bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Control of Nuclear Calcium Signaling in Cardiac Myocytes by Perinuclear Microdomains of Sarcolemmal Insulin-Like Growth Factor 1 Receptors
Authors: Ibarra Cristian , Vicencio Jose M. , Estrada Manuel , Lin Yingbo , Rocco Paola , Rebellato Paola , Munoz Juan P. , Garcia-Prieto Jaime , Quest Andrew F.G. , Chiong Mario , Davidson Sean M. , Bulatovic Ivana , Grinnemo Karl-Henrik , Larsson Olle , Szabadkai Gyorgy , Uhlén Per , Jaimovich Enrique , Lavandero Sergio
Published: November 2012

Rationale:

The ability of a cell to independently regulate nuclear and cytosolic Ca
2+
signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca
2+
signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca
2+
signals locally has not been explored.

Objective:

To study the role of perinuclear sarcolemma in selective nuclear Ca
2+
signaling.

Methods and Results:

We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca
2+
signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca
2+
signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca
2+
release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca
2+
buffers—parvalbumin—with cytosolic or nuclear localization demonstrated that the nuclear Ca
2+
handling system is physically and functionally segregated from the cytosolic Ca
2+
signaling machinery.

Conclusions:

These data reveal the existence of an inositol 1,4,5-trisphosphate–dependent nuclear Ca
2+
toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca
2+
signaling in response to an extracellular ligand.
Rhythm Versus Rate Control Therapy and Subsequent Stroke or Transient Ischemic Attack in Patients With Atrial Fibrillation
Authors: Tsadok Meytal Avgil , Jackevicius Cynthia A. , Essebag Vidal , Eisenberg Mark J. , Rahme Elham , Humphries Karin H. , Tu Jack V. , Behlouli Hassan , Pilote Louise
Published: November 2012

Background—

Stroke is a debilitating condition with an increased risk in patients with atrial fibrillation. Although data from clinical trials suggest that both rate and rhythm control are acceptable approaches with comparable rates of mortality in the short term, it is unclear whether stroke rates differ between patients who filled prescriptions for rhythm or rate control therapy.

Methods and Results—

We conducted a population-based observational study of Quebec patients ≥65 years with a diagnosis of atrial fibrillation during the period 1999 to 2007 with the use of linked administrative data from hospital discharge and prescription drug claims databases. We compared rates of stroke or transient ischemic attack (TIA) among patients using rhythm (class Ia, Ic, and III antiarrhythmics), versus rate control (β-blockers, calcium channel blockers, and digoxin) treatment strategies (either current or new users). The cohort consisted of 16 325 patients who filled a prescription for rhythm control therapy (with or without rate control therapy) and 41 193 patients who filled a prescription for rate control therapy, with a mean follow-up of 2.8 years (maximum 8.2 years). A lower proportion of patients on rhythm control therapy than on rate control therapy had a CHADS
2
(congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or TIA) score of ≥2 (58.1% versus 67.0%,
P
<0.001). Treatment with any antithrombotic drug was comparable in the 2 groups (76.8% in rhythm control versus 77.8% in rate control group). Crude stroke/TIA incidence rate was lower in patients treated with rhythm control in comparison with rate control therapy (1.74 versus 2.49, per 100 person-years,
P
<0.001). This association was more marked in patients in the moderate- and high-risk groups for stroke according to the CHADS
2
risk score. In multivariable Cox regression analysis, rhythm control therapy was associated with a lower risk of stroke/TIA in comparison with rate control therapy (adjusted hazard ratio, 0.80; 95% confidence interval, 0.74, 0.87). The lower stroke/TIA rate was confirmed in a propensity score–matched cohort.

Conclusions—

In comparison with rate control therapy, the use of rhythm control therapy was associated with lower rates of stroke/TIA among patients with atrial fibrillation, in particular, among those with moderate and high risk of stroke.
GRK2-Mediated Inhibition of Adrenergic and Dopaminergic Signaling in Right Ventricular Hypertrophy
Authors: Piao Lin , Fang Yong-Hu , Parikh Kishan S. , Ryan John J. , D'Souza Karen M. , Theccanat Tiju , Toth Peter T. , Pogoriler Jennifer , Paul Jonathan , Blaxall Burns C. , Akhter Shahab A. , Archer Stephen L.
Published: November 2012

Background—

The cause and consequences of impaired adrenergic signaling in right ventricular failure/hypertrophy (RVH) are poorly understood. We hypothesized that G protein–coupled receptor kinase-2 (GRK2)–mediated uncoupling of β-adrenergic receptor signaling impairs inotropic reserve. The implications of right ventricular (RV) adrenergic remodeling for inotrope selection and the therapeutic benefit of interrupting Gβγ–GRK2 interaction, using gallein, were tested.

Methods and Results—

Chamber-specificity and cellular localization of adrenergic remodeling were compared in rodent RVH associated with pulmonary arterial hypertension (PAH-RVH; SU5416+chronic-hypoxia or Monocrotaline) versus pulmonary artery banding–induced RVH (PAB-RVH). Results were corroborated in RV arrays from 10 PAH patients versus controls. Inotropic reserve was assessed in RV- and left ventricular–Langendorff models and in vivo. Gallein therapy (1.8 mg/kg/day ×2-weeks) was assessed. Despite similar RVH, cardiac output (58.3±4.9 versus 82.9±4.8 mL/min;
P
<0.001) and treadmill distance (41.5±11.6 versus 244.1±12.4 m;
P
<0.001) were lower in PAH-RVH versus PAB-RVH. In PAH-RVH versus PAB-RVH there was greater downregulation of β1-, α1- and dopamine-1 receptors, more left ventricular involvement, and greater impairment of RV contractile reserve. RV GRK2 activity increased in parallel with a reduction in both adrenergic receptor expression and inotrope-stimulated cAMP levels (
P
<0.01). β1-receptor downregulation also occurred in human PAH-RVH. Dobutamine was superior to dopamine as an RV inotrope, both ex vivo and in vivo.

Conclusions—

GRK2-mediated desensitization-downregulation of adrenergic and dopaminergic receptors impairs inotropic reserve in PAH-RVH. Acute inotropic support in RVH is best accomplished by dobutamine, reflecting its better coupling to adenylyl cyclase and the reliance of dopamine on dopamine-1–receptor signaling, which is impaired in RVH. Inhibiting Gβγ–GRK2 interactions has therapeutic benefit in RVH.
Prognosis of Individuals With Asymptomatic Left Ventricular Systolic Dysfunction in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Yeboah Joseph , Rodriguez Carlos J. , Stacey Brandon , Lima Joao A. , Liu Songtao , Carr J. Jeffrey , Hundley W. Gregory , Herrington David M.
Published: November 2012

Background—

Limited data exist on the prevalence, associations, and prognosis of individuals with asymptomatic left ventricular systolic dysfunction (ALVSD), especially in populations without previous clinical cardiovascular disease (CVD).

Methods and Results—

Kaplan-Meier and Cox proportional hazard analyses were used to assess the association between ALVSD, defined as left ventricular ejection fraction <50%, and adjudicated incident congestive heart failure (CHF), all-cause mortality, and CVD events. Of 5004 participants, 112 participants had CHF, 321 had a CVD event, and 278 died after 9 years of follow-up. The overall prevalence of ALVSD was 1.7%, with a higher prevalence in blacks (2.6%). ALVSD had a worse cardiovascular risk profile and was also associated with increased risk in unadjusted and adjusted models for incident CHF (HR [hazard ratio] [95% CI {confidence interval}]: 12.0 [7.04–20.3],
P
<0.0001 and 8.69 [4.89–15.45],
P
<0.001 respectively), CVD (HR [95% CI]: 3.32 [1.98–5.58],
P
<0.001 and 2.21 [1.30–3.73],
P
=0.003 respectively), and all-cause mortality (HR [95% CI]: 3.47 [2.03–5.94],
P
<0.0001 and 2.00 [1.13–3.54],
P
=0.017, respectively). A 10% decrement in left ventricular ejection fraction at baseline was associated with an increase in risk in unadjusted and adjusted models for clinical CHF (HR [95% CI]: 2.17 [1.82–2.63],
P
<0.0001 and 2.13 [1.73–2.51],
P
<0.001, respectively) and all-cause mortality (HR [95% CI]: 1.22 [1.05–1.41],
P
=0.009 and 1.17 [1.00–1.36],
P
=0.047, respectively). Among the subset of participants with ALVSD, the left ventricular mass index was particularly informative about risk for incident CHF (c-index=0.74).

Conclusions—

ALVSD is uncommon in individuals without previous clinical CVD, but it is associated with high risk for CHF, CVD, and all-cause mortality. The left ventricular mass index had good discrimination for incident CHF in Multi-Ethnic Study of Atherosclerosis (MESA) participants with ALVSD.
Fetal Heart Rate Predictors of Long QT Syndrome
Authors: Mitchell Jason L. , Cuneo Bettina F. , Etheridge Susan P. , Horigome Hitoshi , Weng Hsin-Yi , Benson D. Woodrow
Published: November 2012

Background—

Fetal long QT syndrome (LQTS) is associated with complex arrhythmias including torsades de pointes and 2° atrioventricular block. Sinus bradycardia has also been associated with fetal LQTS, but little is known of this rhythm manifestation. Our purpose was to characterize the fetal heart rate (FHR)/gestational age (GA) profile of fetal LQTS.

Methods and Results—

We ascertained fetal LQTS subjects by family history (Group 1) or fetal arrhythmia referral (Group 2). We compared FHR in LQTS subjects versus normal fetuses. To identify FHR predictors of LQTS, we calculated a bradycardia index as % of LQTS FHR recordings either ≤110 beats per minute (obstetric standard) or ≤3
rd
percentile for GA. Among 42 LQTS subjects, 26 were in Group 1 and 16 in Group 2. There were 536 normal fetuses. The bradycardia index was only 15% for FHR ≤110 beats per minute, but 66% for FHR ≤3rd percentile for GA. Ten fetuses with complex arrhythmias also had severe and sustained sinus bradycardia throughout gestation. Identifying a fetal proband in Group 2 resulted in LQTS diagnosis in 9 unsuspected members of 6 families.

Conclusions—

FHR varies by GA in both normal and LQTS fetuses. Postnatal evaluation of neonates with FHR ≤3
rd
percentile for GA may improve ascertainment of LQTS in fetuses, neonates, and undiagnosed family members.
Secondary Intracerebral Hemorrhage Due to Early Initiation of Oral Anticoagulation After Ischemic Stroke
Authors: Gliem Michael , Hermsen Derik , van Rooijen Nico , Hartung Hans-Peter , Jander Sebastian
Published: November 2012

Background and Purpose—

The uncertain risk of secondary intracerebral hemorrhage (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC) early after ischemic cardioembolic stroke. The goal of this experimental study was to determine the risk of sICH depending on the timing of OAC initiation relative to stroke onset and to address the role of hematogenous macrophages for repair processes preventing OAC-associated sICH.

Methods—

C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Subgroups were treated with either the vitamin K antagonist (VKA) phenprocoumon or the direct thrombin inhibitor dabigatran etexilate. Hematogenous macrophages were depleted using intraperitoneal injections of clodronate-filled liposomes.

Results—

Time to therapeutic OAC was 48 hours with VKA and 0.5 hours with dabigatran etexilate treatment. In VKA-treated mice, the risk of sICH was high if effective OAC was already present at stroke onset or achieved within 48 hours after ischemia. With more delayed OAC, the risk of sICH rapidly decreased. Compared with VKA treatment, effective anticoagulation with dabigatran etexilate was associated with a significantly reduced extent of sICH, either if present at stroke onset or if achieved 48 hours later. Partial depletion of macrophages greatly increased the extent of OAC-associated sICH in the subacute stage of 3 to 4 days after ischemia.

Conclusions—

Our findings suggest that repair mechanisms involving hematogenous macrophages rapidly decrease the risk of OAC-associated sICH in the first days after ischemic stroke. The lower risk of sICH under dabigatran etexilate compared with VKA treatment may facilitate early initiation of OAC after cardioembolic stroke.
A Polarized Environment
Authors: Coffey Daniel J. , Joseph Patricia Hallam
Published: November 2012

Political polarization is often analyzed at the mass level through examination of attitudinal differences, but little attention is devoted to how polarization might be manifested through differences in individual behavior, especially in areas that do not appear to be explicitly political in nature. Political polarization, however, may extend to differences in lifestyles among individuals, especially differences in prosocial environmental behavior. This could be especially true for behaviors that are perceived as markers of political attitudes. In an examination of self-reported recycling and conservation behavior, we find that controlling for a range of alternative explanations for why individuals engage in pro-environmental behavior, partisan and ideological dispositions are among the most robust causes of such behavior. We demonstrate that these behavioral differences are exacerbated by attention to political news. The findings indicate that the effects of polarization extend beyond political attitudes into social and economic choices.
Pharmacotherapy of obsessive-compulsive disorder: Evidence-based treatment and beyond
Authors: Fineberg Naomi A , Reghunandanan Samar , Brown Angus , Pampaloni Ilenia
Published: November 2012

Background:

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with a significant degree of functional disability and poor quality of life. Pharmacotherapy may have a substantial impact on the course and outcome of OCD.

Method:

We review the evidence supporting available strategies for the pharmacological treatment of OCD.

Results:

Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacological treatment of choice and are associated with improved health-related quality of life. Discontinuation is associated with relapse and loss of quality of life, implying treatment should continue long-term. A substantial minority of patients who fail to respond to SSRI may benefit from dose elevation or adjunctive antipsychotics, though long-term trials validating the effectiveness and tolerability of these strategies are relatively lacking.

Conclusion:

The pharmacological evidence-base for the treatment of OCD is becoming increasingly robust. Treatment with SSRIs and clomipramine remains uncontroversial and improvements are sustained over time. Newer compounds targeting serotonin receptor subtypes and other neurotransmitter systems are undergoing evaluation.
Complementary Relationships Between Corporate Philanthropy and Corporate Political Activity
Authors: Hadani Michael , Coombes Susan
Published: November 2012

Although an important feature of firms’ corporate social responsibility (CSR), the strategic pressures behind firms’ corporate philanthropy (CP) are not well researched or understood. This research note argues that firms’ CP and firms’ corporate political activity (CPA) may share common strategic antecedents; forces in firms’ political environment may shape both CP and CPA. Using S&P 500 data in a longitudinal analysis (1997-2004), the authors find evidence suggesting that industry-level political uncertainty increases firm propensity for engaging in both CP and CPA, above and beyond the propensity to engage in either as a stand-alone strategy. The authors use this preliminary evidence to explore political marketplace contingencies for the relationship between CP and CPA. CSR literature indicates that CP can benefit firms by creating and enhancing their relational wealth and institutional legitimacy. Such benefits may also serve firm interactions with government policy makers—a dynamic largely ignored until recently. The authors’ findings may indicate that, due to its institutional signaling ability and impact on firms’ reputations, CP may allow firms to differentiate themselves or stand out from others when faced with political uncertainty, and that these outcomes should be considered when firms engage in CP.
A Test of Labor Union Social Responsibility
Authors: Dawkins Cedric E.
Published: November 2012

Social responsibility is addressed to corporations, but can also be applied to other powerful organizations. This study tests the impact of labor union social responsibility on key measures of labor union attachment. After developing a scale of labor union social responsibility, craft union apprentice workers were surveyed and their responses analyzed with structural equation modeling. Labor union social responsibility was directly and positively related to union commitment and job satisfaction. Union commitment and job satisfaction fully mediated the negative relationship between labor union social responsibility and propensity to withdraw from the union, and the positive relationship between labor union social responsibility and union participation. The results suggest that labor union social responsibility can enhance union attachment and inform union strategy.
Coaching With Compassion
Authors: Boyatzis Richard E. , Smith Melvin L. , Beveridge ‘Alim J.
Published: November 2012

Compassion involves noticing another’s need, empathizing, and acting to enhance their well-being. In response to another’s pain, the motivation is to increase hedonic well-being or the absence of pain. In response to another’s desire to grow, the motivation is to increase eudaimonic well-being or helping them develop. We argue that compassion includes both. Our expanded view suggests that coaching with compassion will lead to desired change, enhanced health, and well-being. We propose a model saying coaching with compassion invokes a psychophysiological state that enables a person to be open to new possibilities and learning. In contrast, coaching for compliance (i.e., toward how the coach or the organization believe the person should act) and deficiency-based coaching invoke the opposite state—resulting in a person being defensive, reducing cognitive functioning. We theorize how coaching with compassion can enhance adaptability of the organization through creating norms and relationships of caring and development.
Self-Control and Substance Use Among College Students
Authors: Ford Jason A. , Blumenstein Lindsey
Published: November 2012

Gottfredson and Hirschi’s self-control theory has generated considerable academic interest and become one of the most influential theories of the past 20 years. The current study seeks to confirm and extend this line of research by examining the generality of self-control across several forms of substance use: binge drinking, marijuana use, prescription drug misuse, and other illicit drug use. Data were collected from a sample of more than 1,000 undergraduate students attending a public university in the United States. Findings indicate that students with low self-control were at greater risk for reporting binge drinking, marijuana use, and prescription drug misuse. Further analysis indicates that the influence of self-control on substance use is moderated by opportunity and peer influence. That is, self-control was significantly correlated to binge drinking and marijuana use when students reported greater opportunity to use and also when they reported substance use by their friends.
Longitudinal Relationships Between Self-Management Skills and Substance Use in an Urban Sample of Predominantly Minority Adolescents
Authors: Lowe Sarah R. , Acevedo Bianca P. , Griffin Kenneth W. , Botvin Gilbert J.
Published: November 2012

We explored changes in self-management skills and substance use from 7th to 11th grade in a multiwave study of predominantly minority adolescents ( N = 1,756). Using latent growth curve analysis, we found that substance use significantly increased, whereas self-management skills significantly decreased. In a parallel process model, we found that participants who reported higher self-management skills in the 7th grade had smaller increases in substance use. Participants who had larger decreases in self-management skills tended to have greater increases in substance use. We also explored the influence of grades and gender and found that (a) participants with higher grades at baseline had lower initial substance use, higher initial self-management skills, and smaller increases in substance use, and (b) male participants had greater increases in substance use. These results suggest that the provision of self-management skills may be an effective strategy for preventing substance-use initiation and escalation during adolescence.
Differentiating Literacy Growth of ELL Students With LD From Other High-Risk Subgroups and General Education Peers
Authors: Solari Emily J. , Petscher Yaacov , Folsom Jessica Sidler
Published: November 2012

The authors used a large data set ( N = 1,011,549) to examine literacy growth over a single school year comparing general education (GenEd) students to three high-risk subgroups: English language learners (ELL), those with a specific learning disability (LD), and those identified as both LD and ELL (LD-ELL) in students in Grades 3–10. The authors were particularly interested in whether variability existed between initial status and the growth trajectories of the three high-risk groups on measures of spelling, fluency, and reading comprehension across the school year and whether this variability was differentiated because of socioeconomic status (SES) as defined by free and reduced lunch (FRL) status. Results indicate that all high-risk groups began the year at substantially lower levels than their GenEd peers, with the largest differences seen between the LD-ELL students and the other subgroups. Further results suggest that students who are in the high-risk subgroups and also qualify for FRL perform significantly worse than their peers in similar risk status groups who do not qualify for FRL, demonstrating the significant impact of SES on academic outcomes for all groups.
Reactivity to Stress and the Cognitive Components of Math Disability in Grade 1 Children
Authors: MacKinnon McQuarrie Maureen A. , Siegel Linda S. , Perry Nancy E. , Weinberg Joanne
Published: November 2012

This study investigated the relationship among working memory, processing speed, math performance, and reactivity to stress in 83 Grade 1 children. Specifically, 39 children with math disability (MD) were compared to 44 children who are typically achieving (TA) in mathematics. It is the first study to use a physiological index of stress (salivary cortisol levels) to measure children’s reactivity while completing tasks that assess the core components of MD: working memory for numbers, working memory for words, digits backward, letter number sequence, digit span forward, processing speed for numbers and words, block rotation, and math tasks. Grade 1 children with MD obtained significantly lower scores on the letter number sequence and quantitative concepts tasks. Higher levels of reactivity significantly predicted poorer performance on the working memory for numbers, working memory for words, and quantitative concepts tasks for Grade 1 children, regardless of math ability. Grade 1 children with MD and higher reactivity had significantly lower scores on the letter number sequence task than the children with MD and low reactivity. The findings suggest that high reactivity impairs performance in working memory and math tasks in Grade 1 children, and young children with high reactivity may benefit from interventions aimed at lowering anxiety in stressful situations, which may improve learning.
“Changing the Way I Teach”
Authors: Dierking Rebecca C. , Fox Roy F.
Published: November 2012

In this article, the authors examine the effect of a National Writing Project professional development model on a group of middle school writing teachers. The authors examine how contact with other professionals in intensive week-long sessions as well as mentoring from the professional development coach affected the teachers’ concept of themselves as professionals, as writers, and as colleagues, as well as how this attitudinal change affected their classrooms and students. The authors begin with an overview of recent scholarship on teacher “empowerment,” efficacy, and the National Writing Project. The authors then explicate their methodology and findings from this 2-year study, including how advanced knowledge builds confidence, how autonomy sustains empowerment, and how support can strengthen teachers, whereas other disempowering forces can negatively affect teacher actions. Implications for other professional development models as well as for future National Writing Project endeavors are included.
Gender and consociational power-sharing in Northern Ireland
Authors: Hayes Bernadette C. , McAllister Ian
Published: November 2012

Designing political arrangements is the most viable approach to resolving inter-communal divisions in post-conflict societies. Yet women are frequently ill-served by such peace settlements, since gender equality is often sacrificed in an effort to resolve conflicts over national identity. Northern Ireland is no exception to this trend. Although the 1998 Northern Ireland Agreement made specific provision for gender equality, it was primarily framed in terms of national identity. This article examines to what extent this focus on inter-communal ethnic division undermined support for the Agreement among women. Using data from the 2010 Northern Ireland Election Survey, we examine gender differences in attitudes towards the consociational institutions of government. The results show a significant gender gap in support for the institutional arrangements that were established by the Agreement. We propose and test three explanations to account for this gender gap.
The unintended consequences of the Helsinki Final Act: A path emergence theory perspective
Authors: Hong Ki-Joon
Published: November 2012

This article examines the unintended consequences of the 1975 Helsinki Final Act − a political agreement among the 35 participating states in the Conference on Security and Cooperation in Europe (CSCE). The primary objective of this article is to explain the unintended consequences of the CSCE security regime in terms of path emergence. ‘Path emergence’ is presented as a conceptual apparatus to explain the emergent properties exhibited within a complex adaptive system. The path emergence theory highlights four explanatory metaphors: morphogenetic fields, self-organized criticality, social resonance, and co-evolution. These metaphors serve as conceptual linchpins for the case analysis of the unintended consequences of the CSCE security regime. This article suggests that the CSCE embedded within it the properties of path emergence, which in turn contributed to the end of the Cold War in Europe.
Coronary and Systemic Arterial Physiology and Immunohistochemical Markers Related to Early Coronary Arterial Lesions in Beagle Dogs Given the Potassium Channel Opener, ZD6169, or the Endothelin Receptor Antagonist, ZD1611
Authors: Jones Huw Bowen , Björkman Jan-Arne , Schofield Jason
Published: November 2012

We evaluated immunohistochemistry (von Willebrand Factor [vWF] or fibrinogen) and systemic and coronary arterial physiological parameters in beagle dogs to investigate early arterial lesions induced by the potassium channel opener, ZD6169, or the endothelin receptor antagonist, ZD1611. Dogs given an oral dose of ZD6169 (experiment 1) were terminated 1 day later and showed arterial and myocardial lesions. Minimal arterial lesions exhibited few condensed medial smooth muscle cells only, with others showing segmental medial necrosis occasionally with medial/adventitial acute inflammation. Intercellular immunostaining was seen in ostensibly normal tissue, where no pathology was present in conventionally stained sections. vWF and fibrinogen are valuable tools for detecting disruption of arterial integrity. In experiment 2, 2 dogs were given a single high dose of ZD6169 or ZD1611 and BP/HR monitored by conventional measures or telemetry. Substantially reduced systolic/diastolic BP and increased HR occurred within 10 min of ZD6169 infusion: ZD1611 caused minor BP decrease and HR increase. In experiment 3, both drugs given to anaesthetized dogs induced markedly exaggerated systolic phasic forward and reverse flow in left descending and right coronary arteries. Diastolic coronary artery flows were unaffected with ZD1611 and increased slightly with ZD6169. In both coronary arteries, the ZD1611-induced increase in flows paralleled decreased resistance.
Toxicology and Carcinogenesis Study of Senna in C3B6.129F1-Trp53tm1Brd N12 Haploinsufficient Mice
Authors: Surh Inok , Brix Amy , French John E. , Collins Bradley J. , Sanders J. Michael , Vallant Molly , Dunnick June K.
Published: November 2012

Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1- Trp53tm1Brd N12 haploinsufficient (p53+/−) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53+/− mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53+/− males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53+/− mouse model. There was no neoplastic change when senna was administered to p53+/− mouse.
Evaluation of Expression Profiles of Hematopoietic Stem Cell, Endothelial Cell, and Myeloid Cell Antigens in Spontaneous and Chemically Induced Hemangiosarcomas and Hemangiomas in Mice
Authors: Kakiuchi-Kiyota Satoko , Crabbs Torrie A. , Arnold Lora L. , Pennington Karen L. , Cook Jon C. , Malarkey David E. , Cohen Samuel M.
Published: November 2012

It is unclear whether the process of spontaneous and chemically induced hemangiosarcoma and hemangioma formation in mice involves the transformation of differentiated endothelial cells (ECs) or recruitment of multipotential bone marrow–derived hematopoietic stem cells or endothelial progenitor cells (EPCs), which show some degree of endothelial differentiation. In the present study, immunohistochemical staining for hematopoietic stem cell markers (CD45 and CD34), EC markers (vascular endothelial growth factor receptor 2 [VEGFR2], CD31, and factor VIII–related antigen), and a myeloid lineage marker (CD14) was employed to better define the origin of hemangiosarcomas and hemangiomas in mice. Staining was negative for CD45, factor VIII–related antigen, and CD14 and positive for CD34, VEGFR2, and CD31, indicating that mouse hemangiosarcomas and hemangiomas are composed of cells derived from EPCs expressing CD34, VEGFR2, and CD31 but not factor VIII–related antigen. The lack of CD45 expression suggests that mouse vascular tumors may arise from EPCs that are at a stage later than hematopoietic stem cells. Since factor VIII–related antigen expression is known to occur later than CD31 expression in EPCs, our observations may indicate that these tumor cells are arrested at a stage prior to complete differentiation.  In addition, myeloid lineage cells do not appear to contribute to hemangiosarcoma and hemangioma formation in mice.
Adult Recurrent Respirator Papillomatosis
Authors: Suter‐Montano Teresita , Montaño Efraim , Martínez Carmen , Plascencia Teresita , Sepulveda Mayra T. , Rodríguez Miguel
Published: November 2012

Objective

To determine a new therapeutic approach using granulocyte monocyte–colony‐stimulating factor (GM‐CSF) and pegylated interferon alpha 2a (Peg‐IFNα‐2a) as adjuvant therapy in patients with adult recurrent respiratory papillomatosis.

Study Design

Descriptive observational clinical trial.

Setting

Departments of Otolaryngology and Immunology.

Methods

Fourteen patients with adult recurrent respiratory papillomatosis were examined regarding medical history and number of operations before and after treatment. Voice disorder and glottal stop were evaluated using the Voice‐Related Quality‐of‐Life instrument. Papilloma staging was determined using the Coltera/Derkay diagram. The patients received Peg‐IFNα‐2a at 180 mcg weekly for 6 months. In the third month, the patients began GM‐CSF treatment at 400 mcg weekly for 2 months. The patients were observed for 12 months after treatment ended.

Results

Eleven patients met the study criteria; 3 patients had tracheotomies before treatment, and they were decannulated after treatment. Before treatment, the scale of voice quality ranged from 34 to 45 points (mean, 38.31). After treatment, the range was 12 to 35 points (mean, 21.09; P <. 001). Prior to therapy, the glottal stop ranged from 50% to 90% (average, 62.27%). After therapy, the range decreased to 0% to 15% (mean, 4.63%; P <. 001). The number of surgical interventions decreased. Two patients each had 1 surgical intervention after treatment began.

Conclusion

A new adjuvant treatment based on immunogenetic mechanisms against human laryngeal papilloma virus, with expectations of reducing disease aggressiveness and the number of operations, avoids the risks of surgery.

Implication for Practice

Peg‐IFNα‐2a and GM‐CSF is an adjuvant therapy for treating adult recurrent respiratory papillomatosis.
Climate and environmental change and the potential for greening African cities
Authors: Simon David
Published: November 2012

Green economic investment has become a tool for technological innovation, energy efficiency, employment generation and environmental improvement that simultaneously mitigates and/or promotes some forms of adaptation to climate change. There is no single recipe for greening urban economies and increasing their environmental change resilience, but effective and flexible governance appears important. Many green economic measures can potentially promote prosperity and environmental resilience in different urban contexts. The links are complex and sometimes problematic. Conflicts of vision, interest and strategy may be deep-seated, leading to delays, sub-optimal outcomes or failure. Sometimes, too, unintended consequences adversely affect accessibility or equity. This article surveys the state of the art in relation to African towns and cities, illustrated with pertinent examples. Although urban greening is less advanced than in other regions, partly because of limited industrialisation, such investment in Africa has the potential to address longstanding development-environment problems, quality of life and livelihood sustainability and well as mitigating and adapting to climate change.
‘Beyond the golden triangle’: Biotechnology incubation in the East Midlands region of the UK
Authors: Smith David J , Ehret Michael
Published: November 2012

Policy changes by the UK Government in the 1990s led to the setting up of a large number of technology incubators specializing in biotechnology. A feature of these biotechnology incubators is that they were not confined to established life science intensive regions like the South East and East Anglia (Sainsbury, 1999), but spread across the UK. This study presents an in-depth case study of one of these biotechnology incubators. It provides insights into the contribution of incubators to the development of the biotechnology sector in the regions outside the ‘golden triangle’ (Mueller et al., 2012; Mullins, 2005) of Cambridge-London-Oxford. It identifies service-based business models as an attractive entry-mode for start-up firms in these regions and shows services to be the main contributor to job creation. The study contributes to closing some of the gaps in research into the relationship between technology incubation and economic development. In particular it identifies local factors conditioning the performance of local economies, business models, and incubation, particularly in the context of policies designed to promote the growth of technology-based start-up and spin-off companies as avenues for economic development and transformation.
Urban tourism, economic regeneration and inclusion: Evidence from South Africa
Authors: Rogerson Christian M
Published: November 2012

Tourism is one of the fastest growing economic sectors in sub-Saharan Africa. Although African tourism is dominated by nature tourism and cultural tourism products it must be appreciated that a large segment of the continent’s tourism economy is urban-based and that urban tourism represents a significant element of the continent’s expanding tourism economy. From analysis of the post-apartheid South African experience it is argued that debates about resurgent African urban development and the economic dynamics of urban Africa should not overlook the potential contribution of urban tourism for both driving economic growth and promoting inclusive development.
Agglomeration economies in the neighbourhood? Evidence from German cities
Authors: Neumann Uwe , Geißler Helmut , Jakubowski Peter
Published: November 2012

In urban renewal policy, it has become a widespread goal to revitalise neighbourhood economies. The rationale for these measures derives, to a great extent, from the concept of regional economic clusters, and, not surprisingly, one of their key objectives is to activate local inter-firm cooperation. This article examines the neighbourhood-related requirements and commitment of small firms. It draws on the results of a case study incorporating five German cities in which the neighbourhood-oriented applicability of economic policy was put to the test. As expected, it is unlikely for most small enterprises in urban renewal areas to engage in inter-firm cooperation focusing on the transfer of highly specialised knowledge. However, many small firms in inner city quarters appreciate neighbourhood characteristics as important location factors, and willingness to support local improvement efforts is relatively high, particularly among firms which operate successfully. The study suggests that there is a case for public policy to encourage small firms to participate in neighbourhood-based initiatives.
Apoptosis in Normal and Coxiella burnetii–Infected Placentas From Alaskan Northern Fur Seals (Callorhinus ursinus)
Authors: Myers E. , Ehrhart E. J. , Charles B. , Spraker T. , Gelatt T. , Duncan C.
Published: November 2012

In 2010, Coxiella burnetii was identified in 75% of northern fur seal placentas from a single rookery in Alaska, but nothing was known about the significance of this organism in the population. Although many infectious organisms cause increased cell death, C. burnetii has been shown to suppress apoptosis of the host macrophages as an intracellular survival mechanism. To determine if infection induces a similar functional change in the placenta, immunohistochemistry for antibodies to cleaved caspase-3 (activated caspase-3) and the (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) technique were used to compare the amount of placental apoptosis in infected and noninfected placentas. There was a statistically significant difference in the frequency of apoptotic cells between infected and uninfected placentas, with more apoptosis identified in the uninfected placentas. This finding suggests that the survival mechanism of C. burnetii in host macrophages to reduce apoptosis may also be utilized in trophoblasts. The significance of decreased trophoblastic apoptosis for the northern fur seal fetus requires further investigation.
Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma
Authors: Frantz A. M. , Sarver A. L. , Ito D. , Phang T. L. , Karimpour-Fard A. , Scott M. C. , Valli V. E. O. , Lindblad-Toh K. , Burgess K. E. , Husbands B. D. , Henson M. S. , Borgatti A. , Kisseberth W. C. , Hunter L. E. , Breen M. , O’Brien T. D. , Modiano J. F.
Published: November 2012

We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
Identifying Personality Subtypes Based on the Five-Factor Model Dimensions in Male Prisoners
Authors: Claes Laurence , Tavernier Geert , Roose Annelore , Bijttebier Patricia , Smith Sarah Francis , Lilienfeld Scott O.
Published: November 2012

The current study was designed to identify personality subtypes on the basis of the five-factor model dimensions in male prisoners. Participants included 110 Flemish male prisoners assessed by means of the Neuroticism, Extraversion, Openness Five Factor Inventory and different symptom, personality, and coping measures. We found two clusters: an emotionally stable/resilient cluster and an aggressive/undercontrolled cluster. Prisoners within the aggressive/undercontrolled cluster scored significantly higher on almost all Minnesota Multiphasic Personality Inventory–2 basic scales, (in)direct aggression measures, and depressive coping scales compared with resilients. They also scored higher on drug abuse and committed more sexual offenses than resilient prisoners. These two personality subtypes bear theoretically and practically important implications for psychopathy subtypes and different pathways to criminal offenses.
The Effect of a Cognitive Treatment Program for Male and Female Juvenile Offenders
Authors: McGlynn Adrea Hahn , Hahn Philip , Hagan Michael P.
Published: November 2012

This study assessed the effectiveness of a cognitive intervention treatment program for juvenile offenders, which is called the Juvenile Cognitive Intervention Program. The program was provided to incarcerated delinquents at three juvenile correctional facilities in Wisconsin. The results indicated that using the How I Think (HIT) Questionnaire as a measure of change, significant improvement in reducing cognitive distortions were found across age groups and gender, and included individuals who were unable to successfully complete the program the first time and then completed it successfully. The HIT is a measure of cognitive distortions that are associated with delinquent thinking patterns and behavior. Cognitive change is a major focus of treatment programs in juvenile corrections as there has been substantive research demonstrating a link to reduced delinquent and later criminal behavior.
Positive Portrayals of Feminist Men Increase Men’s Solidarity With Feminists and Collective Action Intentions
Authors: Wiley Shaun , Srinivasan Ruhi , Finke Elizabeth , Firnhaber Joseph , Shilinsky Alyssa
Published: November 2012

The present study examined whether positive portrayals of feminist men could increase men’s sense of solidarity with feminists and, through it, their intentions to engage in collective action in support of women. A sample of 102 mostly White men between the ages of 18 and 63 was recruited from Mechanical Turk, an online crowdsourcing marketplace. They were exposed to a short article either portraying feminist men in a positive light, a negative light, or describing the history of feminism without mentioning men. Men who read the positive portrayal article expressed more solidarity with feminists and greater intentions to engage in collective action in support of women than men who read either the history of feminism article or the negative portrayal article. Feminist solidarity fully mediated the relationship between positive portrayals of feminist men and collective action intentions. Consistent with research among women, the findings demonstrate that feeling connected to feminists is an important antecedent of men’s collective action in support of women. They also suggest a novel approach for involving men in collective action in support of women: building a positive image of feminist men. The implications of the findings for the men’s role in the feminist movement are discussed.
How Supportive of Their Specific Purposes Do Youth Believe Their Family and Friends Are?
Authors: Moran Seana , Bundick Matthew J. , Malin Heather , Reilly Timothy S.
Published: November 2012

Prior studies have found that youth reporting a general sense that “I have a purpose” also describe having social supports that enhance thriving. This study links specific social supports to specific purposes described by youth. We examined whether developmental level, social-structural supports of gender and ethnicity, and close relationship supports of family and friends explained (a) how likely youth were to describe three dimensions of a specific purpose content (intention, engagement, and beyond-the-self reasons), and (b) how youth with specified purposes used social supports to pursue those purposes. Youth in higher grade levels were more likely to describe their future plans, activities that pursued those plans, and reasons that considered consequences to others as well as themselves. Non-White ethnicity and higher friend support also increased the likelihood of youth expressing future plans. Youth with purposes sought or created—then integrated into a tailored support network— purpose-specific benefits from their families, opportunities to engage, and institutions.