bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Monoclonal B Lymphocytosis versus Rai 0 Chronic Lymphocytic Leukemia: A Comparison of Cellular, Cytogenetic, Molecular, and Clinical Features
Authors: Morabito Fortunato , Mosca Laura , Cutrona Giovanna , Agnelli Luca , Tuana Giacomo , Ferracin Manuela , Zagatti Barbara , Lionetti Marta , Fabris Sonia , Maura Francesco , Matis Serena , Gentile Massimo , Vigna Ernesto , Colombo Monica , Massucco Carlotta , Recchia Anna Grazia , Bossio Sabrina , De Stefano Laura , Ilariucci Fiorella , Musolino Caterina , Molica Stefano , Di Raimondo Francesco , Cortelezzi Agostino , Tassone Pierfrancesco , Negrini Massimo , Monti Sara , Rossi Davide , Gaidano Gianluca , Ferrarini Manlio , Neri Antonino
Published: September 2013

Purpose: To investigate the incidence and clinical relevance of classic and new prognostic markers, IGHV gene mutational status, and chromosomal abnormalities in clinical monoclonal B lymphocytosis (cMBL) compared with Rai stage 0 chronic lymphocytic leukemia (Rai0-CLL).

Experimental Design: A group of 136 patients with cMBL and a group of 216 Rai0-CLL cases were investigated prospectively.

Results: IGHV-mutated cases were significantly more frequent among cMBLs (P = 0.005), whereas the distribution of CD38 and ZAP-70 positive cases, of patients with NOTCH1 and SF3B1 mutations or exhibiting the major CLL cytogenetic abnormalities, was similar in the two groups. Moreover, no significant differences were found either in IGHV/IGHD/IGHJ gene usage or in the overall prevalence of stereotyped IGHV gene sequences. Cells from cMBL and Rai0-CLL exhibited similar gene and microRNA (miRNA) signatures; in addition, when grouped according to the IGHV mutational status, IGHV-unmutated cases showed different transcriptional signatures compared with IGHV-mutated patients, irrespective of the cMBL or Rai0-CLL classification. cMBL diagnosis per se was predictive of longer progression-free survival.

Conclusions: Our study based on a prospective series of patients indicates that no major differences exist between the circulating cells from cMBL and Rai0-CLL, at least based on a comparison of the markers used in the study. This possibly suggests that the two conditions mainly differ in the initial size of the monoclonal cell population, which may influence the subsequent timing of clonal expansion and clinical manifestations. Clin Cancer Res; 19(21); 5890–900. ©2013 AACR.
Targeted Nanomedicine for Suppression of CD44 and Simultaneous Cell Death Induction in Ovarian Cancer: An Optimal Delivery of siRNA and Anticancer Drug
Authors: Shah Vatsal , Taratula Oleh , Garbuzenko Olga B. , Taratula Olena R. , Rodriguez-Rodriguez Lorna , Minko Tamara
Published: September 2013

Purpose: The proposed project is aimed at enhancing the efficiency of epithelial ovarian cancer treatment and reducing adverse side effects of chemotherapy using nanotechnology. Overexpression of the CD44 membrane receptor results in tumor initiation, growth, cancer stem cells' specific behavior, development of drug resistance, and metastases. We hypothesize that a developed cancer-targeted delivery system that combines CD44 siRNA with paclitaxel would successfully deliver its payload inside cancer cells, effectively induce cell death, and prevent metastases.

Experimental Design: We synthesized, characterized, and tested a nanoscale-based drug delivery system (DDS) containing a modified polypropylenimine (PPI) dendrimer as a carrier; anticancer drug paclitaxel as a cell death inducer; a synthetic analog of luteinizing hormone–releasing hormone (LHRH) peptide as a tumor-targeting moiety; and siRNA targeted to CD44 mRNA. The proposed DDS was tested in vitro and in vivo using metastatic ovarian cancer cells isolated from patients with malignant ascites.

Results: We found that in contrast with cells isolated from primary tumors, CD44 was highly overexpressed in metastatic cancer cells. Treatment with the proposed tumor-targeted nanoscale-based nucleic acid and DDS led to the suppression of CD44 mRNA and protein, efficient induction of cell death, effective tumor shrinkage, and prevention of adverse side effects on healthy organs.

Conclusion: We show a high therapeutic potential for combinatorial treatment of ovarian carcinoma with a novel DDS that effectively transports siRNA targeting to CD44 mRNA simultaneously with cytotoxic agents. Clin Cancer Res; 19(22); 6193–204. ©2013 AACR.
GITR Pathway Activation Abrogates Tumor Immune Suppression through Loss of Regulatory T-cell Lineage Stability
Authors: Schaer David A. , Budhu Sadna , Liu Cailian , Bryson Campbell , Malandro Nicole , Cohen Adam , Zhong Hong , Yang Xia , Houghton Alan N. , Merghoub Taha , Wolchok Jedd D.
Published: September 2013

Ligation of GITR (glucocorticoid-induced TNF receptor-related gene, or TNFRSF18) by agonist antibody has recently entered into early-phase clinical trials for the treatment of advanced malignancies. Although the ability of GITR modulation to induce tumor regression is well documented in preclinical studies, the underlying mechanisms of action, particularly its effects on CD4+Foxp3+ regulatory T cells (Treg), have not been fully elucidated. We have previously shown that GITR ligation in vivo by agonist antibody DTA-1 causes more than 50% reduction of intratumor Tregs with down modulation of Foxp3 expression. Here, we show that the loss of Foxp3 is tumor dependent. Adoptively transferred Foxp3+ Tregs from tumor-bearing animals lose Foxp3 expression in the host when treated with DTA-1, whereas Tregs from naïve mice maintain Foxp3 expression. GITR ligation also alters the expression of various transcription factors and cytokines important for Treg function. Complete Foxp3 loss in intratumor Tregs correlates with a dramatic decrease in Helios expression and is associated with the upregulation of transcription factors, T-Bet and Eomes. Changes in Helios correspond with a reduction in interleukin (IL)-10 and an increase in IFN-γ expression in DTA-1–treated Tregs. Together, these data show that GITR agonist antibody alters Treg lineage stability inducing an inflammatory effector T-cell phenotype. The resultant loss of lineage stability causes Tregs to lose their intratumor immune-suppressive function, making the tumor susceptible to killing by tumor-specific effector CD8+ T cells. Cancer Immunol Res; 1(5); 320–31. ©2013 AACR.
Patients' Perception of Surgical Outcomes and Quality of Life after Retroperitoneoscopic and Open Pyeloplasty
Authors: Khoder Wael Y. , Waidelich Raphaela , Becker Armin J. , Karl Alexander , Haseke Nicolas , Bauer Ricarda M. , Stief Christian G. , Bachmann Alexander , Ebinger Mundorff Nicole
Published: September 2013

Purpose: To report postoperative health-related quality of life (HRQoL) and patients' subjective evaluations of open pyeloplasty (OP) and retroperitoneoscopic pyeloplasty (RP) and influences on preoperative counselling. Methods: 107 patients (age 16-80 years, mean 31.5) with symptomatic primary ureteropelvic junction obstruction who underwent OP (32) or RP (75) were evaluated prospectively. HRQoL was evaluated using Short Form 36 (SF-36) questionnaires with 1 year follow-up. Operative outcomes were evaluated using a self-designed questionnaire regarding cosmetic outcomes, objective postoperative/current pain, convalescence and return to work. Results: The mean operative time was 174.4 vs. 161.4 min for RP versus OP, respectively, without intraoperative complications/conversions. There was an advantage for RP - except for two domains - without significance in any of the eight SF-36 domain scores. An advantage favouring RP in all aspects of the second questionnaire with significance in four aspects (cosmetic results, scar length, pain and convalescence) was found. Five weeks postoperatively, 58.7% (RP) vs. 25.8% (OP) were fully convalescent compared to 87.0% (RP) vs. 71.0% (OP) at 8 weeks. Similarly, 58.7 vs. 45.1% returned work 5 weeks postoperatively while 93.5 vs. 74.2% did so after 8 weeks, respectively. The small sample size, more questions on satisfaction/regret and mixed design are the main study limitations. Conclusion: RP provides the same functional results beside earlier convalescence, better HRQoL and patients' convenience with surgery, which favours its inclusion in preoperative counselling providing patients with realistic postoperative expectations.
Orbital Lymphoma Mimicking Lacrimal Gland Pleomorphic Adenoma
Authors: Strianese Diego , Elefante Andrea , Matarazzo Francesco , Panico Angela , Ferrara Mariantonia , Tranfa Fausto
Published: September 2013

Purpose: To describe the case of a patient affected by orbital lymphoma mimicking pleomorphic adenoma of the lacrimal gland. Methods: This was a retrospective case report. Results: We present the case of a patient with 15-year history of slowly progressive left proptosis and inferomedial bulbar dislocation who had the presumptive diagnosis of lacrimal gland pleomorphic adenoma based on clinical and radiological features. The patient underwent lateral orbitotomy and lacrimal gland excision. Postoperative histological features were consistent with low-grade B-cell non-Hodgkin lymphoma. Conclusion: The accepted clinico-radiological criteria used for the diagnosis of lacrimal gland fossa lesions might have a certain false-positive rate, even in recent years. The initial surgical approach with the appropriate choice between fine-needle aspiration biopsies, intraoperative biopsies and lacrimal gland excisions might be a challenge.
Unfolded Protein Response Regulates Cardiac Sodium Current in Systolic Human Heart Failure
Authors: Gao Ge , Xie An , Zhang Jianhua , Herman Amanda M. , Jeong Euy-Myoung , Gu Lianzhi , Liu Man , Yang Kai-Chien , Kamp Timothy J. , Dudley Samuel C.
Published: September 2013

Background—

Human heart failure (HF) increases alternative mRNA splicing of the type V, voltage-gated cardiac Na
+
channel α-subunit (SCN5A), generating variants encoding truncated, nonfunctional channels that are trapped in the endoplasmic reticulum. In this work, we tested whether truncated Na
+
channels activate the unfolded protein response (UPR), contributing to SCN5A electric remodeling in HF.

Methods and Results—

UPR and SCN5A were analyzed in human ventricular systolic HF tissue samples and human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs). Cells were exposed to angiotensin II (AngII) and hypoxia, known activators of abnormal SCN5A mRNA splicing, or were induced to overexpress SCN5A variants. UPR effectors, protein kinase R-like ER kinase (PERK), calreticulin, and CHOP, were increased in human HF tissues. Induction of SCN5A variants with AngII or hypoxia or the expression of exogenous variants induced the UPR with concomitant downregulation of Na
+
current. PERK activation destabilized SCN5A and, surprisingly, K
v
4.3 channel mRNAs but not transient receptor potential cation channel M7 (TRPM7) channel mRNA. PERK inhibition prevented the loss of full-length SCN5A and K
v
4.3 mRNA levels resulting from expressing Na
+
channel mRNA splice variants.

Conclusions—

UPR can be initiated by Na
+
channel mRNA splice variants and is involved in the reduction of cardiac Na
+
current during human HF. Because the effect is not entirely specific to the SCN5A transcript, the UPR may play an important role in downregulation of multiple cardiac genes in HF.
Effects of Age and Aerobic Fitness on Myocardial Lipid Content
Authors: Sarma Satyam , Carrick-Ranson Graeme , Fujimoto Naoki , Adams-Huet Beverley , Bhella Paul S. , Hastings Jeffrey L. , Shafer Keri M. , Shibata Shigeki , Boyd Kara , Palmer Dean , Szczepaniak Edward W. , Szczepaniak Lidia S. , Levine Benjamin D.
Published: September 2013

Background—

Aging and sedentary lifestyles lead to cardiac atrophy, ventricular stiffening, and impaired diastolic function. Both conditions are marked by increased adiposity, which can lead to ectopic fat deposition in nonadipocyte tissues including the myocardium. The effect of excess intramyocardial fat on cardiac function in nonobese individuals is unknown.

Methods and Results—

Cardiac lipid content was measured by magnetic resonance spectroscopy in 153 healthy nonobese subjects with varying fitness levels quantified by peak oxygen uptake during treadmill exercise. Cardiac function (echo) and left ventricular (LV) filling pressures (right heart catheterization) were measured under varying preloads. LV stiffness was calculated from a curve fit of the diastolic portion of the pressure–volume curve. The strongest clinical predictors of lipid content were body mass index (β=+0.03; 95% confidence interval, 0.001–0.06) and peak oxygen uptake (β=−0.02; 95% confidence interval, −0.03 to −0.009;
R
2
=0.14;
P
<0.001). Subjects in the highest quintile had smaller LV end-diastolic volumes (68±13 versus 58±12 mL/m
2
;
P
<0.01) and decreased peak early mitral annular and increased peak late mitral inflow velocities. There were no differences in LV stiffness, but a leftward shift in the pressure–volume curve suggested a less distensible ventricle with increasing myocardial lipid levels. After adjusting for age, fitness, and body mass index, echocardiographic and morphometric differences among groups were attenuated and no longer significant.

Conclusions—

Body mass index and fitness levels are the strongest predictors of myocardial lipid content in nonobese humans. Cardiac lipid content is associated with decreased ventricular distensibility, and it may provide a causal mechanism linking changes in LV function related to age and fitness.
Thoracic Aortic Aneurysm Frequency and Dissection Are Associated With Fibrillin-1 Fragment Concentrations in Circulation
Authors: Marshall Lynn M. , Carlson Eric J. , O’Malley Jean , Snyder Caryn K. , Charbonneau Noe L. , Hayflick Susan J. , Coselli Joseph S. , LeMaire Scott A. , Sakai Lynn Y.
Published: September 2013

Rationale:

Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA.

Objective:

Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection.

Methods and Results:

Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6–5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6–5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4.

Conclusions:

Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection.
Intramyocardial Adiposity After Myocardial Infarction
Authors: Pouliopoulos Jim , Chik William W.B. , Kanthan Ajita , Sivagangabalan Gopal , Barry Michael A. , Fahmy Peter N.A. , Midekin Christine , Lu Juntang , Kizana Eddy , Thomas Stuart P. , Thiagalingam Aravinda , Kovoor Pramesh
Published: September 2013

Background—

Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI.

Methods and Results—

Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (
r
) with conduction velocity (
r
for adipose=0.39,
r
for discontinuity=0.45,
r
for collagen=0.26) and electrogram amplitude (
r
for adipose=0.73,
r
for contiguity=0.77,
r
for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (
P
>0.29). However, the MI+VT+ group demonstrated a significant (all
P
≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (
P
<0.001).

Conclusions—

Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.
Use of Remote Monitoring of Newly Implanted Cardioverter-Defibrillators
Authors: Akar Joseph G. , Bao Haikun , Jones Paul , Wang Yongfei , Chaudhry Sarwat I. , Varosy Paul , Masoudi Frederick A. , Stein Kenneth , Saxon Leslie A. , Curtis Jeptha P.
Published: September 2013

Background—

Current guidelines recommend using remote patient monitoring (RPM) for implantable cardioverter-defibrillators, but the patterns of adoption of this technology have not been described. Successful use of RPM depends on (1) the enrollment of the patient into an RPM system and (2) subsequent activation of RPM by the enrolled patient. We examined RPM enrollment and activation rates and the patient, physician, and institutional determinants of RPM use.

Methods and Results—

Information about the use of RPM-capable devices was obtained from the Boston Scientific Corporation ALTITUDE program and linked to the National Cardiovascular Data Registry ICD Registry. Patients were first categorized as RPM-enrolled and RPM-not enrolled, and the RPM-enrolled patients were further categorized into RPM-active and RPM-inactive groups based on whether they transmitted RPM data. Variables associated with RPM enrollment and activation were identified with the use of multivariable logistic regression. Among 39 158 patients with newly implanted RPM-capable devices, 62% (n=24 113) were RPM-enrolled. Of those enrolled, 76% (n=18 289, or 47% of the entire cohort) activated their device. RPM enrollment was highly variable among institutions. The hospital-specific median odds ratio for RPM enrollment was 3.43, signifying that physician or institutional factors are associated with RPM enrollment. In contrast, the hospital-specific median odds ratio for RPM activation was 1.69. Age, race, health insurance, geographic location, and health-related factors were similarly associated with both RPM enrollment and activation.

Conclusions—

RPM technology is used in less than half of eligible patients. Lack of enrollment into RPM systems is the major cause of underutilization, and this primarily relates to the local practice environment.
Long-Term Outcomes of Dilated Cardiomyopathy Diagnosed During Childhood
Authors: Alexander Peta M.A. , Daubeney Piers E.F. , Nugent Alan W. , Lee Katherine J. , Turner Christian , Colan Steven D. , Robertson Terry , Davis Andrew M. , Ramsay James , Justo Robert , Sholler Gary F. , King Ingrid , Weintraub Robert G.
Published: September 2013

Background—

Existing studies of childhood dilated cardiomyopathy deal mainly with early survival. This population-based study examines long-term outcomes for children with dilated cardiomyopathy.

Methods and Results—

The diagnosis of dilated cardiomyopathy was based on clinical, echocardiographic, and pathological findings. The primary study end point included time to the combined outcome of death or cardiac transplantation. There were 175 patients 0 to <10 years of age at the time of diagnosis. Survival free from death or transplantation was 74% (95% confidence interval, 67–80) 1 year after diagnosis, 62% (95% confidence interval, 55–69) at 10 years, and 56% (95% confidence interval, 46–65) at 20 years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial cardiomyopathy, and lower baseline left ventricular fractional shortening
Z
score were associated with increased risk of death or transplantation, as was lower left ventricular fractional shortening
Z
score during follow-up. At 15 years after diagnosis, echocardiographic normalization had occurred in 69% of surviving study subjects. Normalization was related to higher baseline left ventricular fractional shortening
Z
score, higher left ventricular fractional shortening
Z
score during follow-up, and greater improvement in left ventricular fractional shortening
Z
score. Children with lymphocytic myocarditis had better survival and a higher rate of echocardiographic normalization. At the latest follow-up, 100 of 104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer receiving pharmacotherapy.

Conclusions—

Death or transplantation occurred in 26% of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and ~1% per year thereafter. Risk factors for death or transplantation include age at diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction. The majority of surviving subjects are well and free of cardiac medication.
Automated External Defibrillators Inaccessible to More Than Half of Nearby Cardiac Arrests in Public Locations During Evening, Nighttime, and Weekends
Authors: Hansen Carolina Malta , Wissenberg Mads , Weeke Peter , Ruwald Martin Huth , Lamberts Morten , Lippert Freddy Knudsen , Gislason Gunnar Hilmar , Nielsen Søren Loumann , Køber Lars , Torp-Pedersen Christian , Folke Fredrik
Published: September 2013

Background—

Despite wide dissemination, use of automated external defibrillators (AEDs) in community settings is limited. We assessed how AED accessibility affected coverage of cardiac arrests in public locations.

Methods and Results—

We identified cardiac arrests in public locations (1994–2011) in terms of location and time and viewed them in relation to the location and accessibility of all AEDs linked to the emergency dispatch center as of December 31, 2011, in Copenhagen, Denmark. AED coverage of cardiac arrests was defined as cardiac arrests within 100 m (109.4 yd) of an AED and further categorized according to AED accessibility at the time of cardiac arrest. Daytime, evening, and nighttime were defined as 8
am
to 3:59
pm
, 4 to 11:59
pm
, and midnight to 7:59
am
, respectively. Of 1864 cardiac arrests in public locations, 61.8% (n=1152) occurred during the evening, nighttime, or weekends. Of 552 registered AEDs, 9.1% (n=50) were accessible at all hours, and 96.4% (n=532) were accessible during the daytime on all weekdays. Regardless of AED accessibility, 28.8% (537 of 1864) of all cardiac arrests were covered by an AED. Limited AED accessibility decreased coverage of cardiac arrests by 4.1% (9 of 217) during the daytime on weekdays and by 53.4% (171 of 320) during the evening, nighttime, and weekends.

Conclusions—

Limited AED accessibility at the time of cardiac arrest decreased AED coverage by 53.4% during the evening, nighttime, and weekends, which is when 61.8% of all cardiac arrests in public locations occurred. Thus, not only strategic placement but also uninterrupted AED accessibility warrant attention if public-access defibrillation is to improve survival after out-of-hospital cardiac arrest.
Initial Human Feasibility of Infusion Needle Catheter Ablation for Refractory Ventricular Tachycardia
Authors: Sapp John L. , Beeckler Christopher , Pike Robert , Parkash Ratika , Gray Christopher J. , Zeppenfeld Katja , Kuriachan Vikas , Stevenson William G.
Published: September 2013

Background—

Ablation of ventricular tachycardia (VT) is sometimes unsuccessful when ablation lesions are of insufficient depth to reach arrhythmogenic substrate. We report the initial experience with the use of a catheter with an extendable/retractable irrigated needle at the tip capable of intramyocardial mapping and ablation.

Methods and Results—

Sequential consenting patients with recurrent VT underwent ablation with the use of a needle-tipped catheter. At target sites, the needle was advanced 7 to 9 mm into the myocardium, permitting pacing and recording. Infusion of saline/iodinated contrast mixture excluded perforation and ensured intramyocardial deployment. Further infusion was delivered before and during temperature-controlled radiofrequency energy delivery through the needle. All 8 patients included (6 male; mean age, 54) with a mean left ventricular ejection fraction of 29% were refractory to multiple antiarrhythmic drugs, and 1 to 4 previous catheter ablation attempts (epicardial in 4) had failed. Patients had 1 to 7 (median, 2) VTs present or inducible; 2 were incessant. Some intramyocardial VT mapping was possible in 7 patients. A mean of 22 (limits, 3–48) needle ablation lesions were applied in 8 patients. All patients had at least 1 VT terminated or rendered noninducible. During a median of 12 months follow-up, 4 patients were free of recurrent VT, and 3 patients were improved, but had new VTs occur at some point during follow-up. Two died of the progression of preexisting heart failure without recurrent VT. Complications included tamponade in 1 patient and heart block in 2 patients.

Conclusions—

Intramyocardial infusion-needle catheter ablation is feasible and permits control of some VTs that have been refractory to conventional catheter ablation therapy, warranting further study.
C-Reactive Protein, but not Low-Density Lipoprotein Cholesterol Levels, Associate With Coronary Atheroma Regression and Cardiovascular Events After Maximally Intensive Statin Therapy
Authors: Puri Rishi , Nissen Steven E. , Libby Peter , Shao Mingyuan , Ballantyne Christie M. , Barter Phillip J. , Chapman M. John , Erbel Raimund , Raichlen Joel S. , Uno Kiyoko , Kataoka Yu , Nicholls Stephen J.
Published: September 2013

Background—

Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina). The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown.

Methods and Results—

The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent atheroma volume on intravascular ultrasound, CRP-modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc analysis to test associations between the changes in CRP levels with coronary disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had higher baseline (2.3 [1.1–4.7] versus 1.1 [0.5–1.8] mg/L;
P
<0.001) and lower follow-up CRP levels (0.8 [0.5–1.7] versus 1.6 [0.7–4.1] mg/L;
P
<0.001) versus those with increasing CRP levels (n=364). Multivariable analysis revealed a nonincreasing CRP level to independently associate with greater percent atheroma volume regression (
P
=0.01). Although the (log) change in CRP did not associate with MACE (hazard ratio, 1.18; 95% confidence interval, 0.93–1.50;
P
=0.17), the (log) on-treatment CRP associated significantly with MACE (hazard ratio, 1.28; 95% confidence interval, 1.04–1.56;
P
=0.02). On-treatment low-density lipoprotein cholesterol levels did not correlate with MACE (hazard ratio, 1.09; 95% confidence interval, 0.88–1.35;
P
=0.45).

Conclusions—

Following 24 months of potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation may be an important driver of residual cardiovascular risk in patients with coronary artery disease despite aggressive statin therapy.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT000620542.
Targeting Nuclear Import Shuttles, Importins/Karyopherins alpha by a Peptide Mimicking the NFκB1/p50 Nuclear Localization Sequence
Authors: Zienkiewicz Jozef , Armitage Amy , Hawiger Jacek
Published: September 2013

Background

We recently reported that a bifunctional nuclear transport modifier (
NTM
),
cSN
50.1 peptide, reduced atherosclerosis, plasma cholesterol, triglycerides, and glucose along with liver fat and inflammatory markers, in a murine model of familial hypercholesterolemia. We determined that
cSN
50.1 improved lipid homeostasis by modulating nuclear transport of sterol regulatory element‐binding proteins through interaction with importin β. Previous studies established that
cSN
50.1 and related
NTM
s also modulate nuclear transport of proinflammatory transcription factors mediated by binding of their nuclear localization sequences (
NLS
s) to importins/karyopherins α. However, selectivity and specificity of
NTM
s for importins/karyopherins α were undetermined.

Methods and Results

We analyzed interaction of the
NTM
hydrophilic module, N50 peptide, derived from the
NLS
of
NF
κB1/p50, with endogenous human importins/karyopherins α to determine the mechanism of
NTM
modulation of importin α‐mediated nuclear transport. We show that N50 peptide forms stable complexes with multiple importins/karyopherins α. However, only interaction with importin α5 (Imp α5) displayed specific, high‐affinity binding. The 2:1 stoichiometry of the N50‐Imp α5 interaction (

K
D

1
=73 nmol/L,

K
D

2
=140 nmol/L) indicated occupancy of both major and minor
NLS
binding pockets. Utilizing
in silico
3‐dimensional (3‐D) docking models and comparative structural analysis, we identified a structural component of the Imp α5 major
NLS
binding pocket that may stabilize N50 binding. Imp α5 also displayed rapid stimulus‐induced turnover, which could influence its availability for nuclear transport during the inflammatory response.

Conclusions

These results provide direct evidence that N50 peptide selectively targets Imp α5, encouraging further refinement of
NLS
‐derived peptides as new tools to modulate inflammatory disorders.
No Talk, Some Walk: Obama Administration First-Term Rhetoric on Climate Change and US International Climate Budget Commitments
Authors: Kincaid Graciela , Roberts J. Timmons
Published: September 2013

This paper examines the climate rhetoric and climate action of the Obama administration in its first term. It first traces the trajectory of the term “climate change” as used in 1,908 speeches by administration officials from January 2008 to December 2011; after an apex in 2009, the phrase nearly disappeared. Second, the article details the history of US international climate funding since 2009. In the Obama administration's first budget alone (Fiscal Year 2010), dedicated climate change foreign assistance increased from $321 million to $1.008 billion. Using anonymous administration sources, “fast start finance” reports, and the Congressional Research Service, the paper details the numbers and behind-the-scenes details of President Obama's apparent determination to prioritize climate finance despite powerful congressional opposition. Although these seemingly contradictory trends in rhetoric and finance can be seen as cohering in a highly strategic, energy-focused “two-level game” by the administration, the program's longevity is endangered.
Amounts of Artificial Food Colors in Commonly Consumed Beverages and Potential Behavioral Implications for Consumption in Children
Authors: Stevens Laura J. , Burgess John R. , Stochelski Mateusz A. , Kuczek Thomas
Published: September 2013

Artificial food colors (AFCs) are widely used to color foods and beverages. The amount of AFCs the Food and Drug Administration has certified over the years has increased more than 5-fold since 1950 (12 mg/capita/day) to 2012 (68 mg/capita/day). In the past 38 years, there have been studies of adverse behavioral reactions such as hyperactivity in children to double-blind challenges with AFCs. Studies that used 50 mg or more of AFCs as the challenge showed a greater negative effect on more children than those which used less. The study reported here is the first to quantify the amounts of AFCs in foods (specifically in beverages) commonly consumed by children in the United States. Consumption data for all foods would be helpful in the design of more challenge studies. The data summarized here should help clinicians advise parents about AFCs and beverage consumption.
Smooth Implementation of Critical Congenital Heart Defect Screening in a Newborn Nursery
Authors: Andrews Jennifer Purvis , Ross Ashley Sloan , Salazar Mary Ann , Tracy Neil Andrew , Burke Bryan LaDell
Published: September 2013

In January of 2012, University of Arkansas for Medical Sciences began implementation of a critical congenital heart disease screening program to identify newborns with structural heart defects. The screening used motion tolerant pulse oximeters in direct sequence to measure the oxygen levels in the right hand and either foot of eligible newborns. Exclusion criteria included echocardiogram prior to discharge, age greater than 7 days with continuous neonatal intensive care unit monitoring, or death or transfer prior to discharge. Of the 1905 infants screened, 3 infants failed screening. Two of the infants had atrial septal defects, and 1 had a patent foramen ovale, which was considered a false positive. After planning and education, the implementation of critical congenital heart disease pulse oximetry screening was successful. With only 1 false positive in our high-risk population, this should encourage other institutions to begin screening eligible infants.
Nipping Them in the Bud
Authors: Greig J. Michael
Published: September 2013

Civil conflicts constitute one of the most significant threats to human security. Understanding when belligerents are willing to undertake conflict management efforts is an important first step in better understanding how civil conflicts can be dealt with by the international community. In this article, I examine the occurrence of mediation in low-intensity conflicts. Drawing on insights from the war termination literature, I develop a theoretical argument that links mediation in low-intensity conflicts to the evolution of fighting. I argue that, while the characteristics of a conflict and its belligerents influence when mediation happens, how events unfold on the battlefield also influences the occurrence of mediation. I test this argument by looking at low-intensity conflicts in Africa from 1997 to 2004 using data on mediation in low-intensity conflicts and battle-level civil conflict events. The analysis highlights the important effect of battlefield outcomes and locations upon the occurrence of mediation in low-intensity conflicts.
Entangled Practices: Governance, Sustainable Technologies, and Energy Consumption
Authors: Ozaki Ritsuko , Shaw Isabel
Published: September 2013

In this article we provide a timely account of how sustainable technologies become entangled with cultural practices and thus co-evolve, influencing energy consumption. In doing so, we critique the approach current UK policy takes towards energy renewal and carbon reduction. We investigate the effectiveness of the social housing sector’s efforts to implement environmental policy initiatives that use a technology-driven approach. By looking at how social housing residents consume energy as part of domestic practices, we identify tensions between strategies to influence energy consumption by a housing association, and the ways residents incorporate sustainable technologies into everyday practices. Our findings reveal how sustainable technologies become enrolled in established practices: residents creatively develop novel routine strategies to accommodate new technologies to their daily routines. We contend that policy efforts to engender ‘behaviour change’ through a technology-driven approach have limitations. This approach ignores how practices become entangled, affecting energy consumption.
Political Emotions: A Role for Feelings of Affinity in Citizens’ (Dis)Engagements with Electoral Politics?
Authors: Manning Nathan , Holmes Mary
Published: September 2013

This article develops the concept of affinity as one means available in understanding how citizens make, or fail to make, connections with politics and politicians. It is argued that the disappearance of class from much political discourse has led to more emotional ways of relating to politics. We claim that the reflexivity involved in political deliberation must take account of people’s emotional responses to the political. We argue that one key element in these emotional responses is a feeling, or lack of feeling, of affinity. We propose that citizens often use feelings of likeness in their (dis)engagement with politicians, policies and parties. Understanding the emotional aspects of political (dis)engagement in this way is crucial in dealing with concerns about widespread disengagement from, and dissatisfaction with, electoral politics.
Urban Energy Policies and the Governance of Multilevel Issues in Cape Town
Authors: Jaglin Sylvy
Published: September 2013

The multiscalar challenges associated with urban energy policies are the cause of extensive interaction among multiple levels of government and social forces. However, these multilevel systems of action tend to reflect complex and unstable power and resistance patterns rather than stable co-operation processes. Thus, in this paper, a multilevel governance perspective is used as a starting point for understanding where and how multilevel interactions arise in an energy system as well as which issues are creating political conflict and the related consequences for the governance of urban energy policies. This approach is illustrated through a case study of Cape Town, which exemplifies a situation of conflicting policy and agendas at different levels of government, thus creating a great dispersion of initiatives across different scales. Integrating these initiatives within a broader coherent framework, however, is not only a technical matter. As urban energy policies deal with multilevel issues, they imply negotiating dynamic and complex compromises between different types of organisations and authorities while shaping their governance is also a matter of politics.
McJobs and Pieces of Flair
Authors: Treiber Linda Ann
Published: September 2013

This article offers strategies for teaching about rationality, bureaucracy, and social change using George Ritzer’s The McDonaldization of Society and its ideas about efficiency, predictability, calculability, and control. Student learning is facilitated using a series of strategies: making the familiar strange, explaining McDonaldization, self-investigation and discovery, and exploring and implementing alternatives. Through assignments, class exercises, and films, students contextualize modernity and its unintended negative consequences by viewing McDonaldization though the lenses of work and jobs. These strategies provide a framework to help students understand key concepts, critique McDonaldization, and formulate positive ways to cope with Weber’s iron cage.
Rites of Pedagogical Passage
Authors: Smollin Leandra M. , Arluke Arnold
Published: September 2013

This study examines the dynamics of the first-time teaching experience of graduate instructors, drawing on interview and focus group data from 35 sociology students in a doctoral program at a large university in the United States. Results indicate the majority of graduate instructors felt a great deal of anxiety due to challenges they faced when teaching their own course for the first time: challenges such as feelings of unpreparedness, constant and unremitting time demands, problems with students, a lack of confidence, and insufficient support. Instructors employed a number of informal strategies in attempts to mediate the personal and professional impact of these challenges. Strategies included adjusting expectations, making sacrifices, becoming savvy, and creating informal peer networks that provided social support and increased access to resources. Findings indicate the need for institutional-level changes, including how graduate student teaching is viewed within the discipline and the ways graduate instructors are supported and prepared to teach. This article concludes with specific recommendations for graduate programs and sociology departments of sociology.
Hearing Stories That Violate Expectations Leads to Emotional Broadcasting
Authors: Harber Kent D. , Podolski Peter , Dyer Lisbeth
Published: September 2013

Emotional Broadcaster Theory (EBT) proposes that the need to disclose turns people into news broadcasters whose stories inform others of major events. The present research tested whether the discrepancy theory of emotion explains emotional broadcasting. Study 1 showed that hearers anticipated being more strongly affected by and more likely to retell unusual stories (per discrepancy theory) than stories conveyed by a distressed teller (per emotional contagion theory). Study 2 tested whether the same unusual event (violence) would be disclosed more by people for whom violence is unexpected. As predicted, people with minimal exposure to violence regarded violence as more disturbing and as more likely to be disclosed than did those with extensive exposure to violence. Study 3 replicated Study 2, and showed that violence exposure moderated anticipated emotional arousal and disclosure only for violent events but not for unusual nonviolent events. Neither violence seeking nor social desirability confounded these results.
The Utility of the ‘Other’: German Representations of Sweden in the Second Half of the Eighteenth Century
Authors: Persson Mathias
Published: September 2013

This article analyses the representations of Sweden in a renowned and widely read German periodical, the Göttingische Anzeigen von gelehrten Sachen, during the period 1753–92. The investigation demonstrates how a European country could be imagined and put to use in a nearby state, where its mental and physical closeness gave it the ambiguous status of a proximate ‘other’. Although Anzeigen identified with the northern kingdom in many respects, Sweden’s nature and climate, indigenous Lapp population and remaining German provinces constituted a basis for representations of it as ‘other’ rather than ‘same’. Nonetheless, Sweden and its literati were usually put in a positive light due to the existence of extensive Hanoverian–Swedish networks, an ideological identification with Sweden’s estate society and a willingness to embrace useful Swedish models. Anzeigen’s favourable renderings of these models amounted to a ‘patriotic–cosmopolitan economy’, through which particularistic experiences could be turned into universal phenomena and transferred to foreign settings.
Posterior Tibial Slope and Further Anterior Cruciate Ligament Injuries in the Anterior Cruciate Ligament–Reconstructed Patient
Authors: Webb Justin M. , Salmon Lucy J. , Leclerc Etienne , Pinczewski Leo A. , Roe Justin P.
Published: September 2013

Background:

An injury to the anterior cruciate ligament (ACL) is a multifactorial event influenced by intrinsic and extrinsic risk factors. Recently, the geometry of the proximal tibia has come under focus as a possible risk factor for an ACL injury.

Hypothesis:

An increased posterior tibial slope is associated with an increased risk of further ACL injuries in the previously ACL-reconstructed patient.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

A total of 200 consecutive patients with isolated ACL ruptures who underwent primary reconstruction with hamstring autografts were enrolled in a prospective longitudinal study over 15 years. The posterior tibial slope was measured from a lateral knee radiograph by 2 blinded observers. The data were analyzed for the association between an increased posterior tibial slope and the incidence of further ACL injuries. Interobserver reliability of the posterior tibial slope measurements was assessed.

Results:

Radiographs and follow-up were available for 181 of the 200 enrolled patients. Fifty patients had a further injury to either the ACL graft or the contralateral knee. The mean posterior tibial slope of those with a further ACL injury was 9.9° compared with 8.5° for those with no further injury ( P = .001). The mean posterior tibial slope for those with both an ACL graft and contralateral ACL rupture was 12.9°. The odds of further ACL injuries after reconstruction were increased by a factor of 5, to an incidence of 59%, in those with a posterior tibial slope of ≥12°.

Conclusion:

An increased posterior tibial slope is associated with increased odds of a further ACL injury after ACL reconstruction. The increased risk is most pronounced in those with a posterior tibial slope of ≥12°.
Composites of sisal fiber/polypropylene based on novel vane extruder: Effect of interface and damage on mechanical properties
Authors: Wu Chengran , Jia Shikui , Chen Rongyuan , Huang Zan , Zhai Shufeng , Feng Yanhong , Yang Zhitao , Qu Jinping
Published: September 2013

Sisal fibers were pretreated by alkali and maleic anhydride, and then mixed with polypropylene to fabricate sisal fiber-reinforced composites by a self-made vane extruder based on elongational flow field. Maleic anhydride-grafted polypropylene was used as compatilizer to increase the fiber/matrix interactions. The influence of treatment on the fibers structure, the damage to fibers in processing, interfaces of composites and the mechanical properties of composites were investigated. It was observed that the surface of treated fibers was improved obviously compared with that of untreated fibers, which was believed to increase the adhesion between the fibers and matrix. However, the treated fibers were more likely to be damaged during processing. In comparison to unmodified system, the incorporation of treated fibers could significantly enhance the mechanical properties of composites, especially adding the compatilizer of maleic anhydride-grafted polypropylene. The flexural and impact strengths were maximum for the sisal fiber/polypropylene and maleic anhydride-grafted polypropylene composites, and its tensile strength was also improved significantly. The major contribution of this change should be that the morphology of fibers could be well preserved in elongational flow field, which based on the vane extruder showed a good application in fiber-reinforced composites.