bluuebunny/crossref_metadata_2025 huggingface dataset:
Next-Generation Sequencing in the Clinical Setting Clarifies Patient Characteristics and Potential Actionability
Authors: Bieg-Bourne Cheyennedra C. , Millis Sherri Z. , Piccioni David E. , Fanta Paul T. , Goldberg Michael E. , Chmielecki Juliann , Parker Barbara A. , Kurzrock Razelle
Published: September 2017

Enhancements in clinical-grade next-generation sequencing (NGS) have fueled the advancement of precision medicine in the clinical oncology field. Here, we survey the molecular profiles of 1,113 patients with diverse malignancies who successfully underwent clinical-grade NGS (236–404 genes) in an academic tertiary cancer center. Among the individual tumors examined, the majority showed at least one detectable alteration (97.2%). Among 2,045 molecular aberrations was the involvement of 302 distinct genes. The most commonly altered genes were TP53 (47.0%), CDKN2A (18.0%), TERT (17.0%), and KRAS (16.0%), and the majority of patients had tumors that harbored multiple alterations. Tumors displayed a median of four alterations (range, 0–29). Most individuals had at least one potentially actionable alteration (94.7%), with the median number of potentially actionable alterations per patient being 2 (range, 0–13). A total of 1,048 (94.2%) patients exhibited a unique molecular profile, with either genes altered or loci within the gene(s) altered being distinct. Approximately 13% of patients displayed a genomic profile identical to at least one other patient; although genes altered were the same, the affected loci may have differed. Overall, our results underscore the complex heterogeneity of malignancies and argue that customized combination therapies will be essential to optimize cancer treatment regimens. Cancer Res; 77(22); 6313–20. ©2017 AACR.
Tumor Heterogeneity Predicts Metastatic Potential in Colorectal Cancer
Authors: Joung Je-Gun , Oh Bo Young , Hong Hye Kyung , Al-Khalidi Hisham , Al-Alem Faisal , Lee Hae-Ock , Bae Joon Seol , Kim Jinho , Cha Hong-Ui , Alotaibi Maram , Cho Yong Beom , Hassanain Mazen , Park Woong-Yang , Lee Woo Yong
Published: September 2017

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis.

Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated.

Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors.

Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209–16. ©2017 AACR.
Integrated Analysis Reveals Tubal- and Ovarian-Originated Serous Ovarian Cancer and Predicts Differential Therapeutic Responses
Authors: Hao Dapeng , Li Jingjing , Jia Shanshan , Meng Yuan , Zhang Chao , Wang Li , Di Li-jun
Published: September 2017

Purpose: The relative importance of fallopian tube (FT) compared with ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs.

Experimental Design: A collection of transcriptome data of 80 FTs, 89 OSEs, and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors. A molecular signature was developed for identifying tissue origin of SOC and then was used to reevaluate the prognostic genes and therapeutic biomarkers of SOC of different tissue origins. IHC staining of tissue array and functional experiments on a panel of ovarian cancer cell lines were used to further validate the key findings.

Results: The expression patterns of tissue-specific genes, prognostic genes, and molecular markers all support a dualistic tissue origin of SOC, from either FT or OSE. A molecular signature was established to identify the tissue identity of SOCs. Surprisingly, the signature showed a strong association with overall survival (OSE-like vs. FT-like, HR = 4.16; 95% CI, 2.67–6.48; P < 10−9). The pharmacogenomic approach revealed AXL to be a therapeutic target of the aggressive OSE-derived SOC.

Conclusions: SOC has two subtypes originated from either FT or OSE, which show different clinical and pathologic features. Clin Cancer Res; 23(23); 7400–11. ©2017 AACR.
Phospholipase D1 Inhibition Linked to Upregulation of ICAT Blocks Colorectal Cancer Growth Hyperactivated by Wnt/β-Catenin and PI3K/Akt Signaling
Authors: Kang Dong Woo , Lee Bo Hui , Suh Young-Ah , Choi Yong-Seok , Jang Se Jin , Kim Yong Man , Choi Kang-Yell , Min Do Sik
Published: September 2017

Purpose: Dysregulated expression of PLD1 has emerged as a hallmark feature of colorectal cancer, which remains a major cause of mortality worldwide. Aberrant activation of Wnt/β-catenin signaling is a critical event in the development of colorectal cancer. Here, we investigated molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways via inhibitor of β-catenin and T-cell factor (ICAT), a negative regulator of Wnt/β-catenin signaling. We also explored the effect of PLD1 inhibition on growth of colorectal cancer hyperactivated by Wnt/β-catenin and PI3K/Akt signaling.

Experimental Design: Expression of ICAT via targeting of PLD1 was assessed in vivo in ApcMin/+ mice, an AOM/DSS model, and in vitro using various colorectal cancer cells. The relationship between ICAT/PLD1 expression and prognostic survival value of 153 colorectal cancer patients was examined. The therapeutic efficacy of PLD1 inhibitor was determined using a patient-derived xenograft model carrying APC and PI3K mutations.

Results: PLD1 promoted the Wnt/β-catenin signaling pathway by selectively downregulating ICAT via the PI3K/Akt-TopBP1-E2F1 signaling pathways. Low PLD1 expression and high ICAT expression were significantly associated with increased survival in colorectal cancer patients and vice versa. Furthermore, PLD1 inhibition suppressed growth of colorectal cancer activated by the Wnt/β-catenin and PI3K signaling pathways.

Conclusions: These results suggest that PLD1 linked to ICAT mediates molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways and thus could be proposed as a novel colorectal cancer prognostic biomarker. These results may assist in the clinical development of a PLD1 inhibitor for treatment of colorectal cancer patients carrying APC and PI3KCA mutations. PLD1, a nodal modifier, acts as a potential therapeutic target for the treatment of colorectal cancer hyperactivated by the Wnt/β-catenin and PI3K/Akt signaling pathways. Clin Cancer Res; 23(23); 7340–50. ©2017 AACR.
CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma
Authors: Avril Tony , Etcheverry Amandine , Pineau Raphaël , Obacz Joanna , Jegou Gwénaële , Jouan Florence , Le Reste Pierre-Jean , Hatami Masumeh , Colen Rivka R. , Carlson Brett L. , Decker Paul A. , Sarkaria Jann N. , Vauléon Elodie , Chiforeanu Dan Cristian , Clavreul Anne , Mosser Jean , Chevet Eric , Quillien Véronique
Published: September 2017

Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.

Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.

Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo. Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90high primary GSC lines.

Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90high GBM patients. Clin Cancer Res; 23(23); 7360–74. ©2017 AACR.
A Novel Breast Cancer Index for Prediction of Distant Recurrence in HR+ Early-Stage Breast Cancer with One to Three Positive Nodes
Authors: Zhang Yi , Schroeder Brock E. , Jerevall Piiha-Lotta , Ly Amy , Nolan Hannah , Schnabel Catherine A. , Sgroi Dennis C.
Published: September 2017

Purpose: The study objective was to characterize the prognostic performance of a novel Breast Cancer Index model (BCIN+), an integration of BCI gene expression, tumor size, and grade, specifically developed for assessment of distant recurrence (DR) risk in HR+ breast cancer patients with one to three positive lymph nodes (pN1).

Experimental Design: Analysis was conducted in a well-annotated retrospective series of pN1 patients (N = 402) treated with adjuvant endocrine therapy with or without chemotherapy using a prespecified model. The primary endpoint was time-to-DR. Results were determined blinded to clinical outcome. Kaplan-Meier estimates of overall (0–15 years) and late (≥5 years) DR, HRs, and 95% confidence interval (CIs) were estimated. Likelihood ratio statistics assessed relative contributions of prognostic information.

Results: BCIN+ classified 81 patients (20%) as low risk with a 15-year DR rate of 1.3% (95% CI, 0.0%–3.7%) versus 321 patients as high risk with a DR rate of 29.0% (95% CI, 23.2%–34.4%). In patients DR-free for ≥5 years (n = 349), the late DR rate was 1.3% (95% CI, 0.0%–3.7%) and 16.1% (95% CI, 10.6%–21.3%) in low- and high-risk groups, respectively. BCI gene expression alone was significantly prognostic (ΔLR-χ2 = 20.12; P < 0.0001). Addition of tumor size (ΔLR-χ2 = 13.29, P = 0.0003) and grade (ΔLR-χ2 = 12.72; P = 0.0004) significantly improved prognostic performance. BCI added significant prognostic information to tumor size (ΔLR-χ2 = 17.55; P < 0.0001); addition to tumor grade was incremental (ΔLR-χ2 = 2.38; P = 0.1) with considerable overlap between prognostic values (ΔLR-χ2 = 17.74).

Conclusions: The integrated BCIN+ identified 20% of pN1 patients with limited risk of recurrence over 15 years, in whom extended endocrine treatment may be spared. Ongoing studies will characterize combined clinical-genomic risk assessment in node-positive patients. Clin Cancer Res; 23(23); 7217–24. ©2017 AACR.
A Chemical Modulator of p53 Transactivation that Acts as a Radioprotective Agonist
Authors: Morita Akinori , Takahashi Ippei , Sasatani Megumi , Aoki Shin , Wang Bing , Ariyasu Shinya , Tanaka Kaoru , Yamaguchi Tetsuji , Sawa Akiko , Nishi Yurie , Teraoka Tatsuro , Ujita Shohei , Kawate Yosuke , Yanagawa Chihiro , Tanimoto Keiji , Enomoto Atsushi , Nenoi Mitsuru , Kamiya Kenji , Nagata Yasushi , Hosoi Yoshio , Inaba Toshiya
Published: September 2017

Inhibiting p53-dependent apoptosis by inhibitors of p53 is an effective strategy for preventing radiation-induced damage in hematopoietic lineages, while p53 and p21 also play radioprotective roles in the gastrointestinal epithelium. We previously identified some zinc(II) chelators, including 8-quinolinol derivatives, that suppress apoptosis in attempts to discover compounds that target the zinc-binding site in p53. We found that 5-chloro-8-quinolinol (5CHQ) has a unique p53-modulating activity that shifts its transactivation from proapoptotic to protective responses, including enhancing p21 induction and suppressing PUMA induction. This p53-modulating activity also influenced p53 and p53-target gene expression in unirradiated cells without inducing DNA damage. The specificity of 5CHQ for p53 and p21 was demonstrated by silencing the expression of each protein. These effects seem to be attributable to the sequence-specific alteration of p53 DNA-binding, as evaluated by chromatin immunoprecipitation and electrophoretic mobility shift assays. In addition, 5-chloro-8-methoxyquinoline itself had no antiapoptotic activity, indicating that the hydroxyl group at the 8-position is required for its antiapoptotic activity. We applied this remarkable agonistic activity to protecting the hematopoietic and gastrointestinal system in mouse irradiation models. The dose reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. 5CHQ effectively protected mouse epithelial stem cells from a lethal dose of abdominal irradiation. Furthermore, the specificity of 5CHQ for p53 in reducing the lethality induced by abdominal irradiation was revealed in Trp53-KO mice. These results indicate that the pharmacologic upregulation of radioprotective p53 target genes is an effective strategy for addressing the gastrointestinal syndrome. Mol Cancer Ther; 17(2); 432–42. ©2017 AACR.

See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”
Targeting Phosphatidylserine with Calcium-Dependent Protein–Drug Conjugates for the Treatment of Cancer
Authors: Li Ran , Chiguru Srinivas , Li Li , Kim Dongyoung , Velmurugan Ramraj , Kim David , Devanaboyina Siva Charan , Tian Hong , Schroit Alan , Mason Ralph P. , Ober Raimund J. , Ward E. Sally
Published: September 2017

In response to cellular stress, phosphatidylserine is exposed on the outer membrane leaflet of tumor blood vessels and cancer cells, motivating the development of phosphatidylserine-specific therapies. The generation of drug-conjugated phosphatidylserine-targeting agents represents an unexplored therapeutic approach, for which antitumor effects are critically dependent on efficient internalization and lysosomal delivery of the cytotoxic drug. In the current study, we have generated phosphatidylserine-targeting agents by fusing phosphatidylserine-binding domains to a human IgG1-derived Fc fragment. The tumor localization and pharmacokinetics of several phosphatidylserine-specific Fc fusions have been analyzed in mice and demonstrate that Fc-Syt1, a fusion containing the synaptotagmin 1 C2A domain, effectively targets tumor tissue. Conjugation of Fc-Syt1 to the cytotoxic drug monomethyl auristatin E results in a protein–drug conjugate (PDC) that is internalized into target cells and, due to the Ca2+ dependence of phosphatidylserine binding, dissociates from phosphatidylserine in early endosomes. The released PDC is efficiently delivered to lysosomes and has potent antitumor effects in mouse xenograft tumor models. Interestingly, although an engineered, tetravalent Fc-Syt1 fusion shows increased binding to target cells, this higher avidity variant demonstrates reduced persistence and therapeutic effects compared with bivalent Fc-Syt1. Collectively, these studies show that finely tuned, Ca2+-switched phosphatidylserine-targeting agents can be therapeutically efficacious. Mol Cancer Ther; 17(1); 169–82. ©2017 AACR.
Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib)
Authors: Germann Ursula A. , Furey Brinley F. , Markland William , Hoover Russell R. , Aronov Alex M. , Roix Jeffrey J. , Hale Michael , Boucher Diane M. , Sorrell David A. , Martinez-Botella Gabriel , Fitzgibbon Matthew , Shapiro Paul , Wick Michael J. , Samadani Ramin , Meshaw Kathryn , Groover Anna , DeCrescenzo Gary , Namchuk Mark , Emery Caroline M. , Saha Saurabh , Welsch Dean J.
Published: September 2017

Aberrant activation of signaling through the RAS–RAF–MEK–ERK (MAPK) pathway is implicated in numerous cancers, making it an attractive therapeutic target. Although BRAF and MEK-targeted combination therapy has demonstrated significant benefit beyond single-agent options, the majority of patients develop resistance and disease progression after approximately 12 months. Reactivation of ERK signaling is a common driver of resistance in this setting. Here we report the discovery of BVD-523 (ulixertinib), a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity. In vitro BVD-523 treatment resulted in reduced proliferation and enhanced caspase activity in sensitive cells. Interestingly, BVD-523 inhibited phosphorylation of target substrates despite increased phosphorylation of ERK1/2. In in vivo xenograft studies, BVD-523 showed dose-dependent growth inhibition and tumor regression. BVD-523 yielded synergistic antiproliferative effects in a BRAFV600E-mutant melanoma cell line xenograft model when used in combination with BRAF inhibition. Antitumor activity was also demonstrated in in vitro and in vivo models of acquired resistance to single-agent and combination BRAF/MEK–targeted therapy. On the basis of these promising results, these studies demonstrate BVD-523 holds promise as a treatment for ERK-dependent cancers, including those whose tumors have acquired resistance to other treatments targeting upstream nodes of the MAPK pathway. Assessment of BVD-523 in clinical trials is underway (NCT01781429, NCT02296242, and NCT02608229). Mol Cancer Ther; 16(11); 2351–63. ©2017 AACR.
Hemodynamic Profile of Patients With Heart Failure and Preserved Ejection Fraction Vary by Age
Authors: Nanayakkara Shane , Haykowsky Mark , Mariani Justin , Van Empel Vanessa , Maeder Micha T. , Vizi Donna , Kaye David M.
Published: September 2017

Background

Patients with heart failure with preserved ejection fraction (
HFpEF
) exhibit a range of cardiovascular phenotypic profiles modified by several common comorbidities. In particular, patients with HFpEF tend to be older; however, it is unclear whether the effects of cardiovascular aging per se modify the expression of
HFpEF
. We therefore sought to investigate the interaction between age and physiologic profile in patients with
HFpEF
.

Methods and Results

We assessed the hemodynamic and metabolic profile of 40 patients with
HFpEF
. Patients underwent right heart catheterization at rest and during supine cycle ergometry, and were segregated into 2 groups by the median age of the cohort. Older patients with HFpEF demonstrated reduced resting cardiac output (4.8±1.2 L/min versus 5.7±1.1 L/min). With exercise, older patients demonstrated a marked rise in arteriovenous oxygen content difference (10.8±1.8 versus 7.9±2.4 mL,
P
≤0.001), driven by enhanced oxygen extraction. There was no significant difference in peak pulmonary capillary wedge pressure (30±7 mm Hg versus 27±6,
P
=0.135), including when indexed to workload (pulmonary capillary wedge pressure/W, 0.88 mm Hg/W versus 0.92;
P
=0.83).

Conclusions

Older patients with HFpEF display a different physiological phenotype compared with younger patients, with enhanced oxygen extraction and lower increment in cardiac output to increase oxygen consumption from rest to peak supine exercise. This finding highlights the importance in considering age when considering therapeutic options in patients with
HFpEF
.
Trends in Use of Biomarker Protocols for the Evaluation of Possible Myocardial Infarction
Authors: Hachey Brian J. , Kontos Michael C. , Newby L. Kristin , Christenson Robert H. , Peacock W. Frank , Brewer Katherine C. , McCord James
Published: September 2017

Background

Various combinations of creatine kinase‐MB, myoglobin, and cardiac troponin I or T (cTnI/cTnT) have been used to evaluate patients with suspected acute coronary syndromes. The current recommendation is to use the 99th percentile of cTnI/cTnT as the sole marker for diagnosis of acute myocardial infarction.

Methods and Results

We retrospectively analyzed cardiac marker protocols collected from 824 US hospitals undergoing Chest Pain Center Accreditation through the Society of Cardiovascular Patient Care from 2009 to 2014. Data were obtained by a self‐reported survey that addressed cardiac marker(s), sampling time periods, and cut points used for evaluation of suspected acute myocardial infarction. The combination of cTnI or cTnT with creatine kinase‐MB was the most commonly used biomarker strategy. Use of cTnI or cTnT as the sole marker increased over time (14–37%;
P
<0.0001), as did use of the 99th percentile cut point for cTnI/cTnT (30–60%;
P
<0.0001).

Conclusion

There is considerable variation in cardiac marker testing strategies used in US hospitals for evaluation of suspected acute myocardial infarction. Although increasing, 24% of hospitals used a cTn alone strategy, and only 49% used cTn at the recommended 99th percentile cut point. This has important implications for the diagnosis and treatment of patients with acute myocardial infarction.
Trends in Racial/Ethnic Disparities in Cardiovascular Health Among US Adults From 1999–2012
Authors: Pool Lindsay R. , Ning Hongyan , Lloyd‐Jones Donald M. , Allen Norrina B.
Published: September 2017

Background

In the United States, there are persistent racial and ethnic disparities in cardiovascular disease morbidity and mortality. National efforts have focused on reducing these disparities; however, little is known about the long‐term trends in racial/ethnic disparities in cardiovascular health (
CVH
).

Methods and Results

We included 11 285 adults aged ≥20 years from the National Health and Nutrition Examination Surveys survey cycles 1999/2000 through 2011/2012.
CVH
includes 7 health factors and behaviors—diet, physical activity, smoking status, body mass index, blood pressure, blood glucose, and total cholesterol—each scored as ideal (2 points), intermediate (1 point), or poor (0 points). Overall
CVH
is a summation of these scores (range, 0–14) points. Age‐adjusted mean
CVH
scores were calculated by race/ethnicity (non‐Hispanic black, non‐Hispanic white, or Mexican American) and sex for each survey cycle. Non‐Hispanic black women had significantly lower mean
CVH
scores as compared with non‐Hispanic white women at each survey cycle (difference=0.93;
P
=0.001 in 2011/2012) and Mexican‐American women had significantly lower mean score as compared with non‐Hispanic white women at almost all survey cycles (difference=0.71;
P
=0.02 in 2011/2012). Differences between racial/ethnic groups were smaller for men and were mostly nonsignificant.

Conclusions

From 1999/2000 to 2011/2012, there were enduring disparities in
CVH
for non‐Hispanic black and Mexican‐American women as compared with non‐Hispanic white women. Disparities that were present in 1999/2000 were present in 2011/2012, though no racial/ethnic differences became more pronounced over time. These findings provide
US
nationally representative data to evaluate health factors and behaviors of particular concern regarding racial/ethnic disparities in cardiovascular health.
Kidney Disease Measures and Left Ventricular Structure and Function: The Atherosclerosis Risk in Communities Study
Authors: Matsushita Kunihiro , Kwak Lucia , Sang Yingying , Ballew Shoshana H. , Skali Hicham , Shah Amil M. , Coresh Josef , Solomon Scott
Published: September 2017

Background

Heart failure is one of the most important complications of chronic kidney disease (CKD). However, few studies comprehensively investigated left ventricular (LV) structure and function in relation to 2 key CKD measures, estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR).

Methods and Results

Among 4175 ARIC (Atherosclerosis Risk in Communities) participants (aged 66–90 years during 2011–2013), we quantified the association of eGFR and ACR with echocardiogram parameters of LV mass, size, systolic function, and diastolic function. Adjusting for demographic variables, both CKD measures were significantly associated with most echocardiogram parameters. Additionally accounting for other potential confounders, we observed significantly higher LV mass index according to reduced eGFR (82.3 [95% confidence interval (CI), 77.6–87.0] g/m
2
for eGFR <30 mL/min per 1.73 m
2
, 80.9 [95% CI, 77.3–84.6] g/m
2
for eGFR 30–44 mL/min per 1.73 m
2
, and 80.1 [95% CI, 76.7–83.5] g/m
2
for eGFR 45–59 mL/min per 1.73 m
2
compared with 78.7 [95% CI, 75.3–82.1] g/m
2
for eGFR 75–89 mL/min per 1.73 m
2
; trend
P
<0.001). Regarding LV size and function, significant differences were observed for some parameters, particularly at eGFR <30 mL/min per 1.73 m
2
. For ACR, the associations remained significant for most parameters (eg, LV mass index, 91.5 [95% CI, 86.6–96.5] g/m
2
for ACR ≥300 mg/g and 82.9 [95% CI, 79.4–86.3] g/m
2
for ACR 30–299 mg/g compared with 77.7 [95% CI, 74.4–81.1] g/m
2
for ACR <10 mg/g [trend
P
<0.001]; left arterial volume index, 24.9 [95% CI, 22.9–26.8] and 24.7 [95% CI, 23.4–26.1] mL/m
2
compared with 23.4 [95% CI, 22.1–24.7] mL/m
2
, respectively [trend
P
=0.010]). Dichotomizing echo parameters with clinical thresholds, the stronger relationships of ACR over eGFR were further evident.

Conclusions

LV mass was related to both CKD measures, whereas LV size and function were robustly associated with albuminuria. These results have implications for pathophysiological processes behind cardiorenal syndrome and targeted cardiac assessment in patients with CKD.
Clinical Characteristics and Management of Coronary Artery Perforations: A Single‐Center 11‐Year Experience and Practical Overview
Authors: Lemmert Miguel E. , van Bommel Rutger J. , Diletti Roberto , Wilschut Jeroen M. , de Jaegere Peter P. , Zijlstra F. , Daemen Joost , Van Mieghem Nicolas M.
Published: September 2017

Background

Coronary artery perforation (CAP) is a potentially lethal complication of percutaneous coronary intervention. We report on the incidence, clinical characteristics, and management of iatrogenic coronary perforations based on an 11‐year single‐center experience.

Methods and Results

From February 9, 2005, through November 20, 2016, 150 CAP cases were identified from our percutaneous coronary intervention database of 21 212 procedures (0.71%). Mean age of CAP patients was 66±11 years, and 62.7% were male. Treated lesion type was B2/C in 94.6%, and 31.3% were chronic total occlusions. Nonworkhorse guidewires were applied in 74.3%. CAP types were Ellis type I in 2.9%, Ellis type II in 40.4%, Ellis type III in 54.8%, and Ellis type III cavity spilling in 1.9%. CAP treatment was conservative (including prolonged balloon inflation) in 73.3%. Covered stents, coiling, and fat embolization were used in 24.0%, 0.7%, and 2.0%, respectively. Pericardiocentesis for tamponade was required for 72 patients (48.0%), of whom 28 were initially unrecognized. Twelve patients (12.7%) required emergency cardiac surgery to alleviate tamponade. Periprocedural myocardial infarction occurred in 34.0%, and in‐hospital all‐cause mortality was 8.0%. All‐cause mortality accrued to 10.7% at 30 days and 17.8% at 1 year.

Conclusions

CAP is a rare complication of percutaneous coronary intervention, but morbidity and mortality are considerable. Early recognition and adequate management are of paramount importance.
Safety Outcomes After Percutaneous Transcatheter Closure of Patent Foramen Ovale
Authors: Merkler Alexander E. , Gialdini Gino , Yaghi Shadi , Okin Peter M. , Iadecola Costantino , Navi Babak B. , Kamel Hooman
Published: September 2017

Background and Purpose—

We sought to evaluate the real-world rate of safety outcomes after patent foramen ovale (PFO) closure in patients with ischemic stroke or transient ischemic attack (TIA).

Methods—

We performed a retrospective cohort study using administrative claims data on all hospitalizations from 2005 to 2013 in New York, California, and Florida. Using
International Classification of Diseases, Ninth Revision, Clinical Modification
codes, we identified patients who underwent percutaneous transcatheter PFO closure within 1 year of ischemic stroke or TIA. Our outcome was an adverse event occurring during the hospitalization for PFO closure, defined as in prior studies as atrial fibrillation or flutter, cardiac tamponade, pneumothorax, hemothorax, a vascular access complication, or death. Crude rates were reported with exact confidence intervals.

Results—

We identified 1887 patients who underwent PFO closure after ischemic stroke or TIA. The rate of any adverse outcome during the hospitalization for PFO closure was 7.0% (95% confidence interval [CI], 5.9%–8.2%). Rates of adverse outcomes varied by age and type of preceding cerebrovascular event. In patients >60 years of age, the rate of adverse outcomes was 10.9% (95% CI, 8.6%–13.6%) versus 4.9% (95% CI, 3.8%–6.3%) in patients ≤60 years of age. The rate of adverse outcomes was 9.9% (95% CI, 7.3%–12.5%) in patients with preceding ischemic stroke versus 5.9% (95% CI, 4.7%–7.1%) after TIA.

Conclusions—

Approximately 1 in 14 patients who underwent percutaneous transcatheter PFO closure after ischemic stroke or TIA experienced a serious periprocedural adverse outcome or death. The risk of adverse outcomes was highest in older patients and in those with preceding ischemic stroke.
No Asylum for the Innocent: Gendered Representations of Salvadoran Refugees in the 1980s
Authors: De La Cruz Rachael
Published: September 2017

During the 1980s, El Salvador was engaged in a brutal civil war; massacres, torture, and rape pervaded the countryside. This social and economic upheaval created approximately 1.5 million refugees and internally displaced persons throughout Central and North America. Gender is a critical yet understudied aspect of this mass displacement. I analyze humanitarian publications and government documents to examine the discursive gendering of Salvadoran refugees on the international stage. I argue that U.S. activists portrayed Salvadorans as feminized civilian victims in need of rescue by the paternalistic United States to change public opinion of the Salvadoran Civil War and its refugees. These gendered and infantilized constructions belie the reality that the vast majority of Salvadoran refugees to the United States were men of military age. I examine the Salvadoran refugee from a new perspective that foregrounds gender as a category of analysis.
Crime and Ethnic Diversity: Cross-Country Evidence
Authors: Awaworyi Churchill Sefa , Laryea Emmanuel
Published: September 2017

Is the level of crime in countries explained by ethnic diversity? This study attempts to answer this question by providing empirical evidence that examines the effects of ethnic and linguistic fractionalization on various measures of crime rates, including prosecution and conviction rates. Drawing on data across 78 countries, our study addresses the endogenous nature of the association between ethnic diversity and crime. Our empirical findings show, rather unexpectedly and counterintuitively, that higher levels of ethnic and linguistic diversity tend to aid in the reduction of crime rates and, consequently, lead to lower prosecution and conviction rates. We advance possible reasons for this unexpected result and outline some policy recommendations.
City Children’s Nature Knowledge and Contact: It Is Not Just About Biodiversity Provision
Authors: Freeman Claire , Stein Aviva , Hand Kathryn , van Heezik Yolanda
Published: September 2017

Much attention has been directed at the perceived decline in city children’s contact with nature. We used a child-centric approach to assess neighborhood nature knowledge in 187 children aged 9 to 11 years, from different socioeconomic and ethnic groups in three New Zealand cities. We evaluated the relative importance of social (independence, gender, social connections, deprivation, age) and environmental factors (biodiversity) in explaining variation in knowledge at a scale relevant to each child’s independent movements. Our biodiversity evaluation reflected the natural dimensions of the habitats where children interacted with nature. Generalized linear modeling identified ethnicity as having the strongest association with nature knowledge. Within each ethnic group, social factors were most important (independence, social connections, deprivation) except for Pākehā/NZ European children, where local biodiversity was most important. Enhancing biodiversity values of private green spaces (yards) would be effective in facilitating opportunities to experience nature, which is fundamental to supporting nature contact.
Medicines education at home – A case study in Finland
Authors: Hokkanen Johanna , Elorinne Anna-Liisa , Hämeen-Anttila Katri , Keinonen Tuula
Published: September 2017

Background:

Educating children about medicines and medicine use is part of health education and is often seen as parents’ responsibility. However, to date, little research has been conducted on medicines education as provided in the home.

Objective:

To explore (1) parents’ attitudes towards medicines, (2) medicines education practices in the home and (3) the interaction in medicines education between the home and at school.

Design:

Mixed-methods case study.

Setting:

Pupils and their parents in one comprehensive school in Finland.

Method:

Before an educational intervention with Year 4 (aged 10–11 years) and Year 7 (aged 13–14 years) students, parents completed a background survey concerning their perceptions, beliefs and knowledge of medicines ( n = 250). Following the intervention, interviews with 12 mothers and 12 children, and medicine cabinet studies ( n = 10) were conducted. Quantitative data were analysed using K-mean cluster analysis to see whether respondents could be divided into different clusters based on their attitudes towards medicines. Qualitative data were analysed using theory-guided content analysis to obtain a picture of home medicines education.

Results:

Participants, mostly mothers, were divided into different types of medicine educators, whose attitudes towards medicines were either positive or neutral. Medicine consumption practices varied between families, but medicines were usually discussed when the child, a family member, a relative or a friend had a long-term illness; when a family member was suffering from a sickness; and while taking a medicine. In general, interaction between the home and the school was rather limited.

Conclusion:

The majority of mothers exhibited a strong reliance on public systems of health care. Greater interaction between schools and the home is needed in Finnish medicines education.
Feeding Tubes and Health Care Service Utilization in Amyotrophic Lateral Sclerosis: Benefits and Limits to a Retrospective, Multicenter Study Using Big Data
Authors: Swetz Keith M. , Peterson Stephanie M. , Sangaralingham Lindsey R. , Hurt Ryan T. , Dunlay Shannon M. , Shah Nilay D. , Tilburt Jon C.
Published: September 2017

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurologic disorder with predictable challenges regarding disease progression and end-of-life care. These include need for respiratory and nutritional support. Little is known about how such choices impact end-of-life health service utilization for these patients. Using OptumLabs Data Warehouse, a large administrative claims database with more than 150 million privately insured, geographically diverse enrollees, we sought to explore outcomes associated with the use of enteral nutrition (EN). Patients were of age ≥18 years, with first ALS diagnosis during calendar years 2006-2012, and 6 months of continuous health plan coverage before first diagnosis. EN use was identified using procedure codes. Data were summarized descriptively. Among 1974 patients with ALS, mean age was 60.0 ± 12.5 years, 41.8% were women, and 9.7% demonstrated use of EN. Median time from ALS diagnosis to evidence of EN was 211 days (interquartile range [IQR]: 70-426). Those receiving EN had greater aggregate comorbidity (47% with Charlson-Deyo Comorbidity Index ≥ 3 vs only 27% in non-EN subset). In total, 38.1% of patients had at least 1 hospitalization, with median time to hospitalization of 162 days. Unfortunately, the EN group ended coverage a median of 155 days after EN started (IQR: 63.5-388), thereby limiting ability to capture outcomes. Although many ALS patients were identified, EN use was lower than expected, due to being earlier in disease trajectory and lost to follow-up with transition from private insurance. As such, databases exclusively including privately insured patients may be suboptimal for detecting late complications of protracted illnesses.
Experience Value or Satiety? The Effects of the Amount and Variety of Tourists’ Activities on Perceived Experience
Authors: Antón Carmen , Camarero Carmen , Laguna-García Marta
Published: September 2017

Recently, tourist companies and destinations have moved from designing products to focusing on creating experiences that engage and involve the tourist. Although the intensity (intensiveness) and variety of the experience (extensiveness) leads tourists to feel their experience has been livelier and richer and to appraise it positively, it might also bring unwanted consequences such as a feeling of saturation. The present study seeks to explore the role played by the value of perceived experience and of satiety as mediators between experience intensity and variety as well as future visitor behavior. The empirical study reveals that the variety of activities improves the perceived experience value, whereas investing too much time reduces the value and causes satiety in the tourist. Moreover, while the experience value reinforces the intention to return, the intention to recommend and the intensification of the experience, the feeling of satiety reduces the intention to return and recommend.
Talent development in Chinese and Swiss music students
Authors: Petersen Suse
Published: September 2017

Musical talent development and the factors that influence it—such as family or peers—have been widely researched, especially in a Western setting. Despite the growing body of research in non-Western cultures and regions, there is still a lack of research comparing the factors and perceptions of musical talent development between Western and Asian settings. This interview study compared Swiss and Chinese music students’ ( N = 19) musical talent development and the factors influencing musical talent during childhood and adolescence, their professional aims, and their perception of internal and external factors affecting talent development. The students had similar opinions regarding the role of their teachers, the roles of internal and external factors in talent development, and their career goals. However, the students from China and Switzerland differed in their experiences of making and discussing music with peers, in the difficulties experienced during their music education, and in their relationship with their families. The results are a starting point for further comparative research on the perception and development of musical talent, and offer material for a mutual understanding of music students’ backgrounds in countries with differing music education traditions.
Constructing accounts of organisational failure: Policy, power and concealment
Authors: Sheaff Mike
Published: September 2017

An example of contracting arrangements within the National Health Service (NHS) provides the focus for considering accounts of organisational behaviour and failure. Public accounts of the outcome are contrasted with information disclosed in response to Freedom of Information Act (FOIA) requests. While the former focused on shortcomings in commercial expertise, sometimes at lower levels within organisational hierarchies, the latter suggests a need to consider the environment of social networks and power relationships. The data suggests obstacles to information flows across organisational boundaries were a contributory cause of failure, but a desire to present the implementation of policy in a positive light encouraged subsequent concealment of what Goffman (1959/1990) described as ‘dark secrets’. Through this example, the article provides an exploratory use of FOIA to examine social processes that frequently elude investigation.
Robust optimal planning and control of non-periodic bipedal locomotion with a centroidal momentum model
Authors: Zhao Ye , Fernandez Benito R , Sentis Luis
Published: September 2017

This study presents a theoretical method for planning and controlling agile bipedal locomotion based on robustly tracking a set of non-periodic keyframe states. Based on centroidal momentum dynamics, we formulate a hybrid phase-space planning and control method that includes the following key components: (i) a step transition solver that enables dynamically tracking non-periodic keyframe states over various types of terrain; (ii) a robust hybrid automaton to effectively formulate planning and control algorithms; (iii) a steering direction model to control the robot’s heading; (iv) a phase-space metric to measure distance to the planned locomotion manifolds; and (v) a hybrid control method based on the previous distance metric to produce robust dynamic locomotion under external disturbances. Compared with other locomotion methodologies, we have a large focus on non-periodic gait generation and robustness metrics to deal with disturbances. This focus enables the proposed control method to track non-periodic keyframe states robustly over various challenging terrains and under external disturbances, as illustrated through several simulations.
Validation of a Revised Observation-Based Assessment Tool for Children Birth Through Kindergarten: The COR Advantage
Authors: Wakabayashi Tomoko , Claxton Jill , Smith Everett V.
Published: September 2017

The Child Observation Record (COR), initially developed in 1993 by HighScope Educational Research Foundation, is an observation-based instrument that provides systematic assessment of young children’s knowledge and abilities in all major areas of development. Teachers or caregivers spend a few minutes each day writing brief notes or “anecdotes” that objectively describe significant episodes of young children’s activities. The anecdotes are then classified and scored according to various COR categories, items, and levels, providing a comprehensive portrait of each child’s developmental gains and the progress of the group as a whole. In 2012, the COR was revised to span the developmental range from infancy and toddlerhood through kindergarten. The validation evidence for the revised instrument, the COR Advantage, was gathered in two phases—an initial validation phase and the multi-state implementation validation phase. The results from both phases show that the COR Advantage generates scores which are internally consistent and inferences made from scores that are valid for (a) documenting the developmental trajectories of children from birth through kindergarten in all key areas of children’s development, and (b) capturing developmental milestones of children from varied backgrounds with diverse abilities when used by early childhood professionals.
Bringing Propaganda Back into News Media Studies
Authors: Zollmann Florian
Published: September 2017

With the ascendance of liberal democracy, propaganda activities have vastly increased. The main aim of propaganda has been to protect state-corporate power from the threat of public understanding and participation. Because of its societal importance for public opinion formation, the news media constitutes an obvious channel for the dissemination of propaganda. However, contemporary communication, media and journalism studies have mostly neglected to critically assess the news media’s role in producing and distributing propaganda. In fact, despite of the news media’s integration into the state-corporate nexus, the term propaganda is rarely used in academic treatises on the news media. Furthermore, only a small number of scholars have engaged in elaborating a systematic understanding of the manifold propaganda techniques that are currently applied in liberal democracies. To fill these research gaps, this article maps out various concepts of propaganda and relates them to the process and content of the news media. On the basis of theoretical and empirical studies, the article demonstrates how different forms of propaganda can manifest in news media content. Based on an integration with, as well as a development of, existing literature, the essay aims to build a tool box that can be applied and refined in future studies in order to detect propaganda in news media texts.
Switching decentralized control of a platoon of vehicles with time-varying heterogeneous delay: A safe and dense spacing policy
Authors: Chehardoli Hossein , Homaeinezhad Mohammad R.
Published: September 2017

In this paper the problem of decentralized switching control of a platoon of vehicles in the presence of heterogeneous time-varying communication and parasitic delays is investigated. A neighbor-based linear decentralized controller using the relative measurements is considered for each vehicle. The communication structure of the platoon is assumed to be time-varying. Therefore, the closed-loop dynamics of the platoon is in the form of switched linear multiple-delay systems. Compared to previous research, the communication structure of the platoon is assumed to be general. A safe and dense spacing policy is used to adjust inter-vehicle distances. The internal stability analysis of the platoon is done by employing Lyapunov–Razumikhin and Lyapunov–Krasovskii theorems. Afterwards, some conditions on control parameters assuring string stability are obtained by introducing a new theorem. Simulation studies are carried out to show the effectiveness of the proposed methods.
Magnetorheological damper–based positioning system with power generation
Authors: Sapiński Bogdan , Węgrzynowski Marcin , Nabielec Jerzy
Published: September 2017

This study investigates a newly developed positioning system based on a rotary magnetorheological damper with power generation capability, comprising an electromagnetic power generator (energy extractor) generating electrical power, an magnetorheological damper which alters the damping characteristics of the system and an electrical interface, connected in between the coil of the generator and the damper control coil, which conditions the voltage output from the generator. Structural configurations of the damper and the generator are outlined, and the results of their testing and the testing done on the entire system are summarised, covering the tests conducted with and without the interface, under the idle run and under load in the assumed velocity range. The objective of the work is to examine the performance of the proposed positioning system through experiments. Results of the system testing in the uncontrolled case (passive system) and in the controlled one (semi-active system) in a purpose-built test rig are compared and discussed. Three design options of the electrical system controlling the damper are explored. In the first option, the damper is assumed to be controlled starting from the initial moment of the motor shaft’s motion, and in the second option, the control action begins at the instant when the motor shaft assumes the present position. The third variant is similar to the first one except that an additional condenser is connected behind the Graetz bridge. The results confirm the adequacy of the developed positioning system and demonstrate an improvement in control of the system’s dynamic behaviour.