bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Release Kinetics in Hydroxy Double Salts: Effect of Host Anion Structure
Authors: Majoni Stephen , Hossenlopp Jeanne M.
Published: January 2014

Nanodimensional layered metal hydroxides such as layered double hydroxides (LDHs) and hydroxy double salts (HDSs) can undergo anion exchange reactions releasing intercalated anions. Because of this, these metal hydroxides have found applications in controlled release delivery of bioactive species such as drugs and pesticides. In this work, isomers of hydroxycinnamate were used as model compounds to systematically explore the effects of anion structure on the rate and extent of anion release in HDSs. Following intercalation and subsequent release of the isomers, it has been demonstrated that the nature and position of substituent groups on intercalated anions have profound effects on the rate and extent of release. The extent of release was correlated with the magnitude of dipole moments while the rate of reaction showed strong dependence on the extent of hydrogen bonding within the layers. The orthoisomer showed a more sustained and complete release as compared to the other isomers.
Challenges of Introducing Participant Observation to Community Health Research
Authors: Zhao Meng , Ji Yingchun
Published: January 2014

Participant observation elicits unique observation data from both an insider’s and an outsider’s perspectives. Despite the growing tendency to adopt participant observation strategies in health care research regarding health-related beliefs and types of behavior, the use of participant observation in current research is mostly limited to structured clinical settings rather than community settings. In this paper, we describe how we use participant observation in a community health research study with Chinese-born immigrant women. We document discrepancies between these women’s beliefs and types of behavior regarding health and health promotion. We further discuss the ethnical, time, and setting challenges in community health research using participant observation. Possible solutions are also discussed.
Effect of 26 Years of Intensively ManagedCarya cathayensisStands on Soil Organic Carbon and Fertility
Authors: Wu Jiasen , Huang Jianqin , Liu Dan , Li Jianwu , Zhang Jinchi , Wang Hailong
Published: January 2014

Chinese hickory (Carya cathayensis), a popular nut food tree species, is mainly distributed in southeastern China. A field study was carried out to investigate the effect of long-term intensive management on fertility of soils under aC.cathayensisforest. Results showed that after 26 years’ intensive management, the soil organic carbon (SOC) content of the A and B horizons reduced by 19% and 14%, respectively. The reduced components of SOC are mainly the alkyl C and O-alkyl C, whereas the aromatic C and carbonyl C remain unchanged. The reduction of active organic matter could result in degradation of soil fertility. The pH value of soil in the A horizon had dropped by 0.7 units on average. The concentrations of the major nutrients also showed a decreasing trend. On average the concentrations of total nitrogen (N), phosphorus (P), and potassium (K) of tested soils dropped by 21.8%, 7.6%, and 13.6%, respectively, in the A horizon. To sustain the soil fertility andC.cathayensisproduction, it is recommended that more organic fertilizers (manures) should be used together with chemical fertilizers. Lime should also be applied to reduce soil acidity.
The Concepts of Well-Posedness and Stability in Different Function Spaces for the 1D Linearized Euler Equations
Authors: Balint Stefan , Balint Agneta M.
Published: January 2014

This paper considers the stability of constant solutions to the 1D Euler equation. The idea is to investigate the effect of different function spaces on the well-posedness and stability of the null solution of the 1D linearized Euler equations. It is shown that the mathematical tools and results depend on the meaning of the concepts “perturbation,” “small perturbation,” “solution of the propagation problem,” and “small solution, that is, solution close to zero,” which are specific for each function space.
Stimulation of Neural Stem Cell Proliferation by Inhibition of Phosphodiesterase 5
Authors: Santos Ana I. , Carreira Bruno P. , Nobre Rui J. , Carvalho Caetana M. , Araújo Inês M.
Published: January 2014

The involvement of nitric oxide (NO) and cyclic GMP (cGMP) in neurogenesis has been progressively unmasked over the last decade. Phosphodiesterase 5 (PDE5) specifically degrades cGMP and is highly abundant in the mammalian brain. Inhibition of cGMP hydrolysis by blocking PDE5 is a possible strategy to enhance the first step of neurogenesis, proliferation of neural stem cells (NSC). In this work, we have studied the effect on cell proliferation of 3 inhibitors with different selectivity and potency for PDE5, T0156, sildenafil, and zaprinast, using subventricular zone-(SVZ-) derived NSC cultures. We observed that a short- (6 h) or a long-term (24 h) treatment with PDE5 inhibitors increased SVZ-derived NSC proliferation. Cell proliferation induced by PDE5 inhibitors was dependent on the activation of the mitogen-activated protein kinase (MAPK) and was abolished by inhibitors of MAPK signaling, soluble guanylyl cyclase, and protein kinase G. Moreover, sildenafil neither activated ERK1/2 nor alteredp27Kip1levels, suggesting the involvement of pathways different from those activated by T0156 or zaprinast. In agreement with the present results, PDE5 inhibitors may be an interesting therapeutic approach for enhancing the proliferation stage of adult neurogenesis.
Bernoulli Identities and Combinatoric Convolution Sums with Odd Divisor Functions
Authors: Kim Daeyeoul , Park Yoon Kyung
Published: January 2014

We study the combinatoric convolution sums involving odd divisor functions, their relations to Bernoulli numbers, and some interesting applications.
microRNA-148a Is a Prognostic oncomiR That Targets MIG6 and BIM to Regulate EGFR and Apoptosis in Glioblastoma
Authors: Kim Jungeun , Zhang Ying , Skalski Michael , Hayes Josie , Kefas Benjamin , Schiff David , Purow Benjamin , Parsons Sarah , Lawler Sean , Abounader Roger
Published: January 2014

Great interest persists in useful prognostic and therapeutic targets in glioblastoma. In this study, we report the definition of miRNA (miR)-148a as a novel prognostic oncomiR in glioblastoma. miR-148a expression was elevated in human glioblastoma specimens, cell lines, and stem cells (GSC) compared with normal human brain and astrocytes. High levels were a risk indicator for glioblastoma patient survival. Functionally, miR-148a expression increased cell growth, survival, migration, and invasion in glioblastoma cells and GSCs and promoted GSC neurosphere formation. Two direct targets of miR-148a were identified, the EGF receptor (EGFR) regulator MIG6 and the apoptosis regulator BIM, which rescue experiments showed were essential to mediate the oncogenic activity of miR-148a. By inhibiting MIG6 expression, miR-148a reduced EGFR trafficking to Rab7-expressing compartments, which includes late endosomes and lysosomes. This process coincided with reduced degradation and elevated expression and activation of EGFR. Finally, inhibition of miR-148a strongly suppressed GSC and glioblastoma xenograft growth in vivo. Taken together, our findings provide a comprehensive analysis of the prognostic value and oncogenic function of miR-148a in glioblastoma, further defining it as a potential target for glioblastoma therapy. Cancer Res; 74(5); 1541–53. ©2014 AACR.
Id2 Mediates Oligodendrocyte Precursor Cell Maturation Arrest and Is Tumorigenic in a PDGF-Rich Microenvironment
Authors: Havrda Matthew C. , Paolella Brenton R. , Ran Cong , Jering Karola S. , Wray Christina M. , Sullivan Jaclyn M. , Nailor Audrey , Hitoshi Yasuyuki , Israel Mark A.
Published: January 2014

Maturation defects occurring in adult tissue progenitor cells have the potential to contribute to tumor development; however, there is little experimental evidence implicating this cellular mechanism in the pathogenesis of solid tumors. Inhibitor of DNA-binding 2 (Id2) is a transcription factor known to regulate the proliferation and differentiation of primitive stem and progenitor cells. Id2 is derepressed in adult tissue neural stem cells (NSC) lacking the tumor suppressor Tp53 and modulates their proliferation. Constitutive expression of Id2 in differentiating NSCs resulted in maturation-resistant oligodendroglial precursor cells (OPC), a cell population implicated in the initiation of glioma. Mechanistically, Id2 overexpression was associated with inhibition of the Notch effector Hey1, a bHLH transcription factor that we here characterize as a direct transcriptional repressor of the oligodendroglial lineage determinant Olig2. Orthotopic inoculation of NSCs with enhanced Id2 expression into brains of mice engineered to express platelet-derived growth factor in the central nervous system resulted in glioma. These data implicate a mechanism of altered NSC differentiation in glioma development and characterize a novel mouse model that reflects key characteristics of the recently described proneural subtype of glioblastoma multiforme. Such findings support the emerging concept that the cellular and molecular characteristics of tumor cells are linked to the transformation of distinct subsets of adult tissue progenitors. Cancer Res; 74(6); 1822–32. ©2014 AACR.
Invasive Lobular Carcinoma Cell Lines Are Characterized by Unique Estrogen-Mediated Gene Expression Patterns and Altered Tamoxifen Response
Authors: Sikora Matthew J. , Cooper Kristine L. , Bahreini Amir , Luthra Soumya , Wang Guoying , Chandran Uma R. , Davidson Nancy E. , Dabbs David J. , Welm Alana L. , Oesterreich Steffi
Published: January 2014

Invasive lobular carcinoma (ILC) is a histologic subtype of breast cancer that is frequently associated with favorable outcomes, as approximately 90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that patients with ILC receiving adjuvant endocrine therapy may not benefit as much as patients with invasive ductal carcinoma. On the basis of these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome via gene expression microarray analyses and ER ChIP-Seq, and to examine response to endocrine therapy. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. We identified 915 genes that were uniquely E2 regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also E2 regulated in vivo in HCI-013. MM134 cells were de novo tamoxifen resistant and were induced to grow by 4-hydroxytamoxifen, as well as other antiestrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required fibroblast growth factor receptor (FGFR)-1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance. Cancer Res; 74(5); 1463–74. ©2014 AACR.
Frequent Overexpression of HMGA2 in Human Atypical Teratoid/Rhabdoid Tumor and Its Correlation with let-7a3/let-7b miRNA
Authors: Zhang Keqiang , Gao Hanlin , Wu Xiwei , Wang Jinhui , Zhou Wendi , Sun Guihua , Wang Jinghan , Wang Yafan , Mu Bing , Kim Charles , Chu Peiguo , Ho Donald M. , Ann David K. , Wong Tai-Tong , Yen Yun
Published: January 2014

Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b microRNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT.

Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1−/−) were investigated by antisense inhibition and ectopic overexpression studies.

Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = −0.34; P < 0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells.

Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT. Clin Cancer Res; 20(5); 1179–89. ©2014 AACR.
LINE-1 Hypomethylation, DNA Copy Number Alterations, and CDK6 Amplification in Esophageal Squamous Cell Carcinoma
Authors: Baba Yoshifumi , Watanabe Masayuki , Murata Asuka , Shigaki Hironobu , Miyake Keisuke , Ishimoto Takatsugu , Iwatsuki Masaaki , Iwagami Shiro , Yoshida Naoya , Oki Eiji , Sakamaki Kentaro , Nakao Mitsuyoshi , Baba Hideo
Published: January 2014

Purpose: Global DNA hypomethylation plays a crucial role in genomic instability and carcinogenesis. DNA methylation of the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level, and is attracting interest as a useful marker for predicting cancer prognosis. Our previous study using more than 200 esophageal squamous cell carcinoma (ESCC) specimens demonstrated the significant relationship between LINE-1 hypomethylation and poor prognosis. However, the mechanism by which LINE-1 hypomethylation affects aggressive tumor behavior has yet to be revealed.

Experimental Design: To examine the relationship between LINE-1 hypomethylation and DNA copy number variations, we investigated LINE-1–hypomethylated and LINE-1–hypermethylated ESCC tumors by comparative genomic hybridization array.

Results: LINE-1–hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. LINE-1 methylation levels were significantly associated with CDK6 mRNA and CDK6 protein expression levels in ESCC specimens. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression.

Conclusion: LINE-1 hypomethylation (i.e., global DNA hypomethylation) in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6. Clin Cancer Res; 20(5); 1114–24. ©2014 AACR.
Interactions of Hormone Replacement Therapy, Body Weight, and Bilateral Oophorectomy in Breast Cancer Risk
Authors: Cui Yong , Deming-Halverson Sandra L. , Beeghly-Fadiel Alicia , Lipworth Loren , Shrubsole Martha J. , Fair Alecia M. , Shu Xiao-Ou , Zheng Wei
Published: January 2014

Purpose: To examine potential modifying effects of body weight and bilateral oophorectomy on the association of hormone replacement therapy (HRT) with risk of breast cancer, overall and by subtypes according to status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) among postmenopausal women.

Experimental Design: This analysis included 2,510 postmenopausal white women recruited in the Nashville Breast Health Study, a population-based case–control study of breast cancer. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI) for associations between HRT use and risk of breast cancer overall and by subtypes, adjusted for age and education.

Results: Among women with natural menopause and body mass index (BMI) < 25 kg/m2, ever-use of HRT was associated with increased breast cancer risk (OR, 1.95; 95% CI, 1.32–2.88). Risk was elevated with duration of HRT use (P for trend = 0.002). Similar association patterns were found for ER+, ER+PR+, and luminal A cancer subtypes but not ER−, ER−PR−, and triple-negative cancer. In contrast, ever-HRT use in overweight women (BMI ≥ 25 kg/m2) showed no association with risk of breast cancer overall or by subtypes; interaction tests for modifying effect of BMI were statistically significant. Ever-HRT use was associated with decreased breast cancer risk (OR, 0.70; 95% CI, 0.38–1.31) among women with prior bilateral oophorectomy but elevated risk (OR, 1.45; 95% CI, 0.92–2.29) among those with hysterectomy without bilateral oophorectomy (P for interaction = 0.057). Similar associations were seen for virtually all breast cancer subtypes, although interaction tests were statistically significant for ER+ and luminal A only.

Conclusion: Body weight and bilateral oophorectomy modify associations between HRT use and breast cancer risk, especially the risk of hormone receptor–positive tumors. Clin Cancer Res; 20(5); 1169–78. ©2014 AACR.
Hedgehog–GLI Signaling Inhibition Suppresses Tumor Growth in Squamous Lung Cancer
Authors: Huang Lingling , Walter Vonn , Hayes D. Neil , Onaitis Mark
Published: January 2014

Purpose: Lung squamous cell carcinoma (LSCC) currently lacks effective targeted therapies. Previous studies reported overexpression of Hedgehog (HH)–GLI signaling components in LSCC. However, they addressed neither the tumor heterogeneity nor the requirement for HH–GLI signaling. Here, we investigated the role of HH–GLI signaling in LSCC, and studied the therapeutic potential of HH–GLI suppression.

Experimental Design: Gene expression datasets of two independent LSCC patient cohorts were analyzed to study the activation of HH–GLI signaling. Four human LSCC cell lines were examined for HH–GLI signaling components. Cell proliferation and apoptosis were assayed in these cells after blocking the HH–GLI pathway by lentiviral-shRNA knockdown or small-molecule inhibitors. Xenografts in immunodeficient mice were used to determine the in vivo efficacy of GLI inhibitor GANT61.

Results: In both cohorts, activation of HH–GLI signaling was significantly associated with the classical subtype of LSCC. In cell lines, genetic knockdown of Smoothened (SMO) produced minor effects on cell survival, whereas GLI2 knockdown significantly reduced proliferation and induced extensive apoptosis. Consistently, the SMO inhibitor GDC-0449 resulted in limited cytotoxicity in LSCC cells, whereas the GLI inhibitor GANT61 was very effective. Importantly, GANT61 demonstrated specific in vivo antitumor activity in xenograft models of GLI+ cell lines.

Conclusion: Our studies demonstrate an important role for GLI2 in LSCC, and suggest GLI inhibition as a novel and potent strategy to treat a subset of patients with LSCC. Clin Cancer Res; 20(6); 1566–75. ©2014 AACR.
BRAFV600E Cooperates with PI3K Signaling, Independent of AKT, to Regulate Melanoma Cell Proliferation
Authors: Silva Jillian M. , Bulman Christina , McMahon Martin
Published: January 2014

Mutationally activated BRAFV600E cooperates with PTEN silencing in the conversion of normal melanocytes to metastatic melanoma cells, but the mechanism underlying this cooperation is poorly understood. Here, the consequences of pharmacologic blockade of BRAFV600E or phosphoinositide 3-kinase (PI3K) signaling were explored using pathway-targeted inhibitors and a panel of human BRAF-mutated melanoma-derived cell lines. Blockade of BRAFV600E → MEK1/2 → ERK1/2 or class I PI3K inhibited melanoma proliferation, whereas inhibition of AKT had only modest effects, even in cells with mutated or amplified AKT. Although single-agent inhibition of either BRAFV600E or PI3K signaling elicited antiproliferative effects, combinatorial inhibition was more potent. Analysis of signaling downstream of BRAFV600E or PI3K revealed that these pathways cooperated to regulate protein synthesis through AKT-independent, mTOR complex 1 (mTORC1)-dependent effects on p70S6K, ribosomal protein S6, and 4E-BP1 phosphorylation. Moreover, inhibition of mTORC1/2 inhibited cell proliferation as profoundly as single-agent inhibition of either BRAFV600E or PI3K signaling. These data reveal a mechanism by which BRAFV600E and PI3K signaling cooperate to regulate melanoma proliferation through AKT-independent effects on protein translation. Furthermore, this study provides a potential foundation for pathway-targeted combination therapy designed to enhance the therapeutic benefit to patients with melanoma that contain combined alterations in BRAF and PI3K signaling.

Implications: PI3K, but not AKT, represent potential targets for melanoma therapy. Mol Cancer Res; 12(3); 447–63. ©2014 AACR.
A Relatively High Number of Pregnant Women in Kuwait Remain Susceptible to Rubella: A Need for an Alternative Vaccination Policy
Authors: Madi Nada , Al-Tawalah Haya , Abdul Khalik Dina , Al-Nakib Widad
Published: January 2014

Objective: To measure the prevalence of anti-rubella IgG and hepatitis B surface antigen (HBsAg) among pregnant women in Kuwait in order to assess the effectiveness of the current vaccination programs. Subjects and Methods: This retrospective study involved 4,062 pregnant women evaluated in health centers in the Hawalli Province of Kuwait. They were screened for anti-rubella IgG and HBsAg using commercially available assays. The data were obtained from medical laboratory records. Results: The mean age of the pregnant women was 29.2 ± 5.26 years (range 17-49). The rubella IgG prevalence among the pregnant women was 88.4% (n = 3,589); 276 (6.8%) of the pregnant women had no antibody to rubella, and 197 (4.8%) had rubella antibody levels ≤10 IU/ml. Therefore, 473 (11.6%) of the pregnant women were susceptible to rubella. The proportion of susceptible women increased with increasing age from 3.4 to 10.3% and from 3.4 to 6.7% among women aged <20 years and those aged ≥40 years, respectively (p = 0.016). The prevalence of HBsAg was 0.3%, and it did not vary with age. Conclusion: The prevalence of both anti-rubella IgG and HBsAg among pregnant women in Kuwait was relatively high. However, about 11.6% of pregnant women in Kuwait remain susceptible to rubella infection and hence congenital infection and fetal malformation.
Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery
Authors: Billings Frederic T. , Yu Chang , Byrne John G. , Petracek Michael R. , Pretorius Mias
Published: January 2014

Background: Intraoperative hemolysis and inflammation are associated with acute kidney injury (AKI) following cardiac surgery. Plasma-free hemoglobin induces heme oxygenase-1 (HO-1) expression. HO-1 degrades heme but increases in experimental models of AKI. This study tested the hypothesis that plasma HO-1 concentrations are associated with intraoperative hemolysis and are increased in patients that develop AKI following cardiac surgery. Methods: We measured plasma HO-1, free hemoglobin, and inflammatory markers in 74 patients undergoing cardiopulmonary bypass (CPB). AKI was defined as an increase in serum creatinine concentration of 50% or 0.3 mg/dl within 72 h of surgery. Results: Twenty-eight percent of patients developed AKI. HO-1 concentrations increased from 4.2 ± 0.2 ng/ml at baseline to 6.6 ± 0.5 ng/ml on postoperative day (POD) 1 (p < 0.001). POD1 HO-1 concentrations were 3.1 ng/ml higher (95% CI 1.1-5.1) in AKI patients, as was the change in HO-1 from baseline to POD1 (4.4 ± 1.3 ng/ml in AKI patients vs. 1.5 ± 0.3 ng/ml in no-AKI patients, p = 0.006). HO-1 concentrations remained elevated in AKI patients even after controlling for AKI risk factors and preoperative drug therapy. Peak-free hemoglobin concentrations correlated with peak HO-1 concentrations on POD1 in patients that developed AKI (p = 0.02). Duration of CPB and post-CPB IL-6 and IL-10 concentrations were also associated with increased HO-1 on POD1. Conclusion: Plasma HO-1 is increased in patients that develop AKI, and CPB duration, hemolysis, and inflammation are associated with increased HO-1 concentrations following cardiac surgery. Strategies that alter hemolysis and HO-1 expression during cardiac surgery may affect risk for AKI.
How Accurate Is the Eyeball Test?
Authors: Jain Renuka , Duval Sue , Adabag Selcuk
Published: January 2014

Background—

In the era of increasing percutaneous treatment options for heart disease, the estimation of surgical risk has become a key factor in selecting optimal treatment strategies. Surgical risk has historically been estimated by physician’s subjective assessment and more recently by statistical risk estimates.

Methods and Results—

We studied 5099 consecutive patients who underwent cardiac surgery at Minneapolis Veterans Affairs Medical Center between 1993 and 2010. Operative mortality risk was estimated statistically by the Veterans Affairs mortality risk estimate and subjectively by cardiac surgeons before surgery. Observed mortality rate was 3.3% (168 deaths) at 1 month, 7.1% (360 deaths) at 1 year, and 18.5% (942 deaths) at 5 years after surgery. Physician’s risk estimate (mean [SD], 5.6% [4.4]) and statistical risk estimate (4.3% [5.1]) had modest correlation (c-index, 0.56;
P
<0.001). Both methods modestly overestimated operative mortality risk. Statistical risk estimate was significantly better than physician’s risk estimate in separating patients who died from those who survived at 30 days (c-index, 0.78 versus 0.73;
P
=0.003), at 1 year (c-index, 0.72 versus 0.61;
P
<0.001), and at 5 years (c-index, 0.72 versus 0.64;
P
<0.001) after surgery. Physician’s risk estimate was higher than statistical risk estimate in all subgroups except high-risk patients.

Conclusions—

In patients undergoing cardiac surgery, statistical risk estimate is a better method to predict operative and long-term mortality compared with physician’s subjective risk estimate. However, both methods modestly overestimate actual operative mortality risk.
Peripheral Arterial Testing Before Lower Extremity Amputation Among Medicare Beneficiaries, 2000 to 2010
Authors: Vemulapalli Sreekanth , Greiner Melissa A. , Jones W. Schuyler , Patel Manesh R. , Hernandez Adrian F. , Curtis Lesley H.
Published: January 2014

Background—

Despite mild reductions in rates of lower extremity amputation over the past decade, few data exist on the use of arterial testing in patients before amputation.

Methods and Results—

Using Medicare claims from 2000 through 2010, we examined rates of preamputation arterial testing between 0 to 12 and 0 to 24 months before amputation. We used multivariable, modified Poisson regression models to identify patient and clinical predictors of preamputation arterial testing. The main outcome measures were rates of preamputation arterial testing. Among 17 463 patients undergoing nontraumatic amputation, 68.4% underwent some type of arterial testing. Of these patients, 47.5% underwent ankle-brachial index measurement, 38.7% duplex ultrasound, 31.1% invasive angiography, 6.7% computed tomographic angiography, and 5.6% magnetic resonance angiography. Temporal analysis revealed an increase in testing from 65.7% in 2002 to 69.2% in 2010 (
P
<0.001). The use of preamputation arterial testing varied significantly by location of amputation and was lowest for foot amputation (62.5%), followed by above-knee amputation (69.0%) and below-knee amputation (76.7%;
P
<0.001). After multivariable adjustment, older age, male sex, black race, renal disease, diabetes mellitus, known peripheral arterial disease, evaluation by a vascular specialist, and living in the East North Central region were associated with greater rates of preamputation arterial testing.

Conclusions—

Rates of evaluation for peripheral arterial disease before amputation were low, and testing varied by patient, provider, and regional characteristics.
Using Internally Developed Risk Models to Assess Heterogeneity in Treatment Effects in Clinical Trials
Authors: Burke James F. , Hayward Rodney A. , Nelson Jason P. , Kent David M.
Published: January 2014

Background—

Recent proposals suggest that risk-stratified analyses of clinical trials be routinely performed to better enable tailoring of treatment decisions to individuals. Trial data can be stratified using externally developed risk models (eg, Framingham risk score), but such models are not always available. We sought to determine whether internally developed risk models, developed directly on trial data, introduce bias compared with external models.

Methods and Results—

We simulated a large patient population with known risk factors and outcomes. Clinical trials were then simulated by repeatedly drawing from the patient population assuming a specified relative treatment effect in the experimental arm, which either did or did not vary according to a subject’s baseline risk. For each simulated trial, 2 internal risk models were developed on either the control population only (internal controls only) or the whole trial population blinded to treatment (internal whole trial). Bias was estimated for the internal models by comparing treatment effect predictions to predictions from the external model. Under all treatment assumptions, internal models introduced only modest bias compared with external models. The magnitude of these biases was slightly smaller for internal whole trial models than for internal controls only models. Internal whole trial models were also slightly less sensitive to bias introduced by overfitting and less sensitive to falsely identifying the existence of variability in treatment effect across the risk spectrum compared with internal controls only models.

Conclusions—

Appropriately developed internal models produce relatively unbiased estimates of treatment effect across the spectrum of risk. When estimating treatment effect, internally developed risk models using both treatment arms should, in general, be preferred to models developed on the control population.
Cost-Effectiveness of Optimal Use of Acute Myocardial Infarction Treatments and Impact on Coronary Heart Disease Mortality in China
Authors: Wang Miao , Moran Andrew E. , Liu Jing , Coxson Pamela G. , Heidenreich Paul A. , Gu Dongfeng , He Jiang , Goldman Lee , Zhao Dong
Published: January 2014

Background—

The cost-effectiveness of the optimal use of hospital-based acute myocardial infarction (AMI) treatments and their potential impact on coronary heart disease (CHD) mortality in China is not well known.

Methods and Results—

The effectiveness and costs of optimal use of hospital-based AMI treatments were estimated by the CHD Policy Model-China, a Markov-style computer simulation model. Changes in simulated AMI, CHD mortality, quality-adjusted life years, and total healthcare costs were the outcomes. The incremental cost-effectiveness ratio was used to assess projected cost-effectiveness. Optimal use of 4 oral drugs (aspirin, β-blockers, statins, and angiotensin-converting enzyme inhibitors) in all eligible patients with AMI or unfractionated heparin in non–ST-segment–elevation myocardial infarction was a highly cost-effective strategy (incremental cost-effectiveness ratios approximately US $3100 or less). Optimal use of reperfusion therapies in eligible patients with ST-segment–elevation myocardial infarction was moderately cost effective (incremental cost-effectiveness ratio ≤$10 700). Optimal use of clopidogrel for all eligible patients with AMI or primary percutaneous coronary intervention among high-risk patients with non–ST-segment–elevation myocardial infarction in tertiary hospitals alone was less cost effective. Use of all the selected hospital-based AMI treatment strategies together would be cost-effective and reduce the total CHD mortality rate in China by ≈9.6%.

Conclusions—

Optimal use of most standard hospital-based AMI treatment strategies, especially combined strategies, would be cost effective in China. However, because so many AMI deaths occur outside of the hospital in China, the overall impact on preventing CHD deaths was projected to be modest.
Inhibition of Transforming Growth Factor-β Attenuates Brain Injury and Neurological Deficits in a Rat Model of Germinal Matrix Hemorrhage
Authors: Manaenko Anatol , Lekic Tim , Barnhart Margaret , Hartman Richard , Zhang John H.
Published: January 2014

Background and Purpose—

Transforming growth factor-β (TGF-β) overproduction and activation of the TGF-β pathway are associated with the development of brain injury following germinal matrix hemorrhage (GMH) in premature infants. We examined the effects of GMH on the level of TGF-β1 in a novel rat collagenase-induced GMH model and determined the effect of inhibition of the TGF receptor I.

Methods—

In total, 92 seven-day old (P7) rats were used. Time-dependent effects of GMH on the level of TGF-β1 and TGF receptor I were evaluated by Western blot. A TGF receptor I inhibitor (SD208) was administered daily for 3 days, starting either 1 hour or 3 days after GMH induction. The effects of GMH and SD208 on the TGF-β pathway were evaluated by Western blot at day 3. The effects of GMH and SD208 on cognitive and motor function were also assessed. The effects of TGF receptor I inhibition by SD208 on GMH-induced brain injury and underlying molecular pathways were investigated by Western blot, immunofluorescence, and morphology studies 24 days after GMH.

Results—

GMH induced significant delay in development, caused impairment in both cognitive and motor functions, and resulted in brain atrophy in rat subjects. GMH also caused deposition of both vitronectin (an extracellular matrix protein) and glial fibrillary acidic protein in perilesion areas, associated with development of hydrocephalus. SD208 ameliorated GMH-induced developmental delay, improved cognitive and motor functions, and attenuated body weight loss. SD208 also decreased vitronectin and glial fibrillary acidic protein deposition and decreased GMH-induced brain injury.

Conclusions—

Increased level of TGF-β1 and activation of the TGF-β pathway associate with the development of brain injury after GMH. SD208 inhibits GMH-induced activation of the TGF-β pathway and leads to an improved developmental profile, partial recovery of cognitive and motor functions, and attenuation of GMH-induced brain atrophy and hydrocephalus.
Thrombelastography Detects Possible Coagulation Disturbance in Patients With Intracerebral Hemorrhage With Hematoma Enlargement
Authors: Kawano-Castillo Jorge , Ward Eric , Elliott Andrea , Wetzel Jeremy , Hassler Amanda , McDonald Mark , Parker Stephanie A. , Archeval-Lao Joancy , Tremont Chad , Cai Chunyan , Pivalizza Evan , Rahbar Mohammad H. , Grotta James C.
Published: January 2014

Background and Purpose—

Intracerebral hemorrhage (ICH) has high morbidity, and hematoma enlargement (HE) causes worse outcome. Thrombelastography (TEG) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. We used TEG to detect changes in clotting in patients with and without HE after ICH.

Methods—

This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and at 36±12 hours, and HE was defined as total volume increase >6 cc or >33%. TEG was also obtained from 57 controls.

Results—

Compared with controls, patients with ICH demonstrated faster and stronger clot formation; shorter R and delta (
P
<0.0001) at baseline; and higher MA and G (
P
<0.0001) at 36 hours; 11 patients had HE. After controlling for potential confounders, baseline K and delta were longer in HE+ compared with HE− patients, indicating that HE+ patients had slower clot formation (
P
<0.05). TEG was not different between HE+ and HE− patients at 36 hours.

Conclusions—

TEG may detect important coagulation changes in patients with ICH. Clotting may be faster and stronger in immediate response to ICH, and a less robust response may be associated with HE. These findings deserve further investigation.
Does Abnormal Circadian Blood Pressure Pattern Really Matter in Patients With Transient Ischemic Attack or Minor Stroke?
Authors: Zhang WenWen , Cadilhac Dominique A. , Churilov Leonid , Donnan Geoffrey A. , O’Callaghan Christopher , Dewey Helen M.
Published: January 2014

Background and Purpose—

Patients with stroke are more likely to have impaired autonomic nervous function and abnormal circadian blood pressure (BP) patterns. It remains unclear whether circadian BP patterns in patients with transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤3) differ from those in the normal population.

Methods—

Participants were assessed using a 24-hour ambulatory BP monitor and a short-term measurement of heart rate variability.

Results—

There were 76 patients (mean age, 67.2 years; 57.9% men; and 61.8% transient ischemic attack) and 82 controls (65.6 years; 54.9% men). A history of hypertension was more prevalent in patients (72.4%; controls 48.8%). Circadian BP patterns were distributed similarly among patients and controls, and heart rate variability was also consistent between patients and controls.

Conclusions—

In contrast to previous findings among patients with acute stroke, patients with transient ischemic attack or minor stroke had similar BP patterns and autonomic nervous system function, when compared with controls.
Taxonomy, lectotypification and distribution of Andrographis stenophylla (Acanthaceae), a little known endemic species from southern India
Authors: GNANASEKARAN GUNADAYALAN , MURTHY GARIMELLA VENKATA SURYANARAYANA
Published: January 2014

Andrographis stenophylla (Acanthaceae) is lectotypified and its taxonomy and distribution are discussed. The species is reported here as an addition to the flora of Andhra Pradesh and Kerala. Illustrations, photographs, a digital image of the selected lectotype and a distribution map are provided.
Talking Peace, Making Weapons
Authors: Brown Robert L. , Kaplow Jeffrey M.
Published: January 2014

A growing literature suggests that nuclear assistance from other countries is an important determinant of whether states pursue nuclear weapons. Existing work does not consider, however, the most widely available source of assistance—the Technical Cooperation (TC) program administered by the International Atomic Energy Agency (IAEA). IAEA assistance is an important piece of the nonproliferation regime’s central bargain: member states enjoy nuclear assistance in exchange for agreeing not to seek nuclear weapons. Using a data set of TC projects since 1972, we examine whether international nuclear assistance is associated with the pursuit of nuclear weapons. We hypothesize that some TC assistance reduces the cost of pursuing nuclear weapons, making weapons programs more likely. We find that receiving TC related to the nuclear fuel cycle is a statistically and substantively significant factor in state decisions since 1972 to seek nuclear weapons, with important implications for existing theories of nuclear proliferation.
Sequential TPF chemotherapy followed by concurrent chemoradiotherapy in locally advanced head and neck cancer – a retrospective analysis of toxicity and outcomes
Authors: Sanders IW , Haslett K , Correa P , Paterson C , James A , Rizwanullah M , Grose D
Published: January 2014

Background and aims

Phase III trials have shown that the addition of a taxane to cisplatin/5FU-based induction chemotherapy (TPF) improves response rates and overall survival in unresectable stage III/IV head and neck cancer. We sought to assess the tolerability, compliance and clinical outcomes of this treatment regime.

Methods

A retrospective study of patients treated within a single centre between September 2007 and November 2010. Toxicities were graded according to CTCAE version 3.0. Survival, distant metastasis and local control rates are expressed as percentages at two years using the Kaplan–Meier method.

Results

A total of 100 patients were identified (11% stage III, 86% stage IV) and 32% of patients were admitted as an emergency after TPF. The rate of neutropenic fever was 31%, this number fell to 9% when prophylactic G-CSF was used. In addition, 89% of patients underwent radical chemoradiation. Of these, 96% completed the full radiotherapy course. However, only 64% of patients received a minimum of two cycles of concurrent platinum chemotherapy. The two-year overall survival, metastasis free survival and local control rates were 62.6%, 88.5% and 73.3%, respectively.

Conclusions

TPF chemotherapy can be delivered safely in a non-trial cohort of patients. There is, however, a significant reduction in concurrent chemotherapy dose intensity. The long-term impact of this remains unclear.
Seizure secondary to cardiac arrythmias
Authors: Gardezi SKM , Chalmers RM , Pegge NC
Published: January 2014

Background

The relationship between seizure activity and arrhythmias is not well established. Sinus tachycardia is commonly seen post seizure. Bradyarrythmias leading to seizure activity is rarely reported in the literature thus far.

Case presentation

A 62-year-old lady presented with nocturnal seizures and was subsequently started on oral anti-convulsant with no relief of her symptoms. Further investigations led to outpatient ambulatory ECGs which showed marked sinus bradycardia prior to seizure activity and post seizure atrial fibrillation with fast ventricular rate. The patient was commenced on oral anticoagulant and beta blocker for ventricular rate control in view of atrial fibrillation. A backup dual chamber permanent pacemaker was implanted to treat the bradycardia. The patient became seizure free since the implantation of permanent pacemaker.

Conclusion

This case stresses the importance of investigating and treating cardiac arrhythmias underlying seizure activity.
Communicating Hurricane Evacuation to Tourists
Authors: Cahyanto Ignatius , Pennington-Gray Lori
Published: January 2014

The article discusses how the role of gender, residence, and past experience with hurricanes affects tourists’ voluntary evacuation in the event of hurricanes. The study examines how the aforesaid variables influence the perceived credibility of the information source and how such perceptions are translated into voluntary evacuation decisions. The findings indicate that the aforesaid variables significantly influence the perception of the credibility of the information source and information search behaviors leading to a voluntary evacuation decision. Implications of the findings are also discussed.
Transparency
Authors: Piotrowski Suzanne J.
Published: January 2014

The argument presented in this article is a relatively basic one but one that has been overlooked by students of public administration ethics. The analysis is grounded in the writing and ideas of John A. Rohr. Rohr’s body of work includes a focus on ethics and regime values. I show that transparency and ethics are two terms frequently conflated in common usage. Rohr developed the concept of regime values, which is a central component of this article. My first key point is that governmental transparency fits the definition of a regime value laid out by Rohr. Second, while transparency and ethics are frequently conflated, ethics is conceptually broader than transparency.
The World’s Not Ready for This
Authors: Martin Lauren Jade
Published: January 2014

The United States has become an ideal marketplace for those seeking selective technologies that are illegal, inaccessible, or unavailable in their own countries. Specifically, technologies such as commercial egg donation, preimplantation genetic diagnosis (PGD), and sex selection are prohibited or highly regulated in many nations, but remain legal and largely unregulated in the United States. Based on in-depth interviews with US fertility industry providers, including physicians and egg donor and surrogate brokers, this article analyzes how the ideologies of genetic determinism and consumer choice are embedded in the industry. These are transformed into competitive advantages that may appeal to foreign nationals unable to acquire the technologies, services, and reproductive materials to which they feel entitled. Regardless of providers’ particular attitudes regarding the uses of selective technologies, their overall practice reinforces intended parents’ desires to have some control over their potential children’s appearance, temperament, abilities, and behavior. Despite other nations’ laws and policies, ideologies supportive of the use of selective technologies do not, obviously, end at the US borders, and the globalization of communications, media, and transportation technologies enable their spread.
The Impact of Prison Reentry Services on Short-Term Outcomes
Authors: Lattimore Pamela K. , Visher Christy A.
Published: January 2014

Background:

Renewed interest in prisoner rehabilitation to improve postrelease outcomes occurred in the 1990s, as policy makers reacted to burgeoning prison populations with calls to facilitate community reintegration and reduce recidivism. In 2003, the Federal government funded grants to implement locally designed reentry programs. Adult programs in 12 states were studied to determine the effects of the reentry programs on multiple outcomes.

Research design:

A two-stage matching procedure was used to examine the effectiveness of 12 reentry programs for adult males. In the first stage, “intact group matching” was used to identify comparison populations that were similar to program participants. In the second stage, propensity score matching was used to adjust for remaining differences between groups. Propensity score weighted logistic regression was used to examine the impact of reentry program participation on multiple outcomes measured 3 months after release.

Subjects and data:

The study population was 1,697 adult males released from prisons in 2004–2005. Data consisted of interview data gathered 30 days prior to release and approximately 3 months following release, supplemented by administrative data from state departments of correction and the National Crime Information Center.

Results and conclusions:

Results suggest programs increased in-prison service receipt and produced modest positive outcomes across multiple domains (employment, housing, and substance use) 3 months after release. Although program participants reported fewer crimes, differences in postrelease arrest and reincarceration were not statistically significant. Incomplete implementation and service receipt by comparison group members may have resulted in insufficient statistical power to identify stronger treatment effects.
A modified cryo-maze procedure via the superior transseptal approach
Authors: Higuchi Kazuhiko
Published: January 2014

The superior transseptal approach provides excellent exposure for mitral valve reconstruction. For atrial fibrillation, cryoablation is less invasive, simpler, and safer than the Cox maze operation. Combining the superior transseptal approach and cryoablation for mitral valve procedures yields a high recovery rate from atrial fibrillation, similar to that of radiofrequency ablation. Cryoablation-related complications such as thromboembolic events or requirement for a permanent pacemaker were not observed in our consecutive series. Cryoablation is also cost-effective.