identification of Two DNA Helicases UvrD and DinG as Suppressors for Lethality Caused by Mutant cspA mRNAs
Authors: Hwang Jihwan , Lee Kangseok , Phadtare Sangita , Inouye Masayori
Published: July 2012

CspA is a major cold shock-inducible protein (70 aa), and its major role in the cold shock response was shown to be as an RNA chaperone destabilizing secondary structure of mRNAs at low temperature. Previously, we showed that the overexpression of mutant cspA containing premature non-sense codons at various positions led to stalled ribosomes on mutant cspA transcripts, ultimately leading to cell death. This lethality is primarily due to the highly translatable cspA 5′-UTR that recruits most of the ribosomes from other mRNAs, which are then stalled at the abnormal stop codon. This was called the ‘LACE’ effect. We show here that non-sense mutation even at the 67th position as well as substitutions of aromatic amino acid residues present on the RNA-binding surface of CspA protein to alanine caused the LACE effect by trapping a substantial amount of ribosomes on cspA mRNAs. In an attempt to identify a suppressor(s), which may help the cells to recover from the inhibitory LACE effect, genetic screening of an Escherichia coli genomic library was performed. We isolated suppressors that contained the genomic fragments encoding uvrD and dinG, respectively, whose gene products are ATP-dependent DNA helicases. The nucleic acid-binding and ATPase activities of these two helicases were found to be essential for their suppression activity. This genomic screening offers an approach to shed light on the mechanistic of 5′-UTR of cspA mRNA and novel roles of E. coli helicases that function in DNA repair.
Vitamin D and Parathyroid Hormone Relationships with Urinary Nitric Oxide Metabolites and Plasma Isoprostanes in African-Americans
Authors: Valiña-Tóth Anna Liza , Lai Zongshan , Zhang Shilling , Flack John M.
Published: July 2012

Background: Vitamin D deficiency and secondary rises in parathyroid hormone (PTH) are highly prevalent in obese African-Americans. Endothelial dysfunction related to oxidative stress is more common in African-Americans compared to whites. Currently, the association of vitamin D (25-hydroxyvitamin D, 25-OH D) and PTH to nitric oxide metabolites (NOx) – nitrate and nitrite – and oxidative stress in African-Americans is unknown. Objective: A cross-sectional design was utilized to determine the association of 25-OH D and PTH with urinary NOx (UNOx) (n = 101) and plasma isoprostanes (n = 125), an oxidative stress marker, in overweight (body mass index of 25–39.9), normotensive African-Americans aged ≥35 years. Measurements: Multivariable linear regression analysis adjusted for age, sex, body mass index, and season was used to determine the relationship of 25-OH D and PTH to UNOx and isoprostanes. General linear models, adjusted for the same covariates, contrasted UNOx across three mutually exclusive vitamin D/PTH groups: (1) normal 25-OH D (51–249 nmol/l) and normal PTH (≤65 pg/ml); (2) low 25-OH D and normal PTH, and (3) low 25-OH D and high PTH. Results: 25-OH D was directly associated with UNOx before (p = 0.02) and after (p = 0.03) adjustment for PTH levels. A borderline significant association was observed between PTH and isoprostanes (p = 0.08). UNOx was 424, 290, and 270 µmol/8 h, respectively, across vitamin D/PTH groups 1–3 (p = 0.08). Conclusion: 25-OH D was directly associated with NO availability and PTH was positively, though borderline, associated with isoprostanes in overweight, normotensive adult African-Americans.
Demographics, Trends, and Outcomes in Pediatric Acute Myocarditis in the United States, 2006 to 2011
Authors: Ghelani Sunil J. , Spaeder Michael C. , Pastor William , Spurney Christopher F. , Klugman Darren
Published: July 2012

Background—

There is a lack of clear diagnostic and management guidelines for acute myocarditis in the pediatric population. We used a multi-institutional database to characterize demographics, practice variability, and outcomes in this population.

Methods and Results—

Patients with acute myocarditis (n=514) were identified from April 2006 to March 2011 using the Pediatric Health Information System database, and regional variations in management and outcomes were analyzed. Ninety-seven patients (18.9%) received extracorporeal membrane oxygenation, 22 (4.3%) received ventricular assist device, 21 (4.1%) received heart transplantation, and 37 (7.2%) died. Of the 104 patients who received extracorporeal membrane oxygenation or ventricular assist device, 17 (16.3%) had heart transplantation, 25 (24%) died, and 62 (59.6%) showed recovery of myocardial function. There was a decrease in the use of endomyocardial biopsy (
P
=0.03) and an increase in the use of magnetic resonance imaging (
P
<0.01) over the study period. Although the use of medications and procedures varied between different regions, the occurrence of death or heart transplantation showed no significant regional associations. The use of extracorporeal membrane oxygenation (odds ratio, 5.8; 95% confidence interval, 2.9–11.4;
P
<0.01), ventricular assist device (odds ratio, 8.2; 95% confidence interval, 2.7–24.9;
P
<0.01), and vasoactive medications (odds ratio, 5.7; 95% confidence interval, 1.2–26.1;
P
=0.03) was independently associated with death/transplantation.

Conclusions—

There is significant temporal and regional variation in the diagnostic modalities and management used for pediatric myocarditis, which continues to have high morbidity and mortality. Extracorporeal membrane oxygenation, ventricular assist device, and vasoactive medications are independently associated with increased mortality/transplantation.
Variability in Surgeons’ Perioperative Practices May Influence the Incidence of Low-Output Failure After Coronary Artery Bypass Grafting Surgery
Authors: Likosky Donald S. , Goldberg Joshua B. , DiScipio Anthony W. , Kramer Robert S. , Groom Robert C. , Leavitt Bruce J. , Surgenor Stephen D. , Baribeau Yvon R. , Charlesworth David C. , Helm Robert E. , Frumiento Carmine , Sardella Gerald L. , Clough Robert A. , MacKenzie Todd A. , Malenka David J. , Olmstead Elaine M. , Ross Cathy S. ,   for the Northern New England Cardiovascular Disease Study Group
Published: July 2012

Background—

Postoperative low-output failure (LOF) is an important contributor to morbidity and mortality after coronary artery bypass grafting surgery. We sought to understand which pre- and intra-operative factors contribute to postoperative LOF and to what degree the surgeon may influence rates of LOF.

Methods and Results—

We identified 11 838 patients undergoing nonemergent, isolated coronary artery bypass grafting surgery using cardiopulmonary bypass by 32 surgeons at 8 centers in northern New England from 2001 to 2009. Our cohort included patients with preoperative ejection fractions >40%. Patients with preoperative intraaortic balloon pumps were excluded. LOF was defined as the need for ≥2 inotropes at 48 hours, an intra- or post-operative intraaortic balloon pumps, or return to cardiopulmonary bypass (for hemodynamic reasons). Case volume varied across the 32 surgeons (limits, 80–766; median, 344). The overall rate of LOF was 4.3% (return to cardiopulmonary bypass, 2.6%; intraaortic balloon pumps, 1.0%; inotrope usage, 0.8%; combination, 1.0%). The predicted risk of LOF did not differ across surgeons,
P
=0.79, and the observed rates varied from 1.1% to 10.2%,
P
<0.001. Patients operated by low-rate surgeons had shorter clamp and bypass times, antegrade cardioplegia, longer maximum intervals between cardioplegia doses, lower cardioplegia volume per anastomosis or minute of ischemic time, and less hot-shot use. Patients operated on by higher LOF surgeons had higher rates of postoperative acute kidney injury.

Conclusions—

Rates of LOF significantly varied across surgeons and could not be explained solely by patient case mix, suggesting that variability in perioperative practices influences risk of LOF.
A Comprehensive Evaluation of Rhythm Monitoring Strategies for the Detection of Atrial Fibrillation Recurrence
Authors: Charitos Efstratios I. , Stierle Ulrich , Ziegler Paul D. , Baldewig Malte , Robinson Derek R. , Sievers Hans-Hinrich , Hanke Thorsten
Published: July 2012

Background—

Intermittent rhythm monitoring (IRM) to detect atrial fibrillation (AF) recurrence is employed to evaluate the success of therapeutic interventions. In a large population of patients with continuous monitoring (CM), we investigated the sensitivity of various frequencies and durations of IRM strategies on the detection of AF recurrence, the dynamics behind AF recurrence detection, and we describe measures to evaluate temporal AF recurrence.

Methods and Results—

Rhythm histories of 647 patients (mean AF burden, 0.12±0.22; median, 0.014; 687 patient-years) with implantable CM devices were reconstructed and analyzed. With the use of computationally intensive simulation, the sensitivity of IRM of various frequencies and durations on the identification of AF recurrence was evaluated. Prolonged-duration IRM was superior to shorter IRM (
P
<0.0001). However, even with aggressive IRM strategies, AF recurrence was not detected in a great proportion of patients. The temporal AF burden aggregation (AF density) was directly related to IRM sensitivity (
P
<0.0001). Even at similar AF burdens, patients with high-density AF required higher-frequency or prolonged-duration IRM to achieve the same sensitivity as in low-density AF (
P
<0.0001). Patients with high-density, low-burden AF benefit the most from CM for detection of AF recurrence.

Conclusions—

IRM follow-up is significantly inferior to CM. IRM strategies will not identify AF recurrence in a great proportion of patients at risk. Temporal AF characteristics play a significant role in AF recurrence detection with the use of IRM. For the scientific, evidence-based evaluation of AF treatments, CM should be strongly recommended. Prospective studies are required to evaluate whether CM to guide clinical management can also improve patient outcomes.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00806689.
Comparison of Everolimus-Eluting and Sirolimus-Eluting Coronary Stents
Authors: Kimura Takeshi , Morimoto Takeshi , Natsuaki Masahiro , Shiomi Hiroki , Igarashi Keiichi , Kadota Kazushige , Tanabe Kengo , Morino Yoshihiro , Akasaka Takashi , Takatsu Yoshiki , Nishikawa Hideo , Yamamoto Yoshito , Nakagawa Yoshihisa , Hayashi Yasuhiko , Iwabuchi Masashi , Umeda Hisashi , Kawai Kazuya , Okada Hisayuki , Kimura Kazuo , Simonton Charles A. , Kozuma Ken
Published: July 2012

Background—

Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization.

Methods and Results—

Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (
P
noninferiority
<0.0001, and
P
superiority
=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%,
P
=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm,
P
noninferiority
<0.0001, and
P
superiority
=0.24) at 278±63 days after index stent implantation.

Conclusions—

One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01035450.
Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure
Authors: López Begoña , Querejeta Ramón , González Arantxa , Larman Mariano , Díez Javier
Published: July 2012

We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. The expression of lysyl oxidase (LOX), which regulates CCL, was assessed by Western blot. Compared with patients with normal pulmonary capillary wedge pressure (≤12 mm Hg; n=16), patients with elevated pulmonary capillary wedge pressure (>12 mm Hg; n=22) exhibited increases of left ventricular chamber stiffness constant, fraction of myocardial volume occupied by total collagen tissue, fraction of myocardial volume occupied by collagen type I fibers, CCL, insoluble stiff collagen, and LOX. Pulmonary capillary wedge pressure was correlated with left ventricular chamber stiffness constant (
r
=0.639;
P
<0.001), insoluble stiff collagen (
r
=0.474;
P
<0.005), CCL (
r
=0.625;
P
<0.001), and LOX (
r
=0.410;
P
<0.05) in all of the patients but not with fraction of myocardial volume occupied by total collagen tissue or fraction of myocardial volume occupied by collagen type I fibers. In addition, CCL was correlated with insoluble stiff collagen (
r
=0.612;
P
<0.005), LOX (
r
=0.538;
P
<0.01), left ventricular chamber stiffness constant (
r
=0.535;
P
<0.005), peak filling rate (
r
=−0.343;
P
<0.05), ejection fraction (
r
=−0.430;
P
<0.01), and amino-terminal propeptide of brain natriuretic peptide (
r
=0.421;
P
<0.05) in all of the patients. These associations were independent of confounding factors. These findings indicate that, in hypertensive patients with stage C heart failure, it is only the quality of collagen (ie, degree of cross-linking) that associates with elevated filling pressures. It is suggested that LOX-mediated excessive CCL facilitates the increase in left ventricular stiffness with the resulting elevation of filling pressures in these patients.
Renal Resistive Index and Cardiovascular and Renal Outcomes in Essential Hypertension
Authors: Doi Yohei , Iwashima Yoshio , Yoshihara Fumiki , Kamide Kei , Hayashi Shin-ichirou , Kubota Yoshinori , Nakamura Satoko , Horio Takeshi , Kawano Yuhei
Published: July 2012

Increased renal restive index (RI) measured using Doppler ultrasonography has been shown to correlate with the degree of renal impairment in hypertensive patients. We investigated the prognostic role of RI in cardiovascular and renal outcomes. A total of 426 essential hypertensive subjects (mean age, 63 years; 50% female) with no previous cardiovascular disease were included in this study. Renal segmental arterial RI was measured by duplex Doppler ultrasonography. During follow-up (mean, 3.1 years), 57 participants developed the primary composite end points including cardiovascular and renal outcomes. In multivariate Cox regression analysis, RI was an independent predictor of worse outcome in total subjects (hazard ratio, 1.71 for 1 SD increase), as well as in patients with estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m
2
(hazard ratio, 2.11 for 1 SD increase;
P
<0.01, respectively). When divided into 4 groups based on the respective sex-specific median levels of RI in the eGFR ≥60 and eGFR <60 mL/min per 1.73 m
2
groups, the group with eGFR <60 and high RI (male ≥0.73, female ≥0.72) had a significantly poorer event-free survival rate (χ
2
=126.4;
P
<0.01), and the adjusted hazard ratio by multivariate Cox regression analysis was 9.58 (95% CI, 3.26–32.89;
P
<0.01). In conclusion, impairment of renal hemodynamics evaluated by increased RI is associated with an increased risk of primary composite end points, and the combination of high RI and low eGFR is a powerful predictor of these diseases in essential hypertension. In hypertensive patients with chronic kidney disease, RI evaluation may complement predictors of cardiovascular and renal outcomes.
Patients With Continuous-Flow Left Ventricular Assist Devices Provide Insight in Human Baroreflex Physiology
Authors: Tank Jens , Heusser Karsten , Malehsa Doris , Hegemann Katrin , Haufe Sven , Brinkmann Julia , Tegtbur Uwe , Diedrich André , Bara Christoph , Jordan Jens , Strüber Martin
Published: July 2012

The superior clinical outcome of new continuous-flow left ventricular assist devices (LVADs) challenges the physiological dogma that cardiovascular autonomic homeostasis requires pulsatile blood flow and pressure. We tested the hypothesis that continuous-flow LVADs impair baroreflex control of sympathetic nerve traffic, thus further exacerbating sympathetic excitation. We included 9 male heart failure patients (26–61 years; 18.9–28.3 kg/m
2
) implanted with a continuous-flow LVAD. We recorded ECG, respiration, finger blood pressure, brachial blood pressure, and muscle sympathetic nerve activity. After baseline measurements had been taken, patients underwent autonomic function testing including deep breathing, a Valsalva maneuver, and 15° head-up tilt. Finally, we increased the LVAD speed in 7 patients. Spontaneous sympathetic baroreflex sensitivity was analyzed. Brachial blood pressure was 99±4 mm Hg with 14±2 mm Hg finger pulse pressure. Muscle sympathetic nerve activity bursts showed a normal morphology, were linked to the cardiac cycle, and were suppressed during blood pressure increases. Mean burst frequency was lower compared with age- and body mass index–matched controls in 2 patients, slightly increased in 4 patients, and increased in 2 patients (
P
=0.11). Muscle sympathetic nerve activity burst latency and the median values of the burst amplitude distribution were similar between groups. Muscle sympathetic nerve activity increased 4±1 bursts per minute with head-up tilt (
P
<0.0003) and decreased 3±4 bursts per minute (
P
<0.031) when LVAD speed was raised. The mean sympathetic baroreflex slope was −3.75±0.79%/mm Hg in patients and −3.80±0.55%/mm Hg in controls. We conclude that low pulse pressure levels are sufficient to restrain sympathetic nervous system activity through baroreflex mechanisms.
Distribution of Graupel and Hail With Size
Authors: AUER AUGUST H.
Published: July 2012

Observations have been made on the size and concentration of graupel and hail occurring in untreated convective cloud systems over the High Plains of the United States. From these data, an average graupel and hail distribution has been generated. The comparison of this .,ize spectrum with data from other studies, along with the implications to hail detection and hail suppression, is also discussed.
A multiscale modeling approach to analyze filament-wound composite pressure vessels
Authors: Nguyen Ba Nghiep , Simmons Kevin L
Published: July 2012

A multiscale modeling approach to analyze filament-wound composite pressure vessels is developed in this article. The approach, which extends the Nguyen et al. [Prediction of the elastic-plastic stress/strain response for injection-molded long-fiber thermoplastics. J Compos Mater 2009; 43: 217–246.] model developed for discontinuous fiber composites to continuous fiber ones, spans three modeling scales. The microscale considers the unidirectional elastic fibers embedded in an elastic–plastic matrix obeying the Ramberg–Osgood relation and J2 deformation theory of plasticity. The mesoscale behavior representing the composite lamina is obtained through an incremental Mori–Tanaka [Average stress in matrix and average elastic energy of materials with misfitting inclusions. Acta Metall 1973; 21: 571–574.] type model and the Eshelby [The determination of the elastic field of an ellipsoidal inclusion and related problems. Proc R Soc Lond, Ser A 1957; 241: 376–396.] equivalent inclusion method. The implementation of the micro–meso constitutive relations in the ABAQUS® finite element package (via user subroutines) allows the analysis of a filament-wound composite pressure vessel (macroscale) to be performed. Failure of the composite lamina is predicted by a criterion that accounts for the strengths of the fibers and of the matrix as well as of their interface. The developed approach is validated in the analysis of an aluminum liner – T300 carbon/epoxy pressure vessel to predict the burst pressure. The predictions compare favorably with the numerical and experimental results by Lifshitz and Dayan [Filament-wound pressure vessel with thick metal liner. Compos Struct 1995; 32: 313–323]. The approach will be further demonstrated in the study of the effects of the lamina thickness, helical angle, and fiber–matrix material combination on the burst pressure.
Parental Characteristics, Family Structure and Occupational Attainment in Britain
Authors: Lampard Richard
Published: July 2012

This article uses multivariate logistic regression analyses of the 2005 General Household Survey to assess the impact of parents’ occupational and educational characteristics on occupational attainment in Britain, focusing specifically on the salariat. Differences in outcomes according to family structure are then examined, controlling for such parental characteristics. The results indicate that both parents’ characteristics are relevant, and that their effects interact. A smaller chance of a salariat occupation is evident for those who lived in a lone-mother family, lone-father family, or biological-mother stepfamily as a young teenager, reflecting different features of these family types, but consistently reflecting lower educational attainment. Both number of co-resident siblings and parental worklessness affect the odds of having a salariat occupation, this being relevant to family-type comparisons.
The Social Construction of Competition for Graduate Jobs: A Comparison between Great Britain and the Netherlands
Authors: Tholen Gerbrand
Published: July 2012

This article examines how Dutch and British students socially construct the positional competition for jobs within their educational and labour market contexts. The findings illustrate two contrasting approaches to employability. The competition for jobs as understood by the Dutch students is based on absolute performance, an unclear relationship between skills and the labour market, and the development of human capital in areas of experiences, skills and abilities. For the British students it is based on relative performance, ranking of candidates and the importance of signals. The study also shows that these principles are aligned to national labour market and educational contexts. These results highlight the importance of the institutional context in how the positional competition for graduate jobs is played out.
The Akedah as Governance Myth
Authors: Wachhaus Aaron
Published: July 2012

Some of our oldest and most powerful myths focus on sacrifice as a means of gaining power, strengthening relationships, and binding a community together. The oldest of these myths emphasizes blood sacrifices as the most powerful for this purpose. Our current American myths emphasize nearly the opposite: that success can be obtained without sacrifice. This article examines the implications of this fundamental shift on civil society. The author takes the Akedah—the Old Testament story of the binding of Isaac—as a central point in the evolution of the sacrifice myth. In particular, the author explores the evolution of “sacrifice” from ritual blood offering in a religious context to that of labor undertaken in a social context.
Revisiting Prison Privatization
Authors: Kim Younhee , Price Byron E.
Published: July 2012

This study examines the effects of capacity-oriented and institutional-based factors on the proliferation of prison privatization by extending the first generation of empirical research. This study found that correction expenditures, prison capacity, and regional identity are factors that significantly affect the magnitude of prison privatization, whereas political pressures, government ideology, and unionization were found not to have a significant influence on the growth of private prisons. The results imply that, once adopted, prison privatization became institutionalized over time and suggest that state governments should develop well-structured evaluation systems for private prisons to ensure and maintain effective correction management.
A response to Martel’s ‘Amo: Volu ut sis: Love, willing, and Arendt’s reluctant embrace of sovereignty’
Authors: Arnold Jeremy
Published: July 2012

In this article I respond to James Martel’s essay ‘ Amo: Volu ut sis: Love, willing, and Arendt’s reluctant embrace of sovereignty’. Martel offers us a provocative account of how Arendt might have attenuated her most severe rejections of the concept of sovereignty in light of the necessity of some version of sovereignty in modern times. However, I argue that Martel misreads Arendt, drawing inferences from Arendt’s inner/outer distinction that do not follow from Arendt’s own logic. Instead of this distinction, I claim that Arendt’s rejection of sovereignty must be understood in the context of her affirmation of natality, and that a consistent reading of Arendt reveals an unstinting rejection of sovereignty, for both good and ill.
Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor
Authors: Brown Russell W , Hughes Benjamin A , Hughes Andrew B , Sheppard A Brianna , Perna Marla K , Ragsdale W Lee , Roeding Ross L , Pond Brooks B
Published: July 2012

This study analyzed repeated methylphenidate (MPH) administration and its effects on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens of male and female adolescent rats. In Experiment 1, rats were administered intraperitoneal (ip) saline, 1, 3, or 5 mg/kg dose of MPH every second day from postnatal day (P)33–P49. Locomotor activity was analyzed for 10 min after each administration. Results revealed that the 1 mg/kg dose of MPH produced locomotor suppression, however, the 5 mg/kg dose of MPH produced locomotor sensitization and robust behavioral activation in females as compared to males. In Experiment 2, animals were administered ip saline or the 5 mg/kg dose of MPH using an identical regimen but a 30 min behavioral test was employed. Dorsal striatum and nucleus accumbens tissue was assayed for BDNF at P50. Females demonstrated sensitization to MPH and increased locomotor activation compared to males. Interestingly, females given MPH demonstrated a significant 42% decrease of striatal BDNF whereas males administered MPH demonstrated a significant 50.4% increase of striatal BDNF compared to controls. There were no effects on accumbal BDNF. This report demonstrates robust sex differences in the behavioral response, but sex-dependent changes in striatal BDNF in response to MPH in adolescence.
Effects of land use on annual runoff and soil loss in Europe and the Mediterranean
Authors: Maetens W. , Vanmaercke M. , Poesen J. , Jankauskas B. , Jankauskiene G. , Ionita I.
Published: July 2012

The largest currently compiled database of plot runoff and soil loss data in Europe and the Mediterranean was analysed to investigate effects of land use on annual soil loss (SL), annual runoff (R) and annual runoff coefficient (RC). This database comprises 227 plot-measuring sites in Europe and the Mediterranean, with SL for 1056 plots (PL) representing 7024 plot-years (PY) and R for 804 PL representing 5327 PY. Despite large data variability, continental-wide trends are observed. Construction sites have the highest mean annual RC (57%) and SL (325 Mg.ha-1.yr-1). Bare soil, vineyards and tree crops have high mean annual RC (5–10%) and SL (10–20 Mg.ha-1.yr-1). Cropland and fallow show similar mean annual RC (8.0 and 7.3%), but lower SL (6.5 and 5.8 Mg.ha-1.yr-1). Plots with (semi-)natural vegetation cover show lowest mean annual RC (<5%) and SL (<1 Mg.ha-1.yr-1). Plot length and slope gradient correlations with R and SL depend on land-use type and are not concurrent for R and SL. Most land-use types show positive correlations between annual R and SL. Plots in cold climates have higher annual RC than plots in temperate and pan-Mediterranean climates. Annual SL in the pan-Mediterranean is less than in temperate zones, due to stony or clayey soils having a low erodibility. Annual RC in the pan-Mediterranean was higher than in temperate zones. Annual R increases strongly with increasing annual precipitation (P) above 500 mm.yr-1, while annual SL was found to stabilize at P > 500 mm.yr-1. For shrubland, annual SL was found to decrease for P > 250–500 mm.yr-1, which is attributed to an accompanying increase in vegetation cover. However, no such trend was found for R. The results allow a rapid assessment of the impact of land-use changes on annual R, RC and SL, based on field-measured plot data.
Influence of sex, estrous cycle, and estrogen on intracranial dural mast cells
Authors: Boes Tanner , Levy Dan
Published: July 2012

Background: The frequency of migraine headaches is higher in women than in men and in susceptible women attacks are related to changes in ovarian hormone levels. Intracranial mast cells (MCs) are likely to have a role in migraine headache genesis, and changes in the dural MC population might influence headache susceptibility. The present study thus tested the hypothesis that sex and ovarian hormones influence the density and phenotypic makeup of dural MCs.

Methods: Histochemistry combined with quantitative analyses was used to investigate sex differences, estrous cycle and ovarian hormones on dural MC density, phenotype and degranulation level in male and female rats.

Results: Our data show that in female rats, dural MC density fluctuates during the estrous cycle and is overall higher than in males. In ovariectomized rats, estradiol, but not progesterone, promoted an increase in dural MC density. This effect was abolished by a splenectomy, suggesting estrogen-related recruitment of MCs from the spleen. Finally, our data suggest that the phenotypic make up of dural MCs, which represents the level of cellular maturity, is also governed by changes in estrogen levels.

Conclusions: Given the potential role of dural MCs in triggering headache, our data suggest that estrogen-related modulation of dural MC density and phenotypic makeup could have a role in mediating the higher frequency and severity of headaches such as migraine, in women.
Long-term monitoring of dioxins and furans near a municipal solid waste incinerator: human health risks
Authors: Vilavert Lolita , Nadal Martí , Schuhmacher Marta , Domingo José L
Published: July 2012

Since 1996, a wide surveillance programme has been developed to get overall information on the impact of a municipal solid waste incinerator (MSWI) in Tarragona (Catalonia, Spain). The concentrations of polychlorinated dibenzo- p-dioxins and dibenzofurans (PCDD/Fs) have been periodically measured in soil and vegetation samples collected at locations in the incinerator surroundings. Furthermore, air PCDD/F levels have been also monitored by using active and passive sampling devices, generating a huge amount of information regarding the environmental status of the zone. In the last survey (2009–2010), mean PCDD/F levels in vegetation, soil and air were 0.06 ng I-TEQ kg−1, 0.58 ng I-TEQ kg−1 and 10.5 fg WHO-TEQ m−3, respectively. Both soil and herbage showed a notable reduction in the PCDD/F concentrations in comparison with the baseline study, with this decrease only being significant for soils. In contrast, PCDD/F values in air remained similar during the whole assessment period. Human exposure to PCDD/Fs was evaluated under different scenarios, and the associated non-carcinogenic and carcinogenic risks were assessed. The hazard quotient was below unity in all cases, while cancer risks were under 10−6, which is lower than the maximum recommended guidelines. The current results clearly show that the MSWI of Tarragona does not produce additional health risks for the population living nearby.
Childhood Medulloblastoma
Authors: Sadighi Zsila , Vats Tribhawan , Khatua Soumen
Published: July 2012

Medulloblastoma is the most common malignant brain tumor of childhood, accounting for nearly 25% to 30% of primary central nervous system tumors in children younger than 18 years of age. Risk stratification into low and high risk categories has been based on age of clinical presentation, extent of postsurgical residual tumor, and disease dissemination. The World Health Organization (WHO) in 2007 recognized 5 histological subtypes as classic, anaplastic, large cell, desmoplastic/nodular, and medulloblastoma with extensive nodularity. Recent work with gene expression profiling along with histological classification has generated a novel combined histopathological and molecular stratification scheme into 4 subgroups (Wnt, Shh, group 3, and group 4). This could now help to identify patients who might benefit from dose escalation and de-escalation of therapy. Restratification brings optimism in treating these patients as scholars now have the ability to profile a more targeted therapy approach. This review discusses the literature regarding this new research endeavor.
The effect of shear on in vitro platelet and leukocyte material-induced activation
Authors: Chang Xiaojian , Gorbet Maud
Published: July 2012

The failure to understand the mechanisms of biomaterial-associated thrombosis prevents us from improving the blood compatibility of stents and mechanical heart valves. Blood-material interactions trigger a complex series of events and anticoagulant and anti-platelet therapies are needed to reduce the risks of thrombotic complications with most cardiovascular materials. While material interaction with platelets has been widely studied, little is currently known on material-induced leukocyte activation in the presence of shear. In vitro experiments were performed to assess the effect of flow on blood cell activation induced by medical grade metals, ST316L and TiAl6V4. Blood was circulated in flow chambers preloaded with or without metal wires at shear rates of 100, 500, and 1500 s−1. Platelet and leukocyte activation, leukocyte-platelet aggregation, and tissue factor expression on monocytes were measured by flow cytometry. Metal surfaces were characterized by scanning electron microscopy. Under physiological shear rates, no significant platelet microparticle formation was observed. However, significant CD11b up-regulation, leukocyte-platelet aggregates, and tissue factor expression were observed at 100 s−1. As shear rate increased to 1500 s−1, leukocyte activation reduced to control values. TiAl6V4-induced leukocyte activation was generally lower than that of ST316L. Adhesion significantly decreased with increasing shear rate to 1500 s−1.

In blood, increase within physiological shear rates led to a significant reduction in in vitro material-induced leukocyte activation, suggesting that difference between material biocompatibility may be better identified at low shear rates or under pathological shear conditions.