bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized-Controlled Trial Pilot Study Examining the Effect of Pelvic Floor Muscle Training on the Irisin Concentration in Overweight or Obese Elderly Women with Stress Urinary Incontinence
Authors: Weber-Rajek Magdalena , Radzimińska Agnieszka , Strączyńska Agnieszka , Strojek Katarzyna , Piekorz Zuzanna , Kozakiewicz Mariusz , Styczyńska Hanna
Published: August 2019

Objective. This study aimed to examine the effect of pelvic floor muscle training on the irisin (Ir) concentration in overweight or obese elderly women with stress urinary incontinence. Methods. The number of participants included in analysis was 49: 28 women in the experimental group and 21 women in the control group. The experimental group (EG) underwent pelvic floor muscle training, whereas no therapeutic intervention was applied to the control group (CG). Irisin concentration, severity of urinary incontinence (RUIS), and body mass index (BMI) were measured in all women at the initial and final assessments. Results. By comparing the initial and final assessment results we have been able to demonstrate statistically significant differences in the measured variables in the experimental group. No statistically significant differences in the measured variables were reported for the control group at the initial and final assessments. Moderate negative correlation was observed between the BMI results with the irisin concentration results in the EG at the initial assessment and no correlation at the final assessment. Weak positive correlation was observed between the BMI results with the irisin concentration in the CG at the initial and final assessment. Conclusion. Further studies are necessary to observe the regulation of irisin concentration and explain mechanisms underlying these effects.
Preconditioning of Rat Bone Marrow-Derived Mesenchymal Stromal Cells with Toll-Like Receptor Agonists
Authors: Evaristo-Mendonça Fabiana , Sardella-Silva Gabriela , Kasai-Brunswick Tais Hanae , Campos Raquel Maria Pereira , Domizi Pablo , Santiago Marcelo Felippe , de Melo Reis Ricardo Augusto , Mendez-Otero Rosalia , Ribeiro-Resende Victor Túlio , Pimentel-Coelho Pedro Moreno
Published: August 2019

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are dynamic cells that can sense the environment, adapting their regulatory functions to different conditions. Accordingly, the therapeutic potential of BM-MSCs can be modulated by preconditioning strategies aimed at modifying their paracrine action. Although rat BM-MSCs (rBM-MSCs) have been widely tested in preclinical research, most preconditioning studies have employed human and mouse BM-MSCs. Herein, we investigated whether rBM-MSCs modify their phenotype and paracrine functions in response to Toll-like receptor (TLR) agonists. The data showed that rBM-MSCs expressed TLR3, TLR4, and MDA5 mRNA and were able to internalize polyinosinic-polycytidylic acid (Poly(I:C)), a TLR3/MDA5 agonist. rBM-MSCs were then stimulated with Poly(I:C) or with lipopolysaccharide (LPS, a TLR4 agonist) for 1 h and were grown under normal culture conditions. LPS or Poly(I:C) stimulation did not affect the viability or the morphology of rBM-MSCs and did not modify the expression pattern of key cell surface markers. Poly(I:C) did not induce statistically significant changes in the release of several inflammatory mediators and VEGF by rBM-MSCs, although it tended to increase IL-6 and MCP-1 secretion, whereas LPS increased the release of IL-6, MCP-1, and VEGF, three factors that were constitutively secreted by unstimulated cells. The neurotrophic activity of the conditioned medium from unstimulated and LPS-preconditioned rBM-MSCs was investigated using dorsal root ganglion explants, showing that soluble factors produced by unstimulated and LPS-preconditioned rBM-MSCs can stimulate neurite outgrowth similarly, in a VEGF-dependent manner. LPS-preconditioned cells, however, were slightly more efficient in increasing the number of regrowing axons in a model of sciatic nerve transection in rats. In conclusion, LPS preconditioning boosted the production of constitutively secreted factors by rBM-MSCs, without changing their mesenchymal identity, an effect that requires further investigation in exploratory preclinical studies.
Diagnostic and Clinical Significance of Serum Levels of D-Lactate and Diamine Oxidase in Patients with Crohn’s Disease
Authors: Cai Jierui , Chen Hong , Weng Meiling , Jiang Shuyu , Gao Jie
Published: August 2019

Background. Crohn’s disease (CD) is a chronic intestinal inflammatory disease. An ideal laboratory marker that can predict the prognosis in terms of relapse of the disease is clinically desirable. Methods. A total of 59 CD patients were enrolled in this study. Enzyme-Linked Immunosorbent Assay (ELISA) was used to quantitatively detect the content of D-lactate (D-LA) and the diamine oxidase (DAO) levels in sera obtained from patients and 28 healthy controls. The correlation between these two biomarkers and disease activity scores was assessed. In addition, the ROC curve was used to evaluate the diagnostic accuracy of these two biomarkers. Results. The levels of D-LA in the serum of CD patients in the active stage and remission stage were 16.08±4.8 mg/L and 11.16±3.17 mg/L, respectively, and the difference was statistically significant (t=4.67, P<0.001). DAO levels were significantly higher in patients with the active stage compared to controls. The levels of D-LA and DAO in CD patients were positively correlated with the disease activity (r=0.68 and 0.53, respectively, P<0.05). The area under the ROC curve (AUC) when CD activity was diagnosed with D-LA and DAO alone was 0.815 and 0.748, respectively. The diagnostic efficacy of the two biomarkers was not significantly different from that of the erythrocyte sedimentation (ESR) and hypersensitive C-reactive protein (CRP) (P>0.05). However, the area under the curve was 0.861 (0.746, 0.937) when the diagnosis was performed using a combination of D-LA, DAO, CRP, and ESR, which was significantly higher than when CRP or ESR were tested alone (P<0.05). Conclusions. D-LA and DAO have a good prognostic value for CD activity. Rational combined use of biomarkers can significantly improve the diagnostic efficiency.
Tracking Control Design in Nonlinear Multivariable Systems: Robotic Applications
Authors: Scaglia Gustavo , Serrano Emanuel , Rosales Andres , Albertos Pedro
Published: August 2019

In this work, a controller design technique called linear algebra based controller (LABC) is presented. The controller is obtained following a systematic procedure that is summarized in this work. In addition, the influence of additive uncertainty on the tracking error is analyzed, and a solution using integrators is proposed. A mobile robot is used as a benchmark to test the performance of the proposed algorithms. In addition, implementation to other systems such as marine vessel is referenced. In this work, the design of controllers in continuous and discrete time is included and experimental and simulation results are shown in a Pioneer 3AT mobile robot. Comparisons are also shown with other controllers proposed in the literature.
A Low Ankle-Brachial Index and High Brachial-Ankle Pulse Wave Velocity Are Associated with Poor Cognitive Function in Patients Undergoing Hemodialysis
Authors: Wu Ping-Hsun , Lin Yi-Ting , Wu Pei-Yu , Huang Jiun-Chi , Chen Szu-Chia , Chang Jer-Ming , Chen Hung-Chun
Published: August 2019

Patients with end-stage renal disease (ESRD) have an increased risk of both impaired cognitive function and peripheral artery disease (PAD) than the general population. The association between PAD and dementia is recognized, but there are limited studies in patients with ESRD. The aim of this study was to evaluate the relationship between ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) and cognitive impairment in patients receiving hemodialysis (HD). We enrolled 136 prevalent HD patients (mean age 59.3±10.5 years, 55.9% male). Cognitive performance was measured using the Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI) by trained psychiatrists. Associations between the cognitive function and ABI and baPWV were assessed using multiple linear regression analysis. Compared with HD patients with ABI≥0.9, patients with ABI<0.9 had lower MoCA score (p=0.027) and lower CASI score but did not achieve significant level (p=0.056). In the multivariate stepwise linear regression analysis, ABI (per 0.1) was independently positively associated with the MoCA score (β coefficient=0.62, p=0.011) and the CASI score (β coefficient=1.43, p=0.026). There is a negative association between baPWV (per 100 cm/s) and CASI (β coefficient=−0.70, p=0.009). In conclusion, a low ABI or high baPWV was associated with a lower cognitive function in HD patients.
Oxidized Cell-Free DNA Is a Factor of Stress Signaling in Radiation-Induced Bystander Effects in Different Types of Human Cells
Authors: Konkova Marina S. , Kaliyanov Andrew A. , Sergeeva Vasilina A. , Abramova Margarita S. , Kostyuk Svetlana V.
Published: August 2019

In pathology or under damaging conditions, the properties of cell-free DNA (cfDNA) change. An example of such change is GC enrichment, which drastically alters the biological properties of cfDNA. GC-rich cfDNA is a factor of stress signaling, whereas genomic cfDNA is biologically inactive. GC-rich cfDNA stimulates TLR9-MyD88-NF-κB signaling cascade, leading to an increase in proinflammatory cytokine levels in the organism. In addition, GC-rich DNA is prone to oxidation and oxidized cfDNA can stimulate secondary oxidative stress. This article is a review of works dedicated to the investigation of a low-dose ionizing radiation effect, a bystander effect, and the role of cfDNA in both of these processes.
Establishing the Impact of Vascular Damage on Tumor Response to High-Dose Radiation Therapy
Authors: Castle Katherine D. , Kirsch David G.
Published: August 2019

Approximately half of all patients with cancer receive radiotherapy, which is conventionally delivered in relatively small doses (1.8–2 Gy) per daily fraction over one to two months. Stereotactic body radiation therapy (SBRT), in which a high daily radiation dose is delivered in 1 to 5 fractions, has improved local control rates for several cancers. However, despite the widespread adoption of SBRT in the clinic, controversy surrounds the mechanism by which SBRT enhances local control. Some studies suggest that high doses of radiation (≥10 Gy) trigger tumor endothelial cell death, resulting in indirect killing of tumor cells through nutrient depletion. On the other hand, mathematical models predict that the high radiation dose per fraction used in SBRT increases direct tumor cell killing, suggesting that disruption of the tumor vasculature is not a critical mediator of tumor cure. Here, we review the application of genetically engineered mouse models to radiosensitize tumor cells or endothelial cells to dissect the role of these cellular targets in mediating the response of primary tumors to high-dose radiotherapy in vivo. These studies demonstrate a role for endothelial cell death in mediating tumor growth delay, but not local control following SBRT.
First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma
Authors: Allen Bryan G. , Bodeker Kellie L. , Smith Mark C. , Monga Varun , Sandhu Sonia , Hohl Raymond , Carlisle Thomas , Brown Heather , Hollenbeck Nancy , Vollstedt Sandy , Greenlee Jeremy D. , Howard Matthew A. , Mapuskar Kranti A. , Seyedin Steven N. , Caster Joseph M. , Jones Karra A. , Cullen Joseph J. , Berg Daniel , Wagner Brett A. , Buettner Garry R. , TenNapel Mindi J. , Smith Brian J. , Spitz Douglas R. , Buatti John M.
Published: August 2019

Purpose:

Standard treatment for glioblastoma (GBM) includes surgery, radiation therapy (RT), and temozolomide (TMZ), yielding a median overall survival (OS) of approximately 14 months. Preclinical models suggest that pharmacologic ascorbate (P-AscH−) enhances RT/TMZ antitumor effect in GBM. We evaluated the safety of adding P-AscH− to standard RT/TMZ therapy.

Patients and Methods:

This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH−) and an adjuvant (ADJ) phase (post RT/TMZ/P-AscH− phase). Eight P-AscH− dose cohorts were evaluated in the RT phase until targeted plasma ascorbate levels were achieved (≥20 mmol/L). In the ADJ phase, P-AscH− doses were escalated in each subject at each cycle until plasma concentrations were ≥20 mmol/L. P-AscH− was infused 3 times weekly during the RT phase and 2 times weekly during the ADJ phase continuing for six cycles or until disease progression. Adverse events were quantified by CTCAE (v4.03).

Results:

Eleven subjects were evaluable. No dose-limiting toxicities occurred. Observed toxicities were consistent with historical controls. Adverse events related to study drug were dry mouth and chills. Targeted ascorbate plasma levels of 20 mmol/L were achieved in the 87.5 g cohort; diminishing returns were realized in higher dose cohorts. Median progression-free survival (PFS) was 9.4 months and median OS was 18 months. In subjects with undetectable MGMT promoter methylation (n = 8), median PFS was 10 months and median OS was 23 months.

Conclusions:

P-AscH−/RT/TMZ is safe with promising clinical outcomes warranting further investigation.
Late Gadolinium Enhancement Magnetic Resonance Imaging Guided Treatment of Post–Atrial Fibrillation Ablation Recurrent Arrhythmia
Authors: Fochler Franziska , Yamaguchi Takanori , Kheirkahan Mobin , Kholmovski Eugene G. , Morris Alan K. , Marrouche Nassir F.
Published: August 2019

Background:

Macroreentrant atrial tachycardia (AT) accounts for 40% to 60% of recurrent atrial arrhythmias after atrial fibrillation (AF) ablation. To describe late gadolinium enhancement magnetic resonance imaging (LGE-MRI)–detected scar-based dechanneling as new ablation strategy to treat ATs after AF ablation.

Methods:

Data from 102 patients who underwent initial AF ablation and repeat ablation for recurrent atrial arrhythmia within 1-year follow-up were analyzed. All patients underwent LGE-MRI before initial and repeat ablation. Depending on the recurrent rhythm, patients with AF and AT recurrence were assigned to group 1 or 2, respectively. Group 1 underwent fibrosis homogenization as second procedure. Group 2 underwent LGE-MRI–detected scar-based dechanneling. Both groups underwent reisolation of pulmonary veins if necessary.

Results:

Forty-six patients (45%) presented with AF, and 56 patients (55%) presented with AT recurrence during follow-up after initial ablation. In the first 25 patients from group 2, the AT was electroanatomically mapped, and a critical isthmus was defined. It was found that those isthmi were located in the regions with nontransmural scarring detected by LGE-MRI. In the last 31 patients from group 2, an empirical LGE-MRI–based dechanneling was performed solely based on the LGE-MRI results. During 1-year follow-up after second ablation, 67% patients in group 1 and 64% patients in group 2 were free from recurrence (log-rank,
P
=1.000). In group 2, 64% in the electroanatomically guided and 65% in the LGE-MRI dechanneling group were free from recurrence (log-rank,
P
=0.900).

Conclusions:

Anatomic targeting of LGE-MRI–detected gaps and superficial atrial scar is feasible and effective to treat recurrent arrhythmias post-AF ablation. Homogenization of existing scar is the appropriate treatment for recurrent AF, whereas dechanneling of existing isthmi seems the right approach for patients recurring with AT.
Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease
Authors: Agha Golareh , Mendelson Michael M. , Ward-Caviness Cavin K. , Joehanes Roby , Huan TianXiao , Gondalia Rahul , Salfati Elias , Brody Jennifer A. , Fiorito Giovanni , Bressler Jan , Chen Brian H. , Ligthart Symen , Guarrera Simonetta , Colicino Elena , Just Allan C. , Wahl Simone , Gieger Christian , Vandiver Amy R. , Tanaka Toshiko , Hernandez Dena G. , Pilling Luke C. , Singleton Andrew B. , Sacerdote Carlotta , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Li Yun , Zhang Guosheng , Stewart James D. , Floyd James S. , Wiggins Kerri L. , Rotter Jerome I. , Multhaup Michael , Bakulski Kelly , Horvath Steven , Tsao Philip S. , Absher Devin M. , Vokonas Pantel , Hirschhorn Joel , Fallin M. Daniele , Liu Chunyu , Bandinelli Stefania , Boerwinkle Eric , Dehghan Abbas , Schwartz Joel D. , Psaty Bruce M. , Feinberg Andrew P. , Hou Lifang , Ferrucci Luigi , Sotoodehnia Nona , Matullo Giuseppe , Peters Annette , Fornage Myriam , Assimes Themistocles L. , Whitsel Eric A. , Levy Daniel , Baccarelli Andrea A.
Published: August 2019

Background:

DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

Methods:

Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

Results:

Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.

Conclusion:

Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.
Diastolic Blood Pressure J-Curve Phenomenon in a Tertiary-Care Hypertension Clinic
Authors: Lip Stefanie , Tan Li En , Jeemon Panniyammakal , McCallum Linsay , Dominiczak Anna F. , Padmanabhan Sandosh
Published: August 2019

Concerns exist regarding the potential increased cardiovascular risk from lowering diastolic blood pressure (DBP) in hypertensive patients. We analyzed 30-year follow-up data of 10 355 hypertensive patients attending the Glasgow Blood Pressure Clinic. The association between blood pressure during the first 5 years of treatment and cause-specific hospital admissions or mortality was analyzed using multivariable adjusted Cox proportional hazard models. The primary outcome was a composite of cardiovascular admissions and deaths. DBP showed a U-shaped association (nadir, 92 mm Hg) for the primary cardiovascular outcome hazard and a reverse J-shaped association with all-cause mortality (nadir, 86 mm Hg) and noncardiovascular mortality (nadir, 92 mm Hg). The hazard ratio for the primary cardiovascular outcome after adjustment for systolic blood pressure was 1.38 (95% CI, 1.18–1.62) for DBP <80 compared with DBP of 80 to 89.9 mm Hg (referrant), and the subdistribution hazard ratio after accounting for competing risk was 1.33 (1.17–1.51) compared with DBP ≥80 mm Hg. Cause-specific nonfatal outcome analyses showed a reverse J-shaped relationship for myocardial infarction, ischemic heart disease, and heart failure admissions but a U-shaped relationship for stroke admissions. Age-stratified analyses showed DBP had no independent effect on stroke admissions among the older patient subgroup (≥60 years of age), but the younger subgroup showed a clear U-shaped relationship. Intensive blood pressure reduction may lead to unintended consequences of higher healthcare utilization because of increased cardiovascular morbidity, and this merits future prospective studies. Low on-treatment DBP is associated with increased risk of noncardiovascular mortality, the reasons for which are unclear.
High-Protein Diet–Induced Glomerular Hyperfiltration Is Dependent on Neuronal Nitric Oxide Synthase β in the Macula Densa via Tubuloglomerular Feedback Response
Authors: Wei Jin , Zhang Jie , Jiang Shan , Wang Lei , Persson A. Erik G. , Liu Ruisheng
Published: August 2019

It is well known that high protein intake increases glomerular filtration rate. Evidence from several studies indicated that NO and tubuloglomerular feedback (TGF) mediate the effect. However, a recent study with a neuronal NO synthase-α knockout model refuted this mechanism and concluded that neither neuronal NO synthase nor TGF response is involved in the protein-induced hyperfiltration. To examine the discrepancy, this study tested a hypothesis that neuronal NO synthase-β in the macula densa mediates the high-protein diet–induced glomerular hyperfiltration via TGF mechanism. We examined the effects of high protein intake on NO generation at the macula densa, TGF response, and glomerular filtration rate in wild-type and macula densa–specific neuronal NO synthase KO mice. In wild-type mice, high-protein diet increased kidney weight, glomerular filtration rate, and renal blood flow, while reduced renal vascular resistance. TGF response in vivo and in vitro was blunted, and NO generation in the macula densa was increased following high-protein diet, associated with upregulations of neuronal NO synthase-β expression and phosphorylation at Ser1417. In contrast, these high-protein diet–induced changes in NO generation at the macula densa, TGF response, renal blood flow, and glomerular filtration rate in wild-type mice were largely attenuated in macula densa–specific neuronal NO synthase KO mice. In conclusion, we demonstrated that high-protein diet–induced glomerular hyperfiltration is dependent on neuronal NO synthase β in the macula densa via TGF response.
Association Between Systolic and Diastolic Blood Pressure Variability and the Risk of End-Stage Renal Disease
Authors: Bae Eun Hui , Lim Sang Yup , Han Kyung-Do , Oh Tae Ryom , Choi Hong Sang , Kim Chang Seong , Ma Seong Kwon , Kim Soo Wan
Published: August 2019

Recent data suggest that visit-to-visit variability of blood pressure (BP) is associated with cardiovascular events. We evaluated the role of BP variability as a determinant of end-stage renal disease (ESRD). Using nationally representative data from the Korean National Health Insurance System, 8 199 089 subjects had been enrolled during 2009 to 2010 who were free of ESRD and underwent ≥3 health examinations during 2005 to 2010 were followed to the end of 2017. BP variability was measured using the coefficient of variation, SD, and variability independent of the mean. The primary outcome was the development of ESRD, defined as a combination of the relevant disease code and the initiation of renal replacement therapy. The χ
2
test,
t
test, and log-rank test were used in the statistical analysis. There were 16 567 cases of ESRD during a median follow-up of 7.89±0.88 years. The highest quartile of systolic or diastolic BP showed a higher incident rate of ESRD compared with the other 3 quartiles. It was augmented in patients with the highest quartile of both systolic and diastolic BP variabilities. Among patients with the highest quartile of systolic and diastolic BP variabilities, the uncontrolled hypertension group (>140/90 mm Hg) taking antihypertensive medication showed the highest incidence rate of ESRD. These results were consistent when modeling variability of BP using coefficient of variation, SD, and variability independent of the mean and in various sensitivity analyses. Systolic and diastolic BP variabilities were independently associated with an increased incidence of ESRD, and it was augmented when both variabilities were present together.
Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin‐6–Mediated Changes in Connexin Expression
Authors: Lazzerini Pietro Enea , Laghi‐Pasini Franco , Acampa Maurizio , Srivastava Ujala , Bertolozzi Iacopo , Giabbani Beatrice , Finizola Francesco , Vanni Francesca , Dokollari Aleksander , Natale Mariarita , Cevenini Gabriele , Selvi Enrico , Migliacci Nicola , Maccherini Massimo , Boutjdir Mohamed , Capecchi Pier Leopoldo
Published: August 2019

Background

Systemic inflammation is a strong predictor of atrial fibrillation. A key role for electrical remodeling is increasingly recognized, and experimental data suggest that inflammatory cytokines can directly affect connexins resulting in gap‐junction dysfunction. We hypothesized that systemic inflammation, regardless of its origin, promotes atrial electric remodeling in vivo, as a result of cytokine‐mediated changes in connexin expression.

Methods and Results

Fifty‐four patients with different inflammatory diseases and elevated C‐reactive protein were prospectively enrolled, and electrocardiographic P‐wave dispersion indices, cytokine levels (interleukin‐6, tumor necrosis factor‐α, interleukin‐1, interleukin‐10), and connexin expression (connexin 40, connexin 43) were measured during active disease and after reducing C‐reactive protein by >75%. Moreover, peripheral blood mononuclear cells and atrial tissue specimens from an additional sample of 12 patients undergoing cardiac surgery were evaluated for atrial and circulating mRNA levels of connexins. Finally, in vitro effects of interleukin‐6 on connexin expression were studied in HL‐1 mouse atrial myocytes. In patients with active inflammatory diseases, P‐wave dispersion indices were increased but rapidly decreased within days when C‐reactive protein normalizes and interleukin‐6 levels decline. In inflammatory disease patients, both P‐wave dispersion indices and interleukin‐6 changes were inversely associated with circulating connexin levels, and a positive correlation between connexin expression in peripheral blood mononuclear cells and atrial tissue was demonstrated. Moreover, interleukin‐6 significantly reduced connexin expression in HL‐1 cells.

Conclusions

Our data suggest that regardless of specific etiology and organ localization, systemic inflammation, via interleukin‐6 elevation, rapidly induces atrial electrical remodeling by down‐regulating cardiac connexins. Although transient, these changes may significantly increase the risk for atrial fibrillation and related complications during active inflammatory processes.
Effect of Baseline Kidney Function on the Risk of Recurrent Stroke and on Effects of Intensive Blood Pressure Control in Patients With Previous Lacunar Stroke: A Post Hoc Analysis of the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes)
Authors: Agarwal Adhish , Cheung Alfred K. , Ma Jianing , Cho Monique , Li Man
Published: August 2019

Background

We conducted a post hoc analysis of the SPS3 (Secondary Prevention of Small Subcortical Strokes) Trial to examine the association of chronic kidney disease (
CKD
) with
recurrent
stroke, and to assess whether baseline renal function modifies the effects of intensive systolic blood pressure control in patients with previous stroke.

Methods and Results

A total of 3020 patients with recent magnetic resonance imaging–defined symptomatic lacunar infarctions were randomized to a systolic blood pressure target of <130 mm Hg versus 130 to 149 mm Hg. Predefined primary outcomes were (all‐recurrent) stroke and a composite of stroke, acute myocardial infarction, or all‐cause death; secondary outcomes were acute myocardial infarction, all‐cause death, and intracerebral hemorrhage individually. Among 3017 patients with baseline estimated glomerular filtration rate measurements, we evaluated, using Cox proportional hazards models, the association of
CKD
with recurrent stroke and effects of the blood pressure targets on outcomes using baseline estimated glomerular filtration rate both as a categorical and linear variable. Regardless of the randomized treatment,
CKD
at baseline was significantly associated with an increased risk of the primary cardiovascular composite outcome (hazard ratio, 1.7; 95% CI, 1.4–2.1), and all‐recurrent stroke (1.5; 1.1–2.0). However, the effects of the lower systolic blood pressure intervention on the primary outcome were not influenced by baseline
CKD
status (
P
for interaction=0.62).

Conclusions

CKD
increases the risk of recurrent stroke by 50% in patients with previous lacunar stroke. We found no definitive evidence that renal dysfunction modifies the effects of systolic blood pressure control in patients with previous stroke. Conclusive evidence for this will require adequately powered studies with moderate‐to‐advanced
CKD
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00059306.
Systematic Review of Malpractice Litigation in the Diagnosis and Treatment of Acute Stroke
Authors: Haslett Jack J. , Genadry Lisa , Zhang Xiangnan , LaBelle Lindsey A. , Bederson Joshua , Mocco J , Kellner Christopher P.
Published: August 2019

Background and Purpose—

The emergency management of stroke is complex and highly time-sensitive. Recent landmark trials demonstrating the strong benefit of thrombectomy have led to rapid change in stroke management. This article reviews a large number of medical malpractice lawsuits related to the emergency management of stroke to characterize factors involved in these lawsuits.

Methods—

Three large legal databases were used to search for jury verdicts and settlements in cases related to the acute care of stroke patients in the United States. Search terms included “stroke” and “medical malpractice.” Cases were screened to include only cases in which the allegation involved negligence in the acute care of a patient suffering a stroke.

Results—

We found 246 medical malpractice cases related to the acute management of ischemic stroke and 26 related to intracranial hemorrhage. Seventy-one cases specifically alleged a failure to treat with tPA (tissue-type plasminogen activator) and 7 cases alleged a failure to treat, or to timely treat, with thrombectomy. Overall there were 151 cases (56%) which ended with no payout, 74 cases (27%) were settled out of court, and 47 cases (17%) went to court and resulted in a verdict for the plaintiff. The average payout in settlements was $1 802 693, and the average payout in plaintiff verdicts was $9 705 099.

Conclusions—

Malpractice litigation is a risk in acute stroke care and can lead to significant financial consequences. The majority of malpractice lawsuits related to the emergency management of stroke allege a failure to diagnose and failure to treat. Allegations of a failure to treat acute ischemic stroke with tPA were frequently found and are common in lawsuits. Allegations of a failure to treat a large vessel occlusion with thrombectomy were less frequently found. Given recent changes in practice guidelines and the demonstrated strong treatment effect of thrombectomy, it is likely that such litigation will increase in the coming years.
Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Asians With Atrial Fibrillation
Authors: Xue Zhengbiao , Zhang Hao
Published: August 2019

Background and Purpose—

Several randomized trials and real-world studies have reported the efficacy and safety of non–vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with atrial fibrillation; and therefore, this meta-analysis was aimed to compare the effects of NOACs with warfarin for atrial fibrillation stroke prevention in Asians.

Methods—

The PubMed and Embase databases were searched from January 2009 to February 2019 for studies on comparisons of NOACs versus warfarin in Asians. Risk ratios (RRs) with 95% CIs were pooled using a random-effects model.

Results—

Five NOAC trials and 21 observational cohorts were included. For the NOAC trials, compared with warfarin, NOACs was associated with reduced risks of stroke or systemic embolism (RR, 0.73; 95% CI, 0.59–0.90), all-cause death (RR, 0.83; 95% CI, 0.73–0.95), major bleeding (RR, 0.59; 95% CI, 0.48–0.72), and intracranial bleeding (RR, 0.36; 95% CI, 0.26–0.49). For the real-world data, compared with warfarin, NOACs was associated with decreased rates of stroke or systemic embolism (RR, 0.75; 95% CI, 0.68–0.82), ischemic stroke (RR, 0.70; 95% CI, 0.59–0.83), myocardial infarction (RR, 0.74; 95% CI, 0.58–0.93), all-cause death (RR, 0.67; 95% CI, 0.59–0.77), major bleeding (RR, 0.63; 95% CI, 0.55–0.73), intracranial bleeding (RR, 0.50; 95% CI, 0.43–0.59), and gastrointestinal bleeding (RR, 0.65; 95% CI, 0.51–0.84). The results did not change in the subgroup analyses based on the type and dose of NOACs.

Conclusions—

Based on published NOAC trials and real-world studies, the use of NOACs is noninferior to warfarin in Asians with atrial fibrillation irrespective of the NOAC type and dose.
Mode-Decomposed Equation Diagnosis for Atmospheric Blocking Development
Authors: Aikawa Takuya , Inatsu Masaru , Nakano Naoto , Iwano Tetsuya
Published: August 2019

This paper proposes a new method to identify atmospheric blocking development without the time filtering used in previous studies. A mode-decomposed vorticity equation is formulated from the principal components (PCs) of 500-hPa geopotential height by applying a new idea; the orthonormality of PCs allows any variable to be decomposed into a projection corresponding to the PCs. To test this, sectorial blocking episodes in Northern Hemisphere winter were identified by Barriopedro’s method. A blocking index was defined for each longitudinal range as the linear combination of the 10 largest PCs by means of the composite for the blocking episodes. Blocking development was diagnosed, in terms of the low modes of PC1–PC10 and the high modes of PC11–PC50. The results suggest that the intensification of blocking over the North Pacific and Eurasia is associated with nonlinear interaction among high modes, whereas the intensification (decay) of North Atlantic blocks is related mainly to enhanced nonlinear interaction among low-frequency (high-frequency) eddies. This main result is insensitive to the choice of definition for blocks and the choice of the mode separation boundary.
Impact of Vertical Wind Shear on Gravity Wave Propagation in the Land–Sea-Breeze Circulation at the Equator
Authors: Du Yu , Rotunno Richard , Zhang Fuqing
Published: August 2019

The impact of vertical wind shear on the land–sea-breeze circulation at the equator is explored using idealized 2D numerical simulations and a simple 2D linear analytical model. Both the idealized and linear analytical models indicate Doppler shifting and attenuation effects coexist under the effect of vertical wind shear for the propagation of gravity waves that characterize the land–sea-breeze circulation. Without a background wind, the idealized sea breeze has two ray paths of gravity waves that extend outward and upward from the coast. A uniform background wind causes a tilting of the two ray paths due to Doppler shifting. With vertical shear in the background wind, the downstream ray path of wave propagation can be rapidly attenuated near a certain level, whereas the upstream ray path is not attenuated and the amplitudes even increase with height. The downstream attenuation level is found to descend with increasing linear wind shear. The present analytical model establishes that the attenuation level corresponds to the critical level where the background wind is equal to the horizontal gravity wave phase speed. The upstream gravity wave ray path can propagate upward without attenuation as there is no critical level there.
Global Analysis of the Role of Terrestrial Water Storage in the Evapotranspiration Estimated from the Budyko Framework at Annual to Monthly Time Scales
Authors: Wu Chuanhao , Yeh Pat J.-F. , Wu Haichun , Hu Bill X. , Huang Guoru
Published: August 2019

Recent studies have extended the applicability of the Budyko framework from the long-term mean to annual or shorter time scales. However, the effects of water storage change ΔS on the overall water balance estimated from the Budyko models (BM) at annual-to-monthly time scales were less investigated, particularly at the continental or global scales, due to the lack of large-scale ΔS data. Here, based on a 25-yr (1984–2008) global gridded terrestrial water budget dataset and by using an analytical error-decomposition framework, we analyzed the effects of ΔS in evapotranspiration (ET) predicted from BM at both grid and basin scales under diverse climates for the annual, wet-seasonal, dry-seasonal, and monthly time scales. Results indicated that the BM underperforms in the short dry (wet) seasons of predominantly humid (dry) basins, with lower accuracy under more humid climates (at annual, dry-seasonal, and monthly scales) and under more arid climates (at wet-seasonal scale). When the effects of ΔS are incorporated into BM, improvements can be found mostly at annual and dry-seasonal scales, but not notable at wet-seasonal and monthly scales. The magnitudes of ΔS are positively correlated with the errors in BM-predicted ET for most global regions at annual and monthly scales, especially under arid climates. Under arid climates, the variability of ET prediction errors is controlled mainly by the ΔS variability at annual and monthly time scales. In contrast, under humid climates the effect of ΔS on ET prediction errors is generally limited, particularly at the wet-seasonal scale due to the more dominant influences of other climatic factors (precipitation and potential ET) and catchment responses (runoff).
A Barotropic Vorticity Budget for the Subtropical North Atlantic Based on Observations
Authors: Alexander-Astiz Le Bras Isabela , Sonnewald Maike , Toole John M.
Published: August 2019

To ground truth the large-scale dynamical balance of the North Atlantic subtropical gyre with observations, a barotropic vorticity budget is constructed in the ECCO state estimate and compared with hydrographic observations and wind stress data products. The hydrographic dataset at the center of this work is the A22 WOCE section, which lies along 66°W and creates a closed volume with the North and South American coasts to its west. The planetary vorticity flux across A22 is quantified, providing a metric for the net meridional flow in the western subtropical gyre. The wind stress forcing over the subtropical gyre to the west and east of the A22 section is calculated from several wind stress data products. These observational budget terms are found to be consistent with an approximate barotropic Sverdrup balance in the eastern subtropical gyre and are on the same order as budget terms in the ECCO state estimate. The ECCO vorticity budget is closed by bottom pressure torques in the western subtropical gyre, which is consistent with previous studies. In sum, the analysis provides observational ground truth for the North Atlantic subtropical vorticity balance and explores the seasonal variability of this balance for the first time using the ECCO state estimate. This balance is found to hold on monthly time scales in ECCO, suggesting that the integrated subtropical gyre responds to forcing through fast barotropic adjustment.
The Benefits and Costs of Low and High Degree of Automation
Authors: Tatasciore Monica , Bowden Vanessa K. , Visser Troy A. W. , Michailovs Steph I. C. , Loft Shayne
Published: August 2019

Objective

The objective of this study is to examine the effects of low and high degree of automation (DOA) on performance, subjective workload, situation awareness (SA), and return-to-manual control in simulated submarine track management.

Background

Theory and meta-analytic evidence suggest that as DOA increases, operator performance improves and workload decreases, but SA and return-to-manual control declines. Research also suggests that operators have particular difficulty regaining manual control if automation provides incorrect advice.

Method

Undergraduate student participants completed a submarine track management task that required them to track the position and behavior of contacts. Low DOA supported information acquisition and analysis, whereas high DOA recommended decisions. At a late stage in the task, automation was either unexpectedly removed or provided incorrect advice.

Results

Relative to no automation, low DOA moderately benefited performance but impaired SA and non-automated task performance. Relative to no automation and low DOA, high DOA benefited performance and lowered workload. High DOA did impair non-automated task performance compared with no automation, but this was equivalent to low DOA. Participants were able to return-to-manual control when they knew low or high DOA was disengaged, or when high DOA provided incorrect advice.

Conclusion

High DOA improved performance and lowered workload, at no additional cost to SA or return-to-manual performance when compared with low DOA.

Application

Designers should consider the likely level of uncertainty in the environment and the consequences of return-to-manual deficits before implementing low or high DOA.
A Review of Individual Operational Cognitive Readiness: Theory Development and Future Directions
Authors: Crameri Luke , Hettiarachchi Imali , Hanoun Samer
Published: August 2019

Objective

The aim of this paper is to provide a comprehensive and original review of the theoretical development of the individual operational cognitive readiness (OCR) theory.

Background

Cognitive readiness (CR) is a concept that has the potential to predict the performance of human individuals and teams prior to engaging in complex, dynamic, and resource-limited task environments. However, the current state of the literature is confusing and laborious, with heterogeneous views regarding the theoretical frameworks among leading researchers.

Method

This review (1) undertakes a systematic approach toward categorizing published CR literature into theoretical and measurement contributions across the different levels of CR, (2) carries a critical evaluation of the CR and OCR theoretical frameworks, and (3) provides directions for future research guided by gaps identified during the review process and other published literatures.

Results

Results from the categorization of published CR literature provide a new, valuable, synthesized CR library for researchers to consult to streamline their CR literature review process. Critical examination of the CR and OCR theoretical frameworks leads to positing that new components should be explored for OCR.

Conclusion

There are many possible directions for future research including evaluating domain-independent components of OCR and evaluating the relationship between biofeedback measures and performance in CR models.

Application

The Defense domain continues to be the focal application of CR. However, CR could be used by other application domains, such as sports and emergency services, that require their working personnel to engage in complex, uncertain, and dynamic task environments.
Safety Culture: An Integration of Existing Models and a Framework for Understanding Its Development
Authors: Bisbey Tiffany M. , Kilcullen Molly P. , Thomas Eric J. , Ottosen Madelene J. , Tsao KuoJen , Salas Eduardo
Published: August 2019

Objective

This study reviews theoretical models of organizational safety culture to uncover key factors in safety culture development.

Background

Research supports the important role of safety culture in organizations, but theoretical progress has been stunted by a disjointed literature base. It is currently unclear how different elements of an organizational system function to influence safety culture, limiting the practical utility of important research findings.

Method

We reviewed existing models of safety culture and categorized model dimensions by the proposed function they serve in safety culture development. We advance a framework grounded in theory on organizational culture, social identity, and social learning to facilitate convergence toward a unified approach to studying and supporting safety culture.

Results

Safety culture is a relatively stable social construct, gradually shaped over time by multilevel influences. We identify seven enabling factors that create conditions allowing employees to adopt safety culture values, assumptions, and norms; and four behaviors used to enact them. The consequences of these enacting behaviors provide feedback that may reinforce or revise held values, assumptions, and norms.

Conclusion

This framework synthesizes information across fragmented conceptualizations to clearly depict the dynamic nature of safety culture and specific drivers of its development. We suggest that safety culture development may depend on employee learning from behavioral outcomes, conducive enabling factors, and consistency over time.

Application

This framework guides efforts to understand and develop safety culture in practice and lends researchers a foundation for advancing theory on the complex, dynamic processes involved in safety culture development.
An intuitive, application-based, simulation-driven approach to teaching probability and random processes
Authors: Sheikh Waseem
Published: August 2019

Probability and random processes is considered by students to be conceptually one of the most difficult subjects in the undergraduate electrical and computer engineering curriculum. There are numerous reasons for this difficulty encountered by the students. First off, humans are not innately good at probabilistic intuition. Traditionally, this subject has been introduced in a very abstract manner without emphasis on real-world applications from electrical and computer engineering discipline. In addition, extensive use of interactive simulation and visualization tools, offering an alternative way of developing probabilistic intuition, is usually missing from traditional course offerings. This paper presents a unique pedagogical approach to teaching an introductory probability course offered to electrical and computer engineering juniors. The salient features of the proposed pedagogical approach include more emphasis on real-world electrical and computer engineering problems that show the applications of abstract probabilistic concepts; extensive hands-on and interactive MATLAB® simulations of real-world electrical and computer engineering problems that are tightly integrated into the curriculum; highlighting the frequentist approach to build probabilistic intuition using simulations; concrete examples showing how naive probabilistic intuition can be erroneous and how to develop correct probabilistic intuition based on systematically modeling, simulating, and analyzing a problem; and application-based simulations driving the abstract theory rather than the other way around. This pedagogical approach was implemented in a course offered to electrical and computer engineering undergraduates at Purdue University Northwest. The paper presents a concrete example illustrating how the salient features of the proposed pedagogical approach were implemented as part of this course and student data from the courses to validate the efficacy of the proposed approach.
Health Care Crisis by the Numbers
Authors: Himmelstein David U. , Woolhandler Steffie , Fauke Clare
Published: August 2019

We summarize recent data on health and health care in the United States. Many millions suffer financial distress due to medical bills and forego needed care because of costs. Pay-for-performance programs have failed to achieve the results promised and in some cases have backfired. Health care firms expend huge amounts on marketing that provides no benefit to patients. Millions of health care workers, particularly women of color, are so poorly paid that they live in poverty, and gender-based pay inequities remain common in the health sector. Polls continue to show strong popular support for a single-payer reform, but politicians continue to resist it.