bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary vascular function and exercise capacity in black sub-Saharan Africans
Authors: Simaga Bamodi , Vicenzi Marco , Faoro Vitalie , Caravita Sergio , Di Marco Giovanni , Forton Kevin , Deboeck Gael , Lalande Sophie , Naeije Robert
Published: July 2015

Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l−1·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max ( P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women.
Interactions between breathing rate and low-frequency fluctuations in blood pressure and cardiac intervals
Authors: Horsman H. M. , Peebles K. C. , Tzeng Y. C.
Published: July 2015

Evidence derived from spontaneous measures of cardiovagal baroreflex sensitivity (BRS) suggests that slow breathing at 6 breaths/min augments BRS. However, increases in BRS associated with slow breathing may simply reflect the frequency-dependent nature of the baroreflex rather than the modulation of baroreflex function by changes in breathing rate per se. To test this hypothesis we employed a crossover study design ( n = 14) wherein breathing rate and systolic arterial blood pressure (SAP) oscillation induced via the application of oscillating lower body negative pressure (OLBNP) were independently varied at fixed frequencies. Breathing rate was controlled at 6 or 10 breaths/min with the aid of a metronome, and SAP oscillations were driven at 0.06 Hz and 0.1 Hz using OLBNP. The magnitudes of SAP and R-R interval (cardiac period) oscillations were quantified using power spectral analysis, and the transfer function gain between SAP and R-R interval was used to estimate BRS. Linear mixed-effects models were used to examine the main effects and interactions between breathing rate and OLBNP frequency. There was no statistical interaction between breathing and OLBNP frequency ( P = 0.59), indicating that the effect of breathing rate on BRS did not differ according to OLBNP frequency (and vice versa). Additionally, there was no main effect for breathing rate ( P = 0.28). However, we observed a significant main effect for OLBNP frequency ( P = 0.01) consistent with the frequency-dependent nature of baroreflex. These findings suggest that increases in spectral indices of BRS reflect the frequency dependence of the baroreflex and are not due to slow breathing per se.
ErbB3–ErbB2 Complexes as a Therapeutic Target in a Subset of Wild-type BRAF/NRAS Cutaneous Melanomas
Authors: Capparelli Claudia , Rosenbaum Sheera , Berman-Booty Lisa D. , Salhi Amel , Gaborit Nadège , Zhan Tingting , Chervoneva Inna , Roszik Jason , Woodman Scott E. , Davies Michael A. , Setiady Yulius Y. , Osman Iman , Yarden Yosef , Aplin Andrew E.
Published: July 2015

The treatment options remain limited for patients with melanoma who are wild-type for both BRAF and NRAS (WT/WT). We demonstrate that a subgroup of WT/WT melanomas display high basal phosphorylation of ErbB3 that is associated with autocrine production of the ErbB3 ligand neuregulin-1 (NRG1). In WT/WT melanoma cells displaying high levels of phospho-ErbB3, knockdown of NRG1 reduced cell viability and was associated with decreased phosphorylation of ErbB3, its coreceptor ErbB2, and its downstream target, AKT. Similar effects were observed by targeting ErbB3 with either siRNAs or the neutralizing ErbB3 monoclonal antibodies huHER3-8 and NG33. In addition, pertuzumab-mediated inhibition of ErbB2 heterodimerization decreased AKT phosphorylation, cell growth in vitro, and xenograft growth in vivo. Pertuzumab also potentiated the effects of MEK inhibitor on WT/WT melanoma growth in vitro and in vivo. These findings demonstrate that targeting ErbB3–ErbB2 signaling in a cohort of WT/WT melanomas leads to tumor growth reduction. Together, these studies support the rationale to target the NRG1–ErbB3–ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas. Cancer Res; 75(17); 3554–67. ©2015 AACR.
Tumor-Promoting Effects of Myeloid-Derived Suppressor Cells Are Potentiated by Hypoxia-Induced Expression of miR-210
Authors: Noman Muhammad Zaeem , Janji Bassam , Hu Shijun , Wu Joseph C. , Martelli Fabio , Bronte Vincenzo , Chouaib Salem
Published: July 2015

Myeloid-derived suppressor cells (MDSC) contribute significantly to the malignant characters conferred by hypoxic tumor microenvironments. However, selective biomarkers of MDSC function in this critical setting have not been defined. Here, we report that miR-210 expression is elevated by hypoxia-inducible factor-1α (HIF1α) in MDSC localized to tumors, compared with splenic MDSC from tumor-bearing mice. In tumor MDSC, we determined that HIF1α was bound directly to a transcriptionally active hypoxia-response element in the miR-210 proximal promoter. miR-210 overexpression was sufficient to enhance MDSC-mediated T-cell suppression under normoxic conditions, while targeting hypoxia-induced miR-210 was sufficient to decrease MDSC function against T cells. Mechanistic investigations revealed that miR-210 modulated MDSC function by increasing arginase activity and nitric oxide production, without affecting reactive oxygen species, IL6, or IL10 production or expression of PD-L1. In splenic MDSC, miR-210 regulated Arg1, Cxcl12, and IL16 at the levels of both mRNA and protein, the reversal of which under normoxic conditions decreased T-cell–suppressive effects and IFNγ production. Interestingly, miR-210 overexpression or targeting IL16 or CXCL12 enhanced the immunosuppressive activity of MDSC in vivo, resulting in increased tumor growth. Taken together, these results provide a preclinical rationale to explore miR-210 inhibitory oligonucleotides as adjuvants to boost immunotherapeutic responses in cancer patients. Cancer Res; 75(18); 3771–87. ©2015 AACR.
LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival
Authors: Torres Sofía , Garcia-Palmero Irene , Herrera Mercedes , Bartolomé Rubén A. , Peña Cristina , Fernandez-Aceñero M. Jesús , Padilla Guillermo , Peláez-García Alberto , Lopez-Lucendo María , Rodriguez-Merlo Rufo , de Herreros Antonio García , Bonilla Félix , Casal J. Ignacio
Published: July 2015

Purpose: Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes in protein expression in colon cancer–associated fibroblasts compared with normal fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II patients.

Experimental Design: CAFs and NFs isolated from colon cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training, then quantitative PCR and IHC for validation in different cohorts of patients. Combined datasets were used for prediction of risk assessment at stages II and III.

Results: A desmoplastic signature composed of 32 proteins, highly specific for stromal components in colon cancer, was identified. These proteins were enriched for extracellular matrix organization components, TGFβ signaling pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques. LOXL2 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of patients. High expression of LOXL2 was associated with higher recurrence P = 0.001 HR, 5.38 [95% confidence interval (CI), 1.70–17.01] and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90–38.29). IHC analysis revealed a prognostic value for LOXL2 in stage II patients.

Conclusions: We identified LOXL2 to be associated with the outcome of colon cancer patients. Furthermore, it can be used to stratify patients at stages II and III for further therapeutic decisions. Clin Cancer Res; 21(21); 4892–902. ©2015 AACR.
Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations
Authors: Larrue Clément , Saland Estelle , Vergez François , Serhan Nizar , Delabesse Eric , Mansat-De Mas Véronique , Hospital Marie-Anne , Tamburini Jérôme , Manenti Stéphane , Sarry Jean Emmanuel , Récher Christian
Published: July 2015

We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT–mutated cell lines and cell samples from core binding factor–AML patients. In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK–ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. Mol Cancer Ther; 14(10); 2364–73. ©2015 AACR.
Validation of the Conventional Resection Criteria in Patients with Hepatocellular Carcinoma in Terms of the Incidence of Posthepatectomy Liver Failure and Long-Term Prognosis
Authors: Iguchi Kohta , Hatano Etsuro , Yamanaka Kenya , Tanaka Shiro , Taura Kojiro , Uemoto Shinji
Published: July 2015

Background/Aims: Resection criteria in hepatocellular carcinoma (HCC) should be established based on the risk of posthepatectomy liver failure (PHLF) and the survival benefit from hepatectomy. This study aimed at verifying the validity of the conventional criteria regarding the incidence of PHLF and the long-term prognosis of HCC patients. Methods: A retrospective study was performed on 265 patients who underwent major hepatectomy. Makuuchi's criteria and the future liver remnant plasma clearance rate of indocyanine green (ICGK-rem) ≥0.05 criterion were evaluated. Results: A total of 107 and 158 patients were within and beyond Makuuchi's criteria, respectively. Makuuchi's criteria were associated with the incidence of PHLF (p = 0.03) but not with its severity (p = 0.12). No differences in disease-free survival (DFS) or overall survival (OS) were observed between the groups (p = 0.75 and p = 0.94, respectively). Using the ICGK-rem ≥0.05 criterion, 223 and 42 patients were within and beyond the criterion, respectively. ICGK-rem was correlated with both the incidence of PHLF (p = 0.002) and its severity (p = 0.03). No differences in DFS or OS were observed between the groups (p = 0.75 and p = 0.29, respectively). Conclusions: Strict criteria are likely to preclude some patients from obtaining the greater survival benefits of hepatectomy. New criteria that consider patient prognosis are needed.
Cigarette Smoking and Carotid Plaque Echodensity in the Northern Manhattan Study
Authors: Yang Dixon , Iyer Sunil , Gardener Hannah , Della-Morte David , Crisby Milita , Dong Chuanhui , Cheung Ken , Mora-McLaughlin Consuelo , Wright Clinton B. , Elkind Mitchell S. , Sacco Ralph L. , Rundek Tatjana
Published: July 2015

Background: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multiethnic cohort. Methods: We analyzed 1,743 stroke-free participants (mean age 65.5 ± 8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors. Results: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1-5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a two fold increased risk of having GSM in quintile 1 (odds ratio (OR) = 2.17; 95% confidence interval (CI), 1.34-3.52), quintile 2 (OR = 2.33; 95% CI, 1.42-3.83), quintile 4 (OR = 2.05; 95% CI, 1.19-3.51), and quintile 5 (OR = 2.13; 95% CI, 1.27-3.56) but not in quintile 3 (OR = 1.18; 95% CI, 0.67-2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR = 1.46; 95% CI, 1.00-2.12), quintile 3 (OR = 1.56; 95% CI, 1.09-2.24), quintile 4 (OR = 1.66; 95% CI, 1.13-2.42), and quintile 5 (OR = 1.73; 95% CI, 1.19-2.51), but not in quintile 1 (OR = 1.05; 95% CI, 0.72-1.55). Conclusions: A nonlinear, V-shaped-like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at the highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of having only echodense plaques when compared to those who have never smoked. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events.
Serum Potassium, End-Stage Renal Disease and Mortality in Chronic Kidney Disease
Authors: Nakhoul Georges N. , Huang Haiquan , Arrigain Susana , Jolly Stacey E. , Schold Jesse D. , Nally Jr. Joseph V. , Navaneethan Sankar D.
Published: July 2015

Background/Aims: Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population. Methods: Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m2 and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models. Results: Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality. Conclusion: In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.
Pre-Transplant Weight Loss and Survival after Kidney Transplantation
Authors: Huang Edmund , Bunnapradist Suphamai
Published: July 2015

Background/Aims: We examined post-transplant survival among obese kidney candidates who were temporarily designated waitlist inactive (status 7) due to their weight. Methods: Using OPTN/United Network for Organ Sharing data, patient and graft survival of adult status 7 recipients with a registration body mass index (BMI) ≥30 kg/m2 (n = 328) were compared to all others (controls; n = 74,066). Status 7 recipients were then matched to controls to assess whether pre-transplant weight loss was associated with a survival benefit. Results: Median BMI at registration (38 vs. 27 kg/m2, p < 0.001) and transplant (36 vs. 27 kg/m2, p < 0.001) and reduction in BMI while waitlisted (-5.0 vs. 0.0%, p < 0.001) were higher among status 7 than controls. Patient (status 7: 87.3%; control: 89.3%; p = 0.90) and graft survival (status 7: 82.9%; control: 81.6%; p = 0.75) were similar over 4 years. There was no association between status 7 and mortality (HR 0.96, 95% CI 0.59-1.57) or graft loss (HR 0.95, 95% CI 0.66-1.38) in the overall population nor between matched status 7 recipients and controls (patient survival: 86.0 vs. 87.5%, p = 0.20; graft survival: 82.6 vs. 77.2%, p = 0.61). Conclusion: Among obese status 7 kidney candidates previously considered too obese for transplant, patient and graft survival were comparable to the general transplant population. No difference in survival was observed with pre-transplant weight loss.
Pro-Apoptotic Effects of Plasma from Patients with Cardiorenal Syndrome on Human Tubular Cells
Authors: Virzì Grazia Maria , de Cal Massimo , Day Sonya , Brocca Alessandra , Cruz Dinna N. , Castellani Chiara , Cantaluppi Vincenzo , Bolin Chiara , Fedrigo Marny , Thiene Gaetano , Valente Marialuisa , Angelini Annalisa , Vescovo Giorgio , Ronco Claudio
Published: July 2015

Background: The pathophysiology of Cardiorenal Syndrome Type 1 (CRS1) is widely studied, although the mechanisms by which renal tubular epithelial cells (TECs) cease to proliferate and embark upon terminal differentiation, following the initial insult of heart failure (HF), remain a key target. This study seeks to provide insight into the pathophysiological pathways in CRS1; we evaluated in vitro the effects of CRS1 plasma on TECs. Methods: We enrolled 40 acute HF patients and 15 controls (CTR) without HF or acute kidney injury (AKI). Ten out of 40 HF patients exhibited AKI at the time of admission for HF or developed AKI during hospitalization and were classified as CRS1. In vitro, cell viability, DNA fragmentation and caspase-3 levels were investigated in TECs incubated with HF, CRS1, and CTR plasma. We assessed inflammatory cytokines and NGAL expression at the gene and protein levels. Results: We observed a marked pro-apoptotic activity and a significantly increased in vitro level of apoptosis in TECs incubated with plasma from CRS1 patients compared to HF and CTR (p < 0.01). In the CRS1 group, the mRNA expression of IL-6, IL-18 and NGAL resulted significantly higher in TECs incubated with CRS1 plasma compared with those incubated with plasma from HF and CTR (p < 0.01). IL-6, IL-18, NGAL, and RANTES levels were significantly higher in TECs supernatant incubated with CRS1 plasma compared with HF patients and CTR plasma (p < 0.01). Conclusion: In vitro exposure to plasma from CRS1 patients altered the expression profile of TECs characterized by increases in proinflammatory mediators, release of tubular damage markers, and apoptosis.
Diaminodiphenyl Sulfone-Induced Hemolytic Anemia and Alopecia in a Case of Linear IgA Bullous Dermatosis
Authors: Akasaka Eijiro , Kayo Sato-Jin , Nakano Hajime , Ishii Norito , Hashimoto Takashi , Sawamura Daisuke
Published: July 2015

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease characterized by subepidermal blistering induced by IgA autoantibodies against several autoantigens in the basal membranous zone of the skin and mucosal tissue. Although diaminodiphenyl sulfone (DDS), also known as dapsone, is generally recognized as the first-line therapy for LABD, DDS can induce several severe side effects. We present a Japanese case of LABD with DDS-induced hemolytic anemia and alopecia. In the present case, the DDS-induced hemolytic anemia and hair loss made the DDS monotherapy difficult. When DDS is used in LABD patients with iron deficiency anemia (IDA), hemolytic anemia is concealed by IDA. It is thus necessary to carefully and frequently examine the laboratory data to find the signs of DDS-induced hemolytic anemia. Even though there is no literature on DDS-induced alopecia, alopecia was reported as one of the side effects of DDS in an FDA report, and, in our case, hair loss was improved after reducing its dosage. We have to recognize that alopecia is one of the side effects of DDS and that careful management is needed in order not to overlook the adverse side effects of DDS when treating LABD patients.
Individual and Combined Risk Factors for Incident Atrial Fibrillation and Incident Stroke: An Analysis of 3 Million At‐Risk US Patients
Authors: Chyou Janice Y. , Hunter Tina D. , Mollenkopf Sarah A. , Turakhia Mintu P. , Reynolds Matthew R.
Published: July 2015

Background

The incremental effects of risk factor combinations for atrial fibrillation (
AF
) and stroke are incompletely understood. We sought to quantify the risks of incident
AF
and stroke for combinations of established risk factors in a large
US
sample.

Methods and Results

Patients with no evidence of
AF
or stroke in 2007 were stratified by combinations of the following risk factors: heart failure, hypertension, diabetes, age 65 to 74, age ≥75, coronary artery disease, and chronic kidney disease. Patients with ≥2 of the first 5 or ≥3 of the first 7, classified as “high‐risk,” and an age‐matched sample of patients with fewer risk factors, classified as “low‐risk,” were followed over 2008–2010 for incident
AF
and stroke. Annualized incidence rates and risks were quantified for each combination of factors by using Cox regression. Annualized incidence rates for
AF
, stroke, and both were 3.59%, 3.27%, and 0.62% in 1 851 653 high‐risk patients and 1.32%, 1.48%, and 0.18% in 1 156 221 low‐risk patients, respectively. Among patients with 1 risk factor, those with age ≥75 had the highest hazards of incident
AF
and stroke (HR 9.2, 6.9). Among patients with 2 risk factors, those with age ≥75 and heart failure had the highest annualized incidence rates of
AF
and stroke (10.2%, 5.9%). The combination of age ≥75 and hypertension was prevalent and had the highest incidences of
AF
and stroke.

Conclusions

Adults with combinations of known risk factors are at increased risk of incident
AF
and stroke, but combinations of risk factors are not always additive.
Very Low Ventricular Pacing Rates Can Be Achieved Safely in a Heterogeneous Pacemaker Population and Provide Clinical Benefits: The CANadian Multi‐Centre Randomised Study‐Spontaneous AtrioVEntricular Conduction pReservation (CAN‐SAVE R) Trial
Authors: Thibault Bernard , Ducharme Anique , Baranchuk Adrian , Dubuc Marc , Dyrda Katia , Guerra Peter G. , Macle Laurent , Mondésert Blandine , Rivard Léna , Roy Denis , Talajic Mario , Andrade Jason , Nitzsché Rémi , Khairy Paul ,   the CAN‐SAVE R Study Investigators
Published: July 2015

Background

It is well recognized that right ventricular apical pacing can have deleterious effects on ventricular function. We performed a head‐to‐head comparison of the SafeR pacing algorithm versus
DDD
pacing with a long atrioventricular delay in a heterogeneous population of patients with dual‐chamber pacemakers.

Methods and Results

In a multicenter prospective double‐blinded randomized trial conducted at 10 centers in Canada, 373 patients, age 71±11 years, with indications for dual chamber
DC
pacemakers were randomized 1:1 to SafeR or
DDD
pacing with a long atrioventricular delay (250 ms). The primary objective was twofold: (1) reduction in the proportion of ventricular paced beats at 1 year; and (2) impact on atrial fibrillation burden at 3 years, defined as the ratio between cumulative duration of mode‐switches divided by follow‐up time. Statistical significance of both co‐primary end points was required for the trial to be considered positive. At 1 year of follow‐up, the median proportion of ventricular‐paced beats was 4.0% with
DDD
versus 0% with SafeR (
P
<0.001). At 3 years of follow‐up, the atrial fibrillation burden was not significantly reduced with SafeR versus
DDD
(median 0.00%, interquartile range [0.00% to 0.23%] versus median 0.01%, interquartile range [0.00% to 0.44%], respectively,
P
=0.178]), despite a persistent reduction in the median proportion of ventricular‐paced beats (10% with
DDD
compared to 0% with SafeR).

Conclusions

A ventricular‐paced rate <1% was safely achieved with SafeR in a population with a wide spectrum of indications for dual‐chamber pacing. However, the lower percentage of ventricular pacing did not translate into a significant reduction in atrial fibrillation burden.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
Unique identifier:
NCT
01219621.
Fourth eu aml Directive: What is Missing? Section 319 patriot Act and the New eu aml Directive
Authors: Canestri Daniele
Published: July 2015

eu Member States are updating their anti-money laundering (aml) regimes by implementing a fourth anti money laundering directive (4th amld). However, an assessment of various aml enforcement regimes reveals that not European, but usa regulations are the most effective. The usa’s aml legislation grants the usa authorities extraterritorial power, which allows them to impose usa requirements on any foreign financial institution that has a correspondent relationship with a usa bank. This long-arm approach is mainly based on Section 319 of the patriot Act. Despite the clear success of Section 319, eu legislators have avoided introducing a similar norm into the latest eu directive. The author analyses why the usa’ effective extraterritorial practice has not been introduced into the 4th amld. Arguing for the adoption of extraterritorial aml practice by the eu, the author then goes on to outline which reforms the eu should introduce if it wishes to follow the path already taken by the usa.
Nemopsis mianzani n. sp. (Hydrozoa, Bougainvilliidae), a new hydromedusa from central Chile
Authors: OLIVEIRA OTTO M. P. , FELIÚ GUILLERMO , PALMA SERGIO
Published: July 2015

The genus Nemopsis, a bougainvillid hydrozoan with a dominant medusa phase, currently includes three species (Nemopsis bachei, N. dofleini and N. hexacanalis), all characterized by the presence of a pair of club-shaped tentacles in the median portion of the marginal bulbs. In this paper, we describe a fourth species, based on the medusa collected off Dichato, central Chilean coast.
Acteonidae, Bullinidae and Ringiculidae (Gastropoda: Heterobranchia) from the Plio-Pleistocene of the Philippines
Authors: HELWERDA RENATE A.
Published: July 2015

Twenty-three species of Acteonidae, Bullinidae and Ringiculidae are documented from the so-called “Cabarruyan” fauna from the Plio-Pleistocene of Pangasinan, the Philippines. There are eleven species of Acteonidae, one species of Bullinidae and eleven species of Ringiculidae. Seven species are described here as new, these are: Bathyacteon valdesi nov. spec., Bullina virgoides nov. spec., Ringicula bella nov. spec., R. circumscripta nov. spec., R. caelestis nov. spec., R. opima nov. spec. and Microglyphis angulata nov. spec.. The presence of Acteonidae and Bullinidae indicates that polychaete worms were also present.
A Three-Dimensional Multivariate Modal Analysis of Atmospheric Predictability with Application to the ECMWF Ensemble
Authors: Žagar Nedjeljka , Buizza Roberto , Tribbia Joseph
Published: July 2015

A new methodology for the analysis of ensemble prediction systems (ENSs) is presented and applied to 1 month (December 2014) of ECMWF operational ensemble forecasts. The method relies on the decomposition of the global three-dimensional wind and geopotential fields onto the normal-mode functions. The ensemble properties are quantified in terms of the 50-member ensemble spread associated with the balanced and inertio-gravity (IG) modes for forecast ranges every 12 h up to 7 days. Ensemble reliability is defined for the balanced and IG modes comparing the ensemble spread with the control analysis in each scale.

Modal analysis shows that initial uncertainties in the ECMWF ENS are largest in the tropical large-scale modes and their spatial distribution is similar to the distribution of the short-range forecast errors. Initially the ensemble spread grows most in the smallest scales and in the synoptic range of the IG modes but the overall growth is dominated by the increase of spread in balanced modes in synoptic and planetary scales in the midlatitudes. During the forecasts, the distribution of spread in the balanced and IG modes grows toward the climatological spread distribution characteristic of the analyses. In the 2-day forecast range, the global IG spread reaches 60% of its asymptotic value while the same percentage of the global balanced spread is reached after 5 days of forecasts. An underdispersiveness of the system is suggested to be associated with the lack of tropical variability, primarily the Kelvin waves.
The Dynamical Influence of Separate Teleconnections from the Pacific and Indian Oceans on the Northern Annular Mode
Authors: Fletcher Christopher G. , Cassou Christophe
Published: July 2015

The northern annular mode (NAM) influences wintertime climate variability in the Northern Hemisphere, and understanding the processes controlling its sign and amplitude is of critical importance. Mounting evidence supports a robust teleconnection between the El Niño–Southern Oscillation (ENSO) and the NAM, while internal variability generated in the tropical Indian Ocean (TIO) may be associated with a NAM response of the opposite sign. This study uses a coupled ocean–atmosphere model to separate the influence on the NAM from teleconnections driven by ENSO and the TIO. In composites constructed using a long preindustrial control integration, increased December–February precipitation in the central/eastern Pacific drives a negative late-winter NAM response. When isolated from ENSO variability, increased precipitation over the western-central TIO drives a strong and persistent positive NAM response throughout the winter. Opposite linear interference of the anomalous wave teleconnections explains most of the opposite-signed planetary wavedriving of the NAM responses. The case with combined ENSO and TIO variability yields cancellation of the wave interference and a weak NAM response. This mechanism is confirmed using experiments where the tropical ocean is nudged separately over the Pacific and TIO to the large-amplitude 1997/98–1998/99 ENSO cycle. The phases of the Rossby wave and NAM responses in these two cases are of opposite sign, providing strong evidence that internal variability over the TIO can induce teleconnections independent of—and with opposite sign to—those associated with ENSO.
Development of a Four-Dimensional Variational Assimilation System for Coastal Data Assimilation around Japan
Authors: Usui Norihisa , Fujii Yosuke , Sakamoto Kei , Kamachi Masafumi
Published: July 2015

The authors have developed an assimilation system toward coastal data assimilation around Japan, which consists of a four-dimensional variational (4DVAR) assimilation scheme with an eddy-resolving model in the western North Pacific (MOVE-4DVAR-WNP) and a fine-resolution coastal model covering the western part of the Japanese coastal region around the Seto Inland Sea (MOVE-Seto). The 4DVAR scheme is developed as a natural extension of the 3DVAR scheme used in the Meteorological Research Institute Multivariate Ocean Variational Estimation (MOVE) system. An initialization scheme of incremental analysis update (IAU) is incorporated into MOVE-4DVAR-WNP to filter out high-frequency noises. During the backward integration of the adjoint model, it works as an incremental digital filtering. MOVE-Seto, which is nested within MOVE-4DVAR-WNP, also employs IAU to initialize the interior of the coastal model using MOVE-4DVAR-WNP analysis fields. The authors conducted an assimilation experiment using MOVE-4DVAR-WNP, and results were compared with an additional experiment using the 3DVAR scheme. The comparison reveals that MOVE-4DVAR-WNP improves mesoscale variability. In particular, short-term variability such as small-scale Kuroshio fluctuations is much enhanced. Using MOVE-Seto and MOVE-4DVAR-WNP, the authors also performed a case study focused on an unusual tide event that occurred at the south coast of Japan in September 2011. MOVE-Seto succeeds in reproducing a significant sea level rise associated with this event, indicating the effectiveness of the newly developed system for coastal sea level variability.
Harmonious Unions and Rebellious Workers
Authors: Anner Mark , Liu Xiangmin
Published: July 2015

The authors examine enterprise-level antecedents of wildcat strikes in Vietnam using a national representative sample of foreign-invested enterprises over the period 2010 to 2012, coding of factory audits, and field research. They predict that these unauthorized, semi-spontaneous work stoppages are more common among unionized workplaces, because the presence of a union in the workplace signals to workers that by engaging in a wildcat strike, they may be able to activate the representation and protection role of official trade unions. That is, workers can in some cases push unions from below to act on their behalf. In addition, wholly foreign-owned enterprises, investments by Asian-owned firms, and manufacturing operations in industrial zones are associated with more strikes than are joint ventures with state-owned and private enterprises, firms owned by Western investors, and firms in higher-value-added activities. Statistical results and field research provide strong support for these predictions. These findings suggest that the role of trade unions in socialist states may be more nuanced than previously assumed. At the same time, they reinforce the observation in the literature that Vietnamese employment relations institutions are unable, in and of themselves, to address worker grievances.
Nonsuicidal self-injury in Indian adolescents: Nonexistent or unacknowledged?
Authors: Aggarwal Shilpa , Berk Michael
Published: July 2015

Nonsuicidal self-injury (NSSI) has been a neglected entity in low- and middle-income countries (LMICs). In this correspondence (letter to the editor), authors are advocating for greater research in this area in LMICs as it will help to compare and contrast prevalence rates of NSSI in these countries with high-income countries (HICs), identify context-specific risk and protective factors to better understand the pathophysiology of NSSI and devise context-specific interventions resulting in improvement in adolescent mental health worldwide.
A review of garment ventilation strategies for structural firefighter protective clothing
Authors: McQuerry Meredith , Den Hartog Emiel , Barker Roger , Ross Kevin
Published: July 2015

The purpose of this review article is to evaluate ventilation, within protective clothing, for its benefit towards heat loss. Literature from ventilation studies in the sports apparel, outdoor clothing, military, chemical, and firefighter protection industries will be examined for future research opportunities. Challenges to ventilation such as garment placement, protection, wearability, and durability will be discussed in the context of turnout suits. Ventilation designs will be considered for further evaluation in structural firefighter turnout garments. This article serves as the first comprehensive review of ventilation literature for structural firefighter turnout ensembles. Researchers, technologists, and functional apparel designers may all benefit from such a review. The value of ventilation and its potential contribution to current firefighter turnout research will be discussed.
Psychometric Evaluation of the Level of Service/Case Management Inventory Among Australian Offenders Completing Community-Based Sentences
Authors: Gordon Heidi , Kelty Sally F. , Julian Roberta
Published: July 2015

Risk assessment inventories play a significant role in predicting recidivism risk and informing parole and community supervision orders. This article examines the effectiveness of the Level of Service/Case Management Inventory (LS/CMI) in a study of Australian offenders completing community-based sentences. The study aimed to identify the internal reliability and the factor structure of the LS/CMI. The results indicated that the LS/CMI total score achieved excellent internal reliability. There is concern regarding the capacity for the subscales to function independently. A factor analysis determined a two-factor solution at a subscale level, whereas a more diverse factor solution was obtained at an item level. The LS/CMI was determined to be predictive of recidivism, but this was a weak effect. The results indicate that the LS/CMI as it is currently used in this population may not be an appropriate assessment tool, requiring further research before an international risk assessment is adopted in Australian jurisdictions.
The scholarly practitioner
Authors: Godwin Marcia L , Meek Jack W
Published: July 2015

This article outlines how Master of Public Administration (MPA) and Doctor of Public Administration (DPA) programs from one university in the United States approach the integration of theory, research, and practice. The article reviews the historic missions of US public administration programs that focus on the development of public service professionals and specialized practitioners. Next, we share how the MPA program integrates theory and research with practice in the development of civic professionals. Examples from the MPA program are shown in a taxonomy with illustrative examples. This article also contrasts the MPA with the DPA program that follows a scholarly practitioner model. Rather than exclusively following a traditional theory-to-practice model, practice-to-theory and more experiential research projects are critical to the development of graduate public administration students working in complex environments. More student-centric and student-initiated approaches provide more opportunities for student engagement and also are aligned with emerging pedagogical models.
Relevance of Goodwill Impairments to Cash Flow Prediction and Forecasting
Authors: Bostwick Eric D. , Krieger Kevin , Lambert Sherwood Lane
Published: July 2015

This study examines the contribution of goodwill impairment information to the prediction and forecasting of future operating cash flows. Extending the framework of Barth, Cram, and Nelson, we find that explicitly including goodwill impairments incrementally improves 1-year-ahead cash flow prediction and forecasting. Improved cash flow forecasting is present over the entire 2001-2009 study period as well as for each year within the study window. In addition, goodwill impairments retain their significance and predictive power when other non-recurring charges (e.g., restructuring, asset write-downs, and merger and acquisition costs) are added to the model, both individually and aggregately, and when market-related information (i.e., change in market capitalization) is included in the model. While these findings are validated by in-sample prediction techniques, this study is also one of only a few studies to investigate the incremental, out-of-sample predictive power of non-current accruals on reported (as opposed to computed) operating cash flows. Analysts, investors, creditors, and others interested in future cash flows should separately consider goodwill impairment information, when available, to improve the accuracy of cash flow prediction and forecasting.
Political and economic accountability in a delegative democracy
Authors: Tusalem Rollin F
Published: July 2015

Recently, economic accountability theory as a means by which to hold political leaders accountable in the industrialized world has been generalized in transitional democracies. The theory advances how mass publics in young democracies evaluate and assess the performance of chief executives based on sociotropic or pocketbook economic evaluations and the occurrence of pivotal political events. The study finds that self-placement on poverty among Filipinos and primordial assessments of hunger are predictors of presidential approval. Pivotal political events involving attempted coups, corrupt practices and executive level malfeasance are not likely to affect presidential approval ratings over time. Furthermore, changes in the national economy have no association with Philippine presidential approval ratings from 1986–2009. The results of the study suggest that political and economic theories of accountability as applied to the developing world should be reassessed by taking into account the non-institutionalization of party systems, strong executive structures, and the politics of personalism, patronage and patrimonialism.
Primary diffuse pleural rhabdomyosarcoma in an adult patient
Authors: Koksal Deniz , Ibrahimov Ferhad , Bugdayci Meral , Gedikoglu Gokhan , Emri Salih
Published: July 2015

Rhabdomyosarcoma is an aggressive malignant tumor of childhood, originating from immature cells that are destinated to form striated skeletal muscle. It usually arises in the head and neck or the extremities. Primary diffuse pleural rhabdomyosarcoma is exceptionally rare. Herein we report a case of primary diffuse pleural rhabdomyosarcoma in a 48-year-old man. The diagnosis was confimed by percutaneous pleural biopsy. Chemotherapy (cisplatin, ifosfamide, adriamycin, vincristine) was initiated due to the large volume of the tumor. After 3 months, computed tomography of the thorax showed stable radiological findings.
Thyroid carcinoma showing thymus-like differentiation with tracheal invasion
Authors: Wu Ming-Ho , Wu Han-Yun
Published: July 2015

We describe a case of thyroid carcinoma showing thymus-like differentiation with tracheal invasion. The malignant tumor was managed by refined spiral tracheoplasty after tangential resection of the trachea. At 8 months after the surgery, computed tomography and bronchoscopy showed no tumor recurrence or tracheal stenosis.
Cough-induced rib fractures
Authors: Sano Atsushi , Tashiro Ken , Fukuda Tsutomu
Published: July 2015

Background

Occasionally, patients who complain of chest pain after the onset of coughing are diagnosed with rib fractures. We investigated the characteristics of cough-induced rib fractures.

Methods

Between April 2008 and December 2013, 17 patients were referred to our hospital with chest pain after the onset of coughing. Rib radiography was performed, focusing on the location of the chest pain. When the patient had other signs and symptoms such as fever or persistent cough, computed tomography of the chest was carried out. We analyzed the data retrospectively.

Results

Rib fractures were found in 14 of the 17 patients. The age of the patients ranged from 14 to 86 years (median 39.5 years). Ten patients were female and 4 were male. Three patients had chronic lung disease. There was a single rib fracture in 9 patients, and 5 had two or more fractures. The middle and lower ribs were the most commonly involved; the 10th rib was fractured most frequently.

Conclusions

Cough-induced rib fractures occur in every age group regardless of the presence or absence of underlying disease. Since rib fractures often occur in the lower and middle ribs, rib radiography is useful for diagnosis.
Residential Estate Valuation Index (REVI): A Consumer Perspective
Authors: Sharma Bramh Dev
Published: July 2015

Motivation/Problem:

Real estate has emerged as one of the most profitable investing options in Indian economy, and its valuation plays an important role in the process. Valuations of real estate are a debatable issue due to lack of research and support knowledge available to the stakeholders and market makers, namely, owners, such as sellers, buyers, brokers and valuers, and lenders, such as bankers and financial institutions. In this article, the author seeks to develop a residential estate valuation index, a consumer perspective.

Methodology:

In the first stage the author has identified consumer-centric factors of residential valuation from literature review and grounded theory. In the second stage SPSS & MS Excel techniques are used to find out consumer-driven weights of each factor and to subsequently develop an index matrix.

Output:

A residential estate valuation index has been developed. This study attempts to develop a residential estate valuation index for measuring the consumer behaviour with residential estate, residential estate seen as habitat that is an output/product architecture. This index will be helpful for stakeholders, market makers, sellers, buyers, brokers, valuers, bankers and financial institutions in high-involvement decision-making.
Influence of Experiential Marketing on Customer Purchase Intention: A Study of Passenger Car Market
Authors: Khan Imran , Rahman Zillur
Published: July 2015

This study attempts to explore and interrogate a potential strategy by developing relationship of experiential marketing with customer purchase intention in competitive passenger car market. This study scrutinizes the importance of the experiential marketing approach to the Indian passenger car market from the customer’s perspective. Mixed-method research design has been preferred here, an approach increasingly used in social science research. This research design deals with exploratory analysis, followed by quantitative analysis techniques. The interpretive basis for the evaluation has been provided through multiple regression analysis. This study shows that all the structural experiential modules are affecting the customer purchase intention in the automobile (passenger car) market, where feel, think and sense experiences have a strong influence on customer purchase intention. This research is particularly important in determining the effect of experiential marketing on the customer purchase intention with respect to passenger car market. Considering the current economic slowdown where Indian automobile industry is facing a slowdown in sales, the findings of the study can be useful for passenger car companies in developing better marketing strategies.