bluuebunny/crossref_metadata_2025 huggingface dataset:
Replication of Neuroblastoma SNP Association at the BARD1 Locus in African-Americans
Authors: Latorre Valeria , Diskin Sharon J. , Diamond Maura A. , Zhang Haitao , Hakonarson Hakon , Maris John M. , Devoto Marcella
Published: March 2012

Background: Neuroblastoma is an often fatal pediatric cancer more frequent in European-American than African-American children. African-American children, however, are at higher risk for the more severe form of neuroblastoma and have worse overall survival than European-American children. Genome-wide association studies (GWAS) have identified several single-nucleotide polymorphisms (SNP) associated to neuroblastoma in children of European descent. Knowledge of their association to neuroblastoma in African-American children is still lacking.

Methods: We genotyped and imputed SNPs located in three gene regions reported to be associated to neuroblastoma in children of European descent, and tested them for association in 390 African-American patients with neuroblastoma compared with 2,500 healthy, ethnically matched controls.

Results: SNPs in the BARD1 gene region show a similar pattern of association to neuroblastoma in African-American and European-American children. The more restricted extent of linkage disequilibrium in the African-American population suggests a smaller candidate region for the putative causal variants than previously reported. Limited association was observed at the other two gene regions tested, including LMO1 in 11p15 and FLJ22536 in 6p22.

Conclusions: Common BARD1 SNPs affect risk of neuroblastoma in African-Americans. The role of other SNPs associated to neuroblastoma in children of European descent could not be confirmed, possibly due to different patterns of linkage disequilibrium or limited statistical power to detect association to variants with small effect on disease risk. Extension of GWAS to populations of African descent is important to confirm their results and validity beyond the European populations and can help to refine the location of the putative causal variants. Cancer Epidemiol Biomarkers Prev; 21(4); 658–63. ©2012 AACR.
Aberrant Vimentin Methylation Is Characteristic of Upper Gastrointestinal Pathologies
Authors: Moinova Helen , Leidner Rom S. , Ravi Lakshmeswari , Lutterbaugh James , Barnholtz-Sloan Jill S. , Chen Yanwen , Chak Amitabh , Markowitz Sanford D. , Willis Joseph E.
Published: March 2012

Background: We have previously established aberrant DNA methylation of vimentin exon-1 (VIM methylation) as a common epigenetic event in colon cancer and as a biomarker for detecting colon neoplasia. We now examine vimentin methylation in neoplasia of the upper gastrointestinal tract.

Methods: Using a quantitative real-time methylation-specific PCR assay, we tested for vimentin methylation in archival specimens of esophageal and gastric neoplasia.

Results: We find that acquisition of aberrant vimentin methylation is highly common in these neoplasms, but largely absent in controls. The highest frequency of vimentin methylation was detected in lesions of the distal esophagus, including 91% of Barrett's esophagus (n = 11), 100% of high-grade dysplasia (HGD, n = 5), and 81% of esophageal adenocarcinoma (EAC, n = 26) but absent in controls (n = 9). Vimentin methylation similarly was detected in 87% of signet ring (n = 15) and 53% of intestinal type gastric cancers (n = 17). Moreover, in tests of cytology brushings vimentin methylation proved detectable in 100% of Barrett's esophagus cases (n = 7), 100% of HGD cases (n = 4), and 83% of EAC cases (n = 18) but was absent in all controls (n = 5).

Conclusions: These findings establish aberrant vimentin methylation as a highly common epigenetic alteration in neoplasia of the upper gastrointestinal tract and show that Barrett's esophagus, even without dysplasia, already contains epigenetic alterations characteristic of adenocarcinoma.

Impact: These findings suggest vimentin methylation as a biomarker of upper gastrointestinal neoplasia with potential for development as molecular cytology in esophageal screening. Cancer Epidemiol Biomarkers Prev; 21(4); 594–600. ©2012 AACR.
Prediagnostic 25-Hydroxyvitamin D,VDRandCASRPolymorphisms, and Survival in Patients with Colorectal Cancer in Western European Populations
Authors: Fedirko Veronika , Riboli Elio , Tjønneland Anne , Ferrari Pietro , Olsen Anja , Bueno-de-Mesquita H. Bas , van Duijnhoven Fränzel J.B. , Norat Teresa , Jansen Eugène H.J.M. , Dahm Christina C. , Overvad Kim , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Racine Antoine , Lukanova Annekatrin , Teucher Birgit , Boeing Heiner , Aleksandrova Krasimira , Trichopoulou Antonia , Benetou Vassiliki , Trichopoulos Dimitrios , Grioni Sara , Vineis Paolo , Panico Salvatore , Palli Domenico , Tumino Rosario , Siersema Peter D. , Peeters Petra H. , Skeie Guri , Brustad Magritt , Chirlaque Maria-Dolores , Barricarte Aurelio , Ramón Quirós Jose , Sánchez Maria José , Dorronsoro Miren , Bonet Catalina , Palmqvist Richard , Hallmans Göran , Key Timothy J. , Crowe Francesca , Khaw Kay-Tee , Wareham Nick , Romieu Isabelle , McKay James , Wark Petra A. , Romaguera Dora , Jenab Mazda
Published: March 2012

Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.

Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.

Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend = 0.04) and overall mortality (Ptrend = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.

Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC.

Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients. Cancer Epidemiol Biomarkers Prev; 21(4); 582–93. ©2012 AACR.
Postmenopausal Hormone Therapy and Colorectal Cancer Risk in Relation to Somatic KRAS Mutation Status among Older Women
Authors: Limburg Paul J. , Limsui David , Vierkant Robert A. , Tillmans Lori S. , Wang Alice H. , Lynch Charles F. , Anderson Kristin E. , French Amy J. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R.
Published: March 2012

Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)].

Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI).

Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation–negative (RR = 0.83; 95% CI, 0.66–1.06; P = 0.14) and KRAS mutation–positive (RR = 0.82; 95% CI, 0.58–1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation–negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43–0.96; P = 0.03).

Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMH therapy. These data suggest that PMH therapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits for KRAS mutation–negative than mutation-positive tumors (at least in the distal colorectum).

Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy–related CRC risk reduction. Cancer Epidemiol Biomarkers Prev; 21(4); 681–4. ©2012 AACR.
Plasticity of Surface Structures and β
2
-Adrenergic Receptor Localization in Failing Ventricular Cardiomyocytes During Recovery From Heart Failure
Authors: Lyon Alexander R. , Nikolaev Viacheslav O. , Miragoli Michele , Sikkel Markus B. , Paur Helen , Benard Ludovic , Hulot Jean-Sebastien , Kohlbrenner Erik , Hajjar Roger J. , Peters Nicholas S. , Korchev Yuri E. , Macleod Ken T. , Harding Sian E. , Gorelik Julia
Published: March 2012

Background—

Cardiomyocyte surface morphology and T-tubular structure are significantly disrupted in chronic heart failure, with important functional sequelae, including redistribution of sarcolemmal β
2
-adrenergic receptors (β
2
AR) and localized secondary messenger signaling. Plasticity of these changes in the reverse remodeled failing ventricle is unknown. We used AAV9.SERCA2a gene therapy to rescue failing rat hearts and measured z-groove index, T-tubule density, and compartmentalized β
2
AR-mediated cAMP signals, using a combined nanoscale scanning ion conductance microscopy-Förster resonance energy transfer technique.

Methods and Results—

Cardiomyocyte surface morphology, quantified by z-groove index and T-tubule density, was normalized in reverse-remodeled hearts after SERCA2a gene therapy. Recovery of sarcolemmal microstructure correlated with functional β
2
AR redistribution back into the z-groove and T-tubular network, whereas minimal cAMP responses were initiated after local β
2
AR stimulation of crest membrane, as observed in failing cardiomyocytes. Improvement of β
2
AR localization was associated with recovery of βAR-stimulated contractile responses in rescued cardiomyocytes. Retubulation was associated with reduced spatial heterogeneity of electrically stimulated calcium transients and recovery of myocardial BIN-1 and TCAP protein expression but not junctophilin-2.

Conclusions—

In summary, abnormalities of sarcolemmal structure in heart failure show plasticity with reappearance of z-grooves and T-tubules in reverse-remodeled hearts. Recovery of surface topology is necessary for normalization of β
2
AR location and signaling responses.
Morphological and Functional Adaptation of the Maternal Heart During Pregnancy
Authors: Savu Oana , Jurcuţ Ruxandra , Giuşcă Sorin , van Mieghem Tim , Gussi Ilinca , Popescu Bogdan A. , Ginghină Carmen , Rademakers Frank , Deprest Jan , Voigt Jens-Uwe
Published: March 2012

Background—

Pregnancy provides a unique model to study the adaptation of the heart in a physiological situation of transient load changes. The aim of this study was to assess the performance of the left ventricle (LV) in normal, uncomplicated pregnancies while considering the actual LV load and shape.

Methods and Results—

Serial echocardiographic examinations were performed in 51 women in each pregnancy trimester and 3 to 6 months after delivery. Data from 10 nulliparous, age-matched women were used as the control. Conventional parameters of LV function (ejection fraction) as well as myocardial deformation (strain) were interpreted, taking into consideration maternal hemodynamics and LV shape. Cardiac output increased during pregnancy because of a higher stroke volume in early pregnancy and a late increase in heart rate, whereas total vascular resistance decreased. Progressive development of eccentric hypertrophy was observed, which subsequently recovered postpartum. Sphericity index decreased from the first to the third trimester (1.92±0.17 versus 1.71±0.17) and returned postpartum to values comparable to the control. Although higher LV stroke work was noted toward the third trimester (5.9±1.1 versus 5.3±1.0 Newton meter,
P
<0.001), ejection fraction showed no significant changes. LV strain decreased significantly in late pregnancy (−19.5±2% to −17.6±1.6%,
P
<0.001) and returned to baseline values after delivery (−19.5±2%).

Conclusions—

Pregnancy is a physiological process associated with increased cardiac performance and progressive LV remodeling. These changes are not directly reflected by parameters traditionally considered to describe systolic function, such as ejection fraction and longitudinal deformation. While ejection fraction was insensitive to the functional changes, the transient decrease in longitudinal deformation becomes only plausible when considering the changes in LV geometry.
Outcomes After Coronary Stent Implantation in Patients With Metal Allergy
Authors: Romero-Brufau Santiago , Best Patricia J.M. , Holmes David R. , Mathew Verghese , Davis Mark D.P. , Sandhu Gurpreet S. , Lennon Ryan J. , Rihal Charanjit S. , Gulati Rajiv
Published: March 2012

Background—

Clinical outcomes after stent placement in patients with a history of metal allergy remain incompletely understood. We performed a single-center retrospective study to evaluate such outcomes.

Methods and Results—

Twenty-nine allergic patients who underwent coronary stent implantation were compared with a nonallergic group (n=250) matched for demographics and a propensity score for allergy to metal. Hypersensitivity to nickel was reported in 26 of 29 and chromium in 9 of 29. Patch testing performed in 11 of 29 patients was positive in all. Comparing allergy versus control subjects, there were no differences in number of segments treated (1.4±0.7 versus 1.5±0.7), stents placed (1.7±1.1 versus 1.6±0.9), and frequency of drug-eluting stent usage (52% versus 60%). In-hospital death (0% versus 0%), myocardial infarction (MI, 4% versus 3%,
P
=0.27), and 30-day death (3% versus 0%,
P
=0.53) and MI (3% versus 4%,
P
=0.71) were statistically similar. There were no differences in 4-year death (12% versus 13%), target lesion revascularization (TLR, 13 versus 17%,
P
=0.54), or death/MI/TLR (24% versus 34%,
P
=0.20). Clinically driven repeat angiography in 12 of 29 allergy patients revealed binary restenosis rates of 27% in bare metal stents and 0% in drug-eluting stents, with mean diameter in-stent restenosis of 36% and 8%, respectively. There was no change in circulating eosinophil and lymphocyte counts after stenting in the allergy group (0.19–0.20,
P
=0.67, and 1.90–1.79,
P
=0.59, respectively).

Conclusions—

A history of metal allergy was not associated with adverse early or late outcomes in this single-center study.
AMP-Activated Protein Kinase Phosphorylates Cardiac Troponin I and Alters Contractility of Murine Ventricular Myocytes
Authors: Oliveira Sandra Marisa , Zhang Yin-Hua , Solis Raquel Sancho , Isackson Henrik , Bellahcene Mohamed , Yavari Arash , Pinter Katalin , Davies Joanna K. , Ge Ying , Ashrafian Houman , Walker Jeffery W. , Carling David , Watkins Hugh , Casadei Barbara , Redwood Charles
Published: March 2012

Rationale:

AMP-activated protein kinase (AMPK) is an important regulator of energy balance and signaling in the heart. Mutations affecting the regulatory γ2 subunit have been shown to cause an essentially cardiac-restricted phenotype of hypertrophy and conduction disease, suggesting a specific role for this subunit in the heart.

Objective:

The γ isoforms are highly conserved at their C-termini but have unique N-terminal sequences, and we hypothesized that the N-terminus of γ2 may be involved in conferring substrate specificity or in determining intracellular localization.

Methods and Results:

A yeast 2-hybrid screen of a human heart cDNA library using the N-terminal 273 residues of γ2 as bait identified cardiac troponin I (cTnI) as a putative interactor. In vitro studies showed that cTnI is a good AMPK substrate and that Ser150 is the principal residue phosphorylated. Furthermore, on AMPK activation during ischemia, Ser150 is phosphorylated in whole hearts. Using phosphomimics, measurements of actomyosin ATPase in vitro and force generation in demembraneated trabeculae showed that modification at Ser150 resulted in increased Ca
2+
sensitivity of contractile regulation. Treatment of cardiomyocytes with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) resulted in increased myocyte contractility without changing the amplitude of Ca
2+
transient and prolonged relaxation despite shortening the time constant of Ca
2+
transient decay (tau). Compound C prevented the effect of AICAR on myocyte function. These results suggest that AMPK activation increases myocyte contraction and prolongs relaxation by increasing myofilament Ca
2+
sensitivity.

Conclusions:

We conclude that cTnI phosphorylation by AMPK may represent a novel mechanism of regulation of cardiac function.
Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase
Authors: Schröder Katrin , Zhang Min , Benkhoff Sebastian , Mieth Anja , Pliquett Rainer , Kosowski Judith , Kruse Christoph , Luedike Peter , Michaelis U. Ruth , Weissmann Norbert , Dimmeler Stefanie , Shah Ajay M. , Brandes Ralf P.
Published: March 2012

Rationale:

The function of Nox4, a source of vascular H
2
O
2
, is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction.

Objective:

We determined the function of Nox4 in situations of increased stress induced by ischemia or angiotensin II with global and tamoxifen-inducible Nox4
−/−
mice.

Methods and Results:

Nox4 was highly expressed in the endothelium and contributed to H
2
O
2
formation. Nox4
−/−
mice exhibited attenuated angiogenesis (femoral artery ligation) and PEG-catalase treatment in control mice had a similar effect. Tube formation in cultured Nox4
−/−
lung endothelial cells (LECs) was attenuated and restored by low concentrations of H
2
O
2,
whereas PEG-catalase attenuated tube formation in control LECs. Angiotensin II infusion was used as a model of oxidative stress. Compared to wild-type, aortas from inducible Nox4-deficient animals had development of increased inflammation, media hypertrophy, and endothelial dysfunction. Mechanistically, loss of Nox4 resulted in reduction of endothelial nitric oxide synthase expression, nitric oxide production, and heme oxygenase-1 (HO-1) expression, which was associated with apoptosis and inflammatory activation. HO-1 expression is controlled by Nrf-2. Accordingly, Nox4-deficient LECs exhibited reduced Nrf-2 protein level and deletion of Nox4 reduced Nrf-2 reporter gene activity. In vivo treatment with hemin, an inducer of HO-1, blocked the vascular hypertrophy induced by Nox4 deletion in the angiotensin II infusion model and carbon monoxide, the product of HO-1, blocked the Nox4-deletion-induced apoptosis in LECs.

Conclusion:

Endogenous Nox4 protects the vasculature during ischemic or inflammatory stress. Different from Nox1 and Nox2, this particular NADPH oxidase therefore may have a protective vascular function.
Multiple Biomarkers and Risk of Clinical and Subclinical Vascular Brain Injury
Authors: Pikula Aleksandra , Beiser Alexa S. , DeCarli Charles , Himali Jayandra J. , Debette Stephanie , Au Rhoda , Selhub Jacob , Toffler Geoffrey H. , Wang Thomas J. , Meigs James B. , Kelly-Hayes Margaret , Kase Carlos S. , Wolf Philip A. , Vasan Ramachandran S. , Seshadri Sudha
Published: March 2012

Background—

Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury.

Methods and Results—

In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function
(
homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995–1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999–2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (
P
<0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (
P
>0.05). In backward elimination analyses, higher log–B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment;
P
=0.002) and log–urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment;
P
=0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (
P
=0.037). Higher C-reactive protein (β=−0.21 per 1-SD increment;
P
=0.008), D-dimer (β=−0.18 per 1-SD increment;
P
=0.041), total homocysteine (β=−0.21 per 1-SD increment;
P
=0.005), and urinary albumin/creatinine ratio (β=−0.15 per 1-SD increment;
P
=0.042) were associated with lower total cerebral brain volume.

Conclusion—

In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification.
Mutations in Cytoplasmic Loops of the KCNQ1 Channel and the Risk of Life-Threatening Events
Authors: Barsheshet Alon , Goldenberg Ilan , O-Uchi Jin , Moss Arthur J. , Jons Christian , Shimizu Wataru , Wilde Arthur A. , McNitt Scott , Peterson Derick R. , Zareba Wojciech , Robinson Jennifer L. , Ackerman Michael J. , Cypress Michael , Gray Daniel A. , Hofman Nynke , Kanters Jorgen K. , Kaufman Elizabeth S. , Platonov Pyotr G. , Qi Ming , Towbin Jeffrey A. , Vincent G. Michael , Lopes Coeli M.
Published: March 2012

Background—

β-Adrenergic stimulation is the main trigger for cardiac events in type 1 long-QT syndrome (LQT1). We evaluated a possible association between ion channel response to β-adrenergic stimulation and clinical response to β-blocker therapy according to mutation location.

Methods and Results—

The study sample comprised 860 patients with genetically confirmed mutations in the
KCNQ1
channel. Patients were categorized into carriers of missense mutations located in the cytoplasmic loops (C loops), membrane-spanning domain, C/N terminus, and nonmissense mutations. There were 27 aborted cardiac arrest and 78 sudden cardiac death events from birth through 40 years of age. After multivariable adjustment for clinical factors, the presence of C-loop mutations was associated with the highest risk for aborted cardiac arrest or sudden cardiac death (hazard ratio versus nonmissense mutations=2.75; 95% confidence interval, 1.29–5.86;
P
=0.009). β-Blocker therapy was associated with a significantly greater reduction in the risk of aborted cardiac arrest or sudden cardiac death among patients with C-loop mutations than among all other patients (hazard ratio=0.12; 95% confidence interval, 0.02–0.73;
P
=0.02; and hazard ratio=0.82; 95% confidence interval, 0.31–2.13;
P
=0.68, respectively;
P
for interaction=0.04). Cellular expression studies showed that membrane spanning and C-loop mutations produced a similar decrease in current, but only C-loop mutations showed a pronounced reduction in channel activation in response to β-adrenergic stimulation.

Conclusions—

Patients with C-loop missense mutations in the
KCNQ1
channel exhibit a high risk for life-threatening events and derive a pronounced benefit from treatment with β-blockers. Reduced channel activation after sympathetic activation can explain the increased clinical risk and response to therapy in patients with C-loop mutations.
Late Results of Percutaneous Mitral Commissurotomy up to 20 Years
Authors: Bouleti Claire , Iung Bernard , Laouénan Cédric , Himbert Dominique , Brochet Eric , Messika-Zeitoun David , Détaint Delphine , Garbarz Eric , Cormier Bertrand , Michel Pierre-Louis , Mentré France , Vahanian Alec
Published: March 2012

Background—

Long-term follow-up after percutaneous mitral commissurotomy enables predictive factors of late results to be identified.

Methods and Results—

Late results of percutaneous mitral commissurotomy were assessed in 1024 consecutive patients. Good immediate results, defined as valve area ≥1.5 cm
2
without mitral regurgitation >2/4, were obtained in 912 patients (89%). These 912 patients were randomly split into 2 cohorts comprising 609 and 303 patients that were used to develop and validate, respectively, a scoring system predicting late functional results. The 20-year rate of good functional results (survival without cardiovascular death, mitral surgery, or repeat percutaneous mitral commissurotomy and in New York Heart Association class I or II) was 30.2±2.0%. A multivariable Cox model identified 7 predictive factors of poor late functional results: higher final mean gradient (
P
<0.0001), interaction between age and final mitral valve area (
P
<0.0001) showing that the impact of valve area decreases with age, interaction between sex and valve calcification (
P
<0.0001) showing that the impact of valve anatomy is stronger in men, and interaction between rhythm and New York Heart Association class showing an impact of New York Heart Association class only in patients in atrial fibrillation (
P
<0.0001). A 13-point score enabled 3 risk groups to be defined, corresponding to predicted good functional results of 55.1%, 29.1%, and 10.5% at 20 years in the validation cohort.

Conclusions—

Twenty years after percutaneous mitral commissurotomy in a population of patients with varied characteristics, 30% still had good functional results. Prediction of late functional results is multifactorial and strongly determined by age and the quality of immediate results. A simple validated scoring system is useful for estimating individual patient outcome.
Politicization of Science in the Public Sphere
Authors: Gauchat Gordon
Published: March 2012

This study explores time trends in public trust in science in the United States from 1974 to 2010. More precisely, I test Mooney’s (2005) claim that conservatives in the United States have become increasingly distrustful of science. Using data from the 1974 to 2010 General Social Survey, I examine group differences in trust in science and group-specific change in these attitudes over time. Results show that group differences in trust in science are largely stable over the period, except for respondents identifying as conservative. Conservatives began the period with the highest trust in science, relative to liberals and moderates, and ended the period with the lowest. The patterns for science are also unique when compared to public trust in other secular institutions. Results show enduring differences in trust in science by social class, ethnicity, gender, church attendance, and region. I explore the implications of these findings, specifically, the potential for political divisions to emerge over the cultural authority of science and the social role of experts in the formation of public policy.
Strategic Alliances for Environmental Improvements
Authors: Lin Haiying
Published: March 2012

This article articulates a conceptual framework characterizing strategic alliances for environmental improvements. Drawing on the integrative perspective of the resource-based view of the firm and institutional theory, this study examines firms’ varied motivation to form strategic alliances for environmental issues and suggests that these alliances are typically either competency- or legitimacy-oriented. The author characterizes the structural configurations of these alliance types from alliance learning, partner diversity, and governance structure dimensions. These variances in structural configurations explain why competency-oriented alliances, characterized by exploration learning, diverse partners, and nonequity structure, may facilitate firms to pursue more proactive environmental strategies. This conceptual framework is supported empirically by a sample of 74 firms that participated in 146 environmental alliances in the United States from 1991 to 2007.
Conflict in Roles
Authors: Glac Katherina , Warren Danielle E. , Chen Chao C.
Published: March 2012

This empirical study examines how group membership affects the likelihood of lies occurring in a two-person negotiation setting involving an experimental design with a repeated ultimatum bargaining. To better understand the reasoning of the negotiator in in-group and out-group bargaining exercises, the authors also examined perceptions of fairness in relation to offers for the in-group and out-group. The authors find that when negotiating, individuals tell lies of greater magnitude to out-group members than to in-group members. In both situations, the magnitude of the initial lie predicts the likelihood that a concealment lie (i.e., another lie to conceal the initial lie) will be told. The study also finds that in negotiations with in-group members, the relationship between the initial lie and the concealment lie is moderated by the negotiator’s perceptions of unfair treatment toward the in-group bargaining partner. The authors assert that concealment lies with in-group members allow the individual to appear to maintain both the roles of a self-interested negotiator and a fair group member. The authors tested three hypotheses using a natural group of 42 undergraduate students who belonged to a sports team at a large Northeastern university. Implications for stakeholder research are addressed.
Examining Administrators’ Disciplinary Philosophies
Authors: Smith Brittany N. , Hains Bryan J.
Published: March 2012

Background: In the 40th Annual Phi Delta Kappa/Gallup Poll of the Public’s Attitudes Toward the Public Schools, Americans rated student discipline as the second largest problem facing public education. This poses a substantial problem for administrators striving to employ school reform policies, address public demands, and meet the needs of contemporary students. Purpose: A review of the literature revealed a large body of research that examines disciplinary practice; however, it also showcased a literary gap regarding administrative disciplinary philosophies. Research Design: This multiple case study highlights disciplinary philosophies possessed by five secondary school administrators. Analysis includes utilizing the administrator discipline facilitation continuum, an adapted discipline continuum developed to analyze administrator disciplinary philosophies. Conclusions: The versatility of the continuum as well as implications for its use and future development are discussed.
France's Occupation Costs and the War in the East: The Contribution to the German War Economy, 1940–4
Authors: Boldorf Marcel , Scherner Jonas
Published: March 2012

This article analyses how Nazi Germany exploited France, which – from an economic point of view – was the most important occupied country during the Second World War. We can show that, in contrast to the conventional wisdom, there was no clear-cut caesura in Germany’s policy of exploiting occupied France – not in the extent of the exploitation in real terms or in the kind of policy toward occupation funds. Although the war in the East and preparations for the invasion made it necessary for Germany to reduce wasteful spending of occupation funds and combat French inflation more consistently, its occupation policy did not shift radically but gradually between mid 1942 and the end of 1943. However, it was not Albert Speer’s Armament Ministry, but other German institutions, especially the Reich Finance Ministry, which played a decisive role in this process. Without this policy Germany would not have been able to increase the French contribution to the German warfare all over Europe, especially on the Eastern front.
A Case Study of a Highly Effective, Inclusive Elementary School
Authors: McLeskey James , Waldron Nancy L. , Redd Lacy
Published: March 2012

Current federal legislation holds schools accountable for ensuring that all students, including those with disabilities, make adequate yearly progress on academic achievement measures, while also including students with disabilities in general education settings whenever possible. Schools are thus expected to be both excellent and equitable in addressing the needs of all students. Evidence reveals that only a limited number of schools have been successful in meeting these sometimes competing demands for excellence and equity. This investigation addressed these issues by conducting a case study of a highly effective, inclusive elementary school. The results reveal several key practices that were important contributors to meeting the needs of all students in this school.
A reply to Theo Hobson
Authors: Biggar Nigel
Published: March 2012

Theo Hobson’s argument that there are cogent theological objections to the establishment of the Church of England is not persuasive. He concedes that the current form of establishment is liberal, but implies that this renders the Church harmless in the sense of being deferential and ineffectual. However, this does not square either with the fact of recent archiepiscopal criticism of governments or with the Church’s faithful presence in the poorest communities in the land. He then implies that establishment compromises the Church by associating it with state coercion, and yet he has already agreed that establishment is no longer coercive. He prefers the US Constitution’s formal separation of church and state, maybe because it seems to foster a level of religious vitality that is lacking in Europe. Upon critical scrutiny, however, ‘religious vitality’ is not all that it is cracked up to be. Finally, he implies that establishment is against the Spirit of Inexorable Historical Development. But surely Christians should keep their nerve and discern the spirits, and not merely defer to modern fashion.
Waddling geese in the pulpit: Kierkegaard’s hermeneutics and preaching
Authors: Edwards Aaron
Published: March 2012

This article shall outline the significance of Kierkegaard’s method of Bible reading for preaching. The key concepts in Kierkegaard’s hermeneutics (De-Familiarization, Appropriation and Consequentiality) will be applied to his condemnation of pulpit hypocrisy in nineteenth-century Denmark. This is best illustrated in his humorous parable, ‘The Tame Geese’. Kierkegaard’s critique of preaching will then be compared with Fred B. Craddock’s ‘New Homiletic’. Though superficially similar, it will be shown that Kierkegaard still upholds the authority of the preacher in a way that diverges from many postmodern misinterpretations of his work. In the light of contemporary critiques of preaching, this reflection will emphasize how Kierkegaard’s hermeneutics might be helpful in shaping a renewed approach to proclamation that catalyses genuine transformation in its hearers, beginning with the preacher’s personal engagement with the text.
The game of the stone: A sermon on 1 Peter 2.1–8
Authors: Pickstock C. J. C.
Published: March 2012

This sermon addresses the question of the bodily senses and how they are related to one another, in connection with a eucharistic interpretation of 1 Peter 2.1–8, and an analysis of G. M. Hopkins’s sonnet, ‘As kingfishers catch fire’. These discussions are related to the tradition of the spiritual senses and to a reappraisal of presence and absence. A link is made between concrete presence and particularity, on the one hand, and participation, on the other. Real presence is aligned with a perfect virtuality, and immediacy is seen as paradoxically borrowed; it always arrives from elsewhere, and yet this affirms rather than compromises its specificity. In this way, that which might be ‘stone-like’ and visible cannot be entirely commanded, and yet its visibility and lapidary quiddity, or thingness, is in no way derogated.
Assessing the Temporal and Regional Differences in the Relationships between Infant and Child Mortality and Urban Slum Prevalence in Less Developed Countries, 1990–2005
Authors: Jorgenson Andrew , Rice James , Clark Brett
Published: March 2012

Drawing from various bodies of social scientific literature and research, the authors assess the extent to which infant and child mortality rates in less developed countries are impacted by the percentage of domestic populations living in urban slum conditions. Results of two-way fixed effects panel model estimates of 80 less developed countries from 1990 to 2005 indicate that growth in the percentage of populations living in urban slum conditions positively affects both forms of mortality rate. The effects, moreover, are much more pronounced for African countries than for less developed countries in Latin America and Asia and moderately larger for the Asian nations than those in Latin America. Additional findings suggest that the magnitude of the effect of urban slum prevalence on infant and child mortality increased through time for the African countries, but not for the Latin American and Asian countries in the study.
Non-linear proportional and rate feedback design for highly non-linear systems
Authors: Nassirharand Amir
Published: March 2012

A new procedure for the design of non-linear proportional and rate feedback controllers based on a previously proposed concept is developed. The procedure is to obtain the sinusoidal-input describing function models of the system, followed by determination of the amplitude-dependent rate feedback gains. Then, this amplitude-dependent gain function is inverted to obtain the non-linear function describing a non-linear rate feedback gain. Then, the amplitude-dependent proportional gains that desensitize the overall open-loop system are determined via optimization. Finally, the obtained amplitude-dependent proportional gains are inverted to obtain the actual non-linear function describing the required non-linear behaviour of the proportional gain. Bounded-input–bounded-output stability is demonstrated by successful generation of the closed-loop describing function models, and the procedure is applied to a servo problem; the results are compared with four other non-linear controller design procedures that were reported in the open literature.
From reminiscing to reading: Home contributions to children’s developing language and literacy in low-income families
Authors: Sparks Alison , Reese Elaine
Published: March 2012

In this study, the relations among a range of literacy-related home practices and children’s acquisition of language and literacy at the outset of preschool are examined in a sample of linguistically diverse children from low-income families in the United States. Specifically, the study focuses on sources of variation found in mother–child conversations while reminiscing and book sharing, in frequency of book reading, in parent use of strategies to teach print skills, and in the child’s interest in shared book reading. Mothers’ elaborative forms of talk during reminiscing about behavior-related events were linked to children’s semantic and print knowledge. Child interest in storybook reading was related to their emerging literacy skills but not to language.
Obesity Is Not Associated With Increased Mortality and Morbidity in Critically Ill Children
Authors: Goh Vi Lier , Wakeham Martin K. , Brazauskas Ruta , Mikhailov Theresa A. , Goday Praveen S.
Published: March 2012

Aim: To evaluate the effect of obesity on mortality, length of mechanical ventilation, and length of stay (LOS) in critically ill children. Methods: Retrospective cohort study in 2‐ to 18‐year‐olds, admitted to the pediatric intensive care unit (PICU) at the Children's Hospital of Wisconsin from 2005–2009 who required invasive ventilation. Weight z score was used to categorize patients as normal (–1.89 to 1.04), overweight (1.05–1.65), obese (1.66–2.33), and severely obese (>2.33). Underweight patients were excluded. Age, gender, admission type, Pediatric Index of Mortality 2 score, operative status, trauma status, admission Pediatric Outcome Performance Category, and diagnosis categories were also collected. The outcomes were mortality, total ventilator days, and PICU LOS. Univariate analysis was used to compare the groups, and multivariate logistic regression was used to compare mortality. Total ventilation days and LOS were modeled with linear regression. Results: In total, 1030 patients were included in the study, with 753 normal weight, 137 overweight, 76 obese, and 64 severely obese. The risk‐adjusted mortality rates in overweight (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.62–1.82), obese (OR, 0.68; 95% CI, 0.31–1.48), and severely obese patients (OR, 1.02; 95% CI, 0.45–2.34) were not significantly different compared with the normal‐weight group. Total ventilation days (P = .9628) and PICU LOS (P = .8431) were not significantly different between the groups after adjusting for risk factors. Conclusion: Critically ill overweight, obese, and severely obese children who require invasive mechanical ventilation have similar mortality, length of stay in the PICU, and ventilator days as compared with normal‐weight children.
Quantifying disturbance rejection of SLIP-like running systems
Authors: Miller Bruce , Schmitt John , Clark Jonathan E
Published: March 2012

The speed and maneuverability at which legged animals can travel across rough and cluttered landscapes has provided inspiration for the development of legged robots with similar capabilities. Researchers have developed a number of robots that can run over rough terrain, but there is currently no universally accepted measure for stability in an unstructured environment. This paper considers the effectiveness of a number of stability metrics in predicting the disturbance-rejection behavior of three spring-loaded inverted pendulum (SLIP)-like systems ranging from simple reduced-order models to a one-legged mechanical hopping robot. We show that the gait stability norm utilizing leg-centric indicators and a two-step decay ratio utilizing body-centric indicators provide the best correlation between step response behavior and how the systems perform when running over unknown, uneven terrain. By providing a cross-platform stability comparison, this paper facilitates the development and evaluation of robots and control schemes, such as the active energy removal approach utilized in this paper, that aim to improve the stability of running systems.
Government Reform in China
Authors: Xue Lan , Liou Kuotsai Tom
Published: March 2012

This article examines recent government reforms in China to identify changes and lessons of the Chinese reform experience. The article provides a review of major government reform concepts and analyzes eight Chinese reform cases in four areas of government: personnel, structure, strategy, and process. These reforms have expanded the objectives and scopes of the past administrative reforms to include new governance concepts of promoting managerial competency, organizational capacity, accountability and transparency, and citizen participation. The reforms have not only reported positive lessons of local innovation and international connection but have also identified limitations and concerns about social and political stability. Implications about reform findings and challenges are provided for future studies of Chinese government reforms.
Development of the Civil Servants’ Performance Appraisal System in China
Authors: Liu Xin , Dong Keyong
Published: March 2012

The performance appraisal system for civil servants in China was developed following the establishment of the national civil servants system in 1994. Since the Civil Servant Law of the People’s Republic of China was issued, the system has been rectified twice to clarify some technical issues. Although much progress has been made since 1994, the current system is far from successful in practical operation. To improve its implementation among government agencies, the Chinese performance appraisal system needs to address some challenging issues, including the following: better connection of the performance appraisal system with other human resource management (HRM) systems, consideration of the performance budget system, and improvement of appraisal technical activities.
Surface-functionalized diatom microcapsules for drug delivery of water-insoluble drugs
Authors: Aw Moom Sinn , Bariana Manpreet , Yu Yang , Addai-Mensah Jonas , Losic Dusan
Published: March 2012

Naturally available and biocompatible materials are potential substitutes for synthetic mesoporous materials as suitable drug carriers for the development of cost-effective drug delivery systems. This work investigates the application of a porous silica material derived from diatoms, also known as diatomaceous earth. The aim is to explore the surface functionalization of diatom microcapsules and their impact on the drug loading and release characteristics of water-insoluble drugs. Indomethacin was used as the model for poorly soluble drug. The surface modification on diatoms was performed with two organosilanes; 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine and phosphonic acids (2-carboxyethyl-phosphonic acid and 16-phosphono-hexadecanoic acid) providing organic surface hydrophilic and hydrophobic properties. Extensive characterizations using scanning electron microscopy, X-ray photoelectron spectroscopy and differential scanning calorimetry was performed to confirm covalent grafting of monolayer aminosilane and phosphonic acid on the diatom surfaces. Differences in loading capacity of diatoms (15–24%) and release time (6–15 days) were observed which is due to the presence of different functional groups on the surface. It was found that 2-carboxyethyl-phosphonic acid, 3-aminopropyltriethoxy silane and N-(3-(trimethoxysilyl) propyl) ethylene diamine render diatom surfaces hydrophilic, due to polar carboxyl functional group (COOH) and active amine species (NH and NH2) that favor drug adsorption; better encapsulation efficiency and prolonged release of drugs, over the hydrophobic surface created by 16-phosphono-hexadecanoic acid. This work demonstrates diatom porous silica as a promising drug carrier, with possibility to further improve their performances by tailoring their surface functionalities to achieve the required drug loading and release characteristics for different therapeutic conditions.