bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stem Cells in Primary Sjögren’s Syndrome: Prospective and Challenges
Authors: Chen Weiqian , Yu Ye , Ma Jilin , Olsen Nancy , Lin Jin
Published: September 2018

Primary Sjögren’s syndrome (pSS) is a chronic systemic inflammatory autoimmune disease characterized by lymphocytic infiltrates in exocrine glands. Current approaches do not control harmful autoimmune attacks or prevent irreversible damage and have considerable side effects. Mesenchymal stem cells (MSCs) have been effective in the treatment of several autoimmune diseases. The objective of this review is to illustrate the potential therapeutic role of MSCs in pSS. We summarize the recent advances in what is known about their immunomodulatory function and therapeutic applications in pSS. MSC transfusion can suppress autoimmunity and restore salivary gland secretory function in mouse models and patients with pSS by inducing regulatory T cells, suppressing Th1, Th17, and T follicular helper cell responses. In addition, MSCs can differentiate into salivary epithelial cells, presenting an option as a suitable alternative treatment. We also discuss current bioengineering methods which improve functions of MSCs for pSS. However, there remain many challenges to overcome before their wide clinical application.
Mesalazine for People with Diverticular Disease: A Systematic Review of Randomized Controlled Trials
Authors: Iannone Andrea , Ruospo Marinella , Wong Germaine , Barone Michele , Principi Mariabeatrice , Di Leo Alfredo , Strippoli Giovanni F. M.
Published: September 2018

Background. Diverticular disease treatment is limited to fibres, antibiotics, and surgery. There is conflicting evidence on mesalazine benefits and harms. Aim. We systematically reviewed current evidence on benefits and harms of mesalazine versus all other treatments in people with diverticular disease. Methods. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov for studies published to July 2018. We estimated risk ratios (RR) for dichotomous outcomes (disease remission/recurrence, acute diverticulitis in symptomatic uncomplicated diverticular disease, need for surgery/hospitalization, all-cause/disease-related mortality, adverse events), mean differences (MD) or standardized MD (SMD) for continuous outcomes (quality of life, symptoms score, time to recurrence/remission), and their 95% confidence intervals (CI) using random-effects models. We quantified heterogeneity by Chi2 and I2 tests. We performed subgroup analyses by disease subtype, comparator, follow-up duration, mesalazine dose, and mode of administration. Results. We identified 13 randomized trials (n=3028 participants). There was a higher likelihood of disease remission with mesalazine than controls in acute uncomplicated diverticulitis (1 trial, 81 participants, RR=2.67, 95%CI=1.05-6.79), but not in symptomatic uncomplicated diverticular disease (1 trial, 123 participants, RR=1.04, 95%CI=0.81-1.34). There was a lower likelihood of disease recurrence with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 216 participants, RR=0.52, 95%CI=0.28-0.97), but not in acute uncomplicated diverticulitis (7 trials, 2196 participants, RR=0.90, 95%CI=0.61-1.33). There was no difference in the likelihood of developing acute diverticulitis in symptomatic uncomplicated diverticular disease between the two groups (3 trials, 484 participants, RR=0.26, 95%CI=0.06-1.20). There was a higher global symptoms score reduction with mesalazine than controls in symptomatic uncomplicated diverticular disease (2 trials, 326 participants, SMD=-1.01, 95%CI=-1.51,-0.52) and acute uncomplicated diverticulitis (2 trials, 153 participants, SMD=-0.56, 95%CI=-0.88,-0.24). Conclusions. Mesalazine may reduce recurrences in symptomatic uncomplicated diverticular disease. There is uncertainty on the effect of mesalazine in achieving diverticular disease remission. Mesalazine may not prevent acute diverticulitis in symptomatic uncomplicated diverticular disease.
Health-Related Quality of Life and Associated Factors among Women on Antiretroviral Therapy in Health Facilities of Jimma Town, Southwest Ethiopia
Authors: Abebe Weldsilase Yetnayet , Likka Melaku Haile , Wakayo Tolossa , Gerbaba Mulusew
Published: September 2018

Background. This study examined health-related quality of life and associated factors among HIV positive women receiving antiretroviral therapy in health facilities of Jimma town. Methods. A cross-sectional study was conducted, and consecutive sampling technique was employed to select 377 HIV positive women who were on antiretroviral therapy. Quality of life was measured using WHOQOL-BREF tool. Descriptive statistics, bivariate, and multivariable logistic regression analyses were performed. P values < 0.05 and adjusted odds ratio with 95% of confidence interval were used to determine statistical significance and report associations between the quality of life and independent variables. Results. Among the sampled participants, 344 were interviewed, yielding 91% of response rate. The mean ± standard deviation age of the respondents was 34.07 ± 8.76 years and 80.5% of them were urban dwellers. The proportion of women reporting good health-related quality of life was found to be 46.5%. Specific to each domain, the mean ± standard deviation of level of independence domain was the highest (14.08 ± 3.07) followed by physical (13.46 ± 2.95), social relationships (13.27 ± 3.91), psychological (12.97 ± 2.47), environmental (12.94 ± 3.25), and spiritual (12.39 ± 2.84) domains. Good social support (AOR: 4.99; 95% CI: [2.88, 8.34]), higher wealth status (AOR: 1.85; 95% CI: [1.02, 3.39]), and being on antiretroviral therapy for shorter duration (AOR: 1.85; 95% CI [1.14, 3.03]) were independently associated with better overall health-related quality of life among the participants. Conclusions. The study demonstrated high proportion of HIV positive women on ART had poor health-related quality of life which was affected by wealth index, social support, and duration on antiretroviral therapy.
Bricks and Concrete Wastes as Coarse and Fine Aggregates in Sustainable Mortars
Authors: Mobili Alessandra , Giosuè Chiara , Corinaldesi Valeria , Tittarelli Francesca
Published: September 2018

The total substitution by volume of natural coarse calcareous aggregate by coarse recycled brick aggregate (RBA) and coarse recycled concrete aggregate (RCA) has been investigated to produce more sustainable and environment‐friendly mortars. Aggregates were also partially substituted by their fines at 12.5% by volume. Mortars have been tested in terms of mechanical, microstructural, and durability properties. Results show that it is feasible to replace a natural calcareous aggregate entirely by recycled aggregates. In particular, the obtained mortars, even if more porous and more prone to the water capillary absorption than that manufactured with natural aggregates, result in less stiffness and thus are less subjected to crack formation, more permeable to water vapour, and less susceptible to sulphate attack.
Mining Connected Vehicle Data for Beneficial Patterns in Dubai Taxi Operations
Authors: Bridgelall Raj , Lu Pan , Tolliver Denver D. , Xu Tai
Published: September 2018

On-demand shared mobility services such as Uber and microtransit are steadily penetrating the worldwide market for traditional dispatched taxi services. Hence, taxi companies are seeking ways to compete. This study mined large-scale mobility data from connected taxis to discover beneficial patterns that may inform strategies to improve dispatch taxi business. It is not practical to manually clean and filter large-scale mobility data that contains GPS information. Therefore, this research contributes and demonstrates an automated method of data cleaning and filtering that is suitable for such types of datasets. The cleaning method defines three filter variables and applies a layered statistical filtering technique to eliminate outlier records that do not contribute to distributions that match expected theoretical distributions of the variables. Chi-squared statistical tests evaluate the quality of the cleaned data by comparing the distribution of the three variables with their expected distributions. The overall cleaning method removed approximately 5% of the data, which consisted of errors that were obvious and others that were poor quality outliers. Subsequently, mining the cleaned data revealed that trip production in Dubai peaks for the case when only the same two drivers operate the same taxi. This finding would not have been possible without access to proprietary data that contains unique identifiers for both drivers and taxis. Datasets that identify individual drivers are not publicly available.
To Cycle or Fight—CDK4/6 Inhibitors at the Crossroads of Anticancer Immunity
Authors: Ameratunga Malaka , Kipps Emma , Okines Alicia F.C. , Lopez Juanita S.
Published: September 2018

Dysregulation of cell division resulting in aberrant cell proliferation is a key hallmark of cancer, making it a rational and important target for innovative anticancer drug development. Three selective cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are FDA and European Medicines Agency (EMA) approved for hormone receptor–positive/HER2-negative advanced breast cancer. A major emerging appreciation is that these inhibitors not only are cytostatic, but also play critical roles in the interaction between tumor cells and the host immune response. However, to trigger an effective immune response, lymphocytes must also proliferate. This review aims to assimilate our emerging understanding on the role of CDK4/6 inhibitors in cell-cycle control, as well as their biological effect on T cells and other key immune cells, and the confluence of preclinical evidence of augmentation of anticancer immunity by these drugs. We aim to provide a framework for understanding the role of the cell cycle in anticancer immunity, discussing ongoing clinical trials evaluating this concept and challenges for developing rational combinations with immunotherapy.
Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer
Authors: Dagogo-Jack Ibiayi , Martinez Pablo , Yeap Beow Y. , Ambrogio Chiara , Ferris Lorin A. , Lydon Christine , Nguyen Tom , Jessop Nicholas A. , Iafrate A. John , Johnson Bruce E. , Lennerz Jochen K. , Shaw Alice T. , Awad Mark M.
Published: September 2018

Purpose:

BRAF mutations are divided into functional classes distinguished by signaling mechanism and kinase activity: V600-mutant kinase-activating monomers (class I), kinase-activating dimers (class II), and kinase-inactivating heterodimers (class III). The relationship between functional class and disease characteristics in BRAF-mutant non–small cell lung cancer (NSCLC) has not been fully explored.

Experimental Design:

We performed a retrospective analysis of BRAF-mutant NSCLCs treated at 2 institutions from 2005 to 2017 to determine clinicopathologic characteristics, progression-free survival (PFS) on chemotherapy, and overall survival (OS).

Results:

We identified 236 patients with BRAF-mutant NSCLC (n = 107 class I, n = 75 class II, and n = 54 class III). Patients with class II or III mutations were more likely to have brain metastases (P ≤ 0.01) and RAS coalterations (P ≤ 0.001) than class I. Compared with class I, PFS on chemotherapy was shorter for class II (P = 0.069) and class III (P = 0.034). OS was shorter for class II and III (class I, 40.1 months; class II, 13.9 months; and class III, 15.6 months; I vs. II, P < 0.001; I vs. III, P = 0.023); however, this difference was driven by fewer extrathoracic metastases and higher use of targeted therapies in class I patients. When patients treated with targeted therapy and those with thoracic-only metastases were excluded, there was no difference in OS across the 3 classes.

Conclusions:

BRAF-mutant NSCLC is a heterogeneous disease that encompasses 3 distinct functional classes. Classes II and III have more aggressive clinical features leading to less favorable outcomes. The distinct biological characteristics of class II and III tumors suggest that class-specific therapies may be necessary to effectively target these molecular subsets.
Establishment and Genetic Landscape of Precancer Cell Model Systems from the Head and Neck Mucosal Lining
Authors: de Boer D. Vicky , Brink Arjen , Buijze Marijke , Stigter-van Walsum Marijke , Hunter Keith D. , Ylstra Bauke , Bloemena Elisabeth , Leemans C. René , Brakenhoff Ruud H.
Published: September 2018

Head and neck squamous cell carcinomas (HNSCC) develop in fields of genetically altered cells. These fields are often dysplastic and a subset can be recognized as (erythro)leukoplakia, but most are macroscopically invisible. There is a lack of adequate treatment options to eradicate these fields, whereas they underlie the development of primary tumors as well as part of the local relapses. Unfortunately, there are almost no representative cellular models available to identify suitable treatment options. To this end, clinical biopsy specimens (n = 98) were cultured from normal appearing mucosa of the surgical margins of patients with primary HNSCCs (n = 32) to generate precancer cell culture models. This collection was extended with six previously established precancer cell cultures. Genetic analysis was performed on cultures with an extended life span (≥20 population doublings), the previously established cultures, and some randomly selected cultures. In total, cancer-associated changes were detected in 18 out of 34 (53%) cultures analyzed, which appeared to be independent of life span. A variety of genetic changes were identified, including somatic mutations as well as chromosomal copy-number aberrations (CNA). Loss of CDKN2A/p16Ink4A and mutations in TP53/p53 were most prominent. Remarkably, in some of these precancer cell cultures only chromosomal CNAs were detected, and none of the frequently occurring driver mutations.

Implications:

The precancer cell cultures, characterized herein, form a representative collection of field models that can be exploited to identify and validate new therapeutic strategies to prevent primary HNSCCs and local relapses.
Conservation of Ovary-Specific Genes, Foxl2, Aromatase, and Rspo1, in the Common Indian Garden Lizard, Calotes versicolor, That Lacks Chromosomal or Temperature-Dependent Sex Determination
Authors: Priyanka  , Tripathi Vidisha , Raman Rajiva
Published: September 2018

Foxl2,Rspo1, and Aromatase are genes important in the ovary developmental pathway in mammals and birds. Here, we show their presence in the lizard, Calotes versicolor, which is known to lack a chromosomal as well as a temperature-dependent mode of sex determination and has an indeterminate, bipotential gonad throughout embryonic development. The expression of the 3 genes, as well as that of CvSox9 and Wnt4 - the known testis and ovary pathway genes - was studied by RT-PCR and whole tissue RNA in situ hybridization (WRISH) on the developing mesonephros gonadal complex (MGC). The expression of all 3 genes was initiated in the gonad shortly after its evagination from the mesonephros (day 5 onwards). CvFoxl2 generally was expressed in those MGCs in which CvSox9 was either not expressed or lowly expressed and vice versa. On the other hand, CvArom was expressed rather sporadically and randomly, showing no association with CvFoxl2, CvRspo1, or CvSox9, though in later stages WRISH preparations showed its coincidence with CvWnt4. CvRspo1 was expressed in almost all embryos right from day 5. Immunofluorescence localization of Rspo1 and Foxl2 proteins showed their presence in the gonads from day 10 onwards, and by day 25 it was primarily confined to the cortex but away from the coelomic epithelium of the gonadal cortex. Apparently both proteins were localized in the pregranulosa cells, Rspo1 in the cytoplasm and Foxl2 in the nucleus. Thus, it is clear that both CvFoxl2 and CvRspo1 are active in ovary formation, but whether they are expressed in the same or different cells is unknown. Though the transcription pattern of CvArom remains circumspect for its role in differentiation of the ovary, earlier evidence on aromatase inhibitor-induced reversal to the male sex indicates its importance in ovary function.
High-Salt Diet Causes Expansion of the Lymphatic Network and Increased Lymph Flow in Skin and Muscle of Rats
Authors: Karlsen Tine V. , Nikpey Elham , Han Jianhua , Reikvam Tore , Rakova Natalia , Castorena-Gonzalez Jorge A. , Davis Michael J. , Titze Jens M. , Tenstad Olav , Wiig Helge
Published: September 2018

Objective—

A commonly accepted pivotal mechanism in fluid volume and blood pressure regulation is the parallel relationship between body Na
+
and extracellular fluid content. Several recent studies have, however, shown that a considerable amount of Na
+
can be retained in skin without commensurate water retention. Here, we asked whether a salt accumulation shown to result in VEGF (vascular endothelial growth factor)-C secretion and lymphangiogenesis had any influence on lymphatic function.

Approach and Results—

By optical imaging of macromolecular tracer washout in skin, we found that salt accumulation resulted in an increase in lymph flow of 26% that was noticeable only after including an overnight recording period. Surprisingly, lymph flow in skeletal muscle recorded with a new positron emission tomography/computed tomography method was also increased after salt exposure. The transcapillary filtration was unaffected by the high-salt diet and deoxycorticosterone-salt treatment, suggesting that the capillary barrier was not influenced by the salt accumulation. A significant reduction in lymph flow after depletion of macrophages/monocytes by clodronate suggests these cells are involved in the observed lymph flow response, together with collecting vessels shown here to enhance their contraction frequency as a response to extracellular Na
+
.

Conclusions—

The observed changes in lymph flow suggest that the lymphatics may influence long-term regulation of tissue fluid balance during salt accumulation by contributing to fluid homeostasis in skin and muscle. Our studies identify lymph clearance as a potential disease-modifying factor that might be targeted in conditions characterized by salt accumulation like chronic kidney disease and salt-sensitive hypertension.
Factor XII Activation Promotes Platelet Consumption in the Presence of Bacterial-Type Long-Chain Polyphosphate In Vitro and In Vivo
Authors: Zilberman-Rudenko Jevgenia , Reitsma Stéphanie E. , Puy Cristina , Rigg Rachel A. , Smith Stephanie A. , Tucker Erik I. , Silasi Robert , Merkulova Alona , McCrae Keith R. , Maas Coen , Urbanus Rolf T. , Gailani David , Morrissey James H. , Gruber András , Lupu Florea , Schmaier Alvin H. , McCarty Owen J.T.
Published: September 2018

Objective—

Terminal complications of bacterial sepsis include development of disseminated intravascular consumptive coagulopathy. Bacterial constituents, including long-chain polyphosphates (polyP), have been shown to activate the contact pathway of coagulation in plasma. Recent work shows that activation of the contact pathway in flowing whole blood promotes thrombin generation and platelet activation and consumption distal to thrombus formation ex vivo and in vivo. Here, we sought to determine whether presence of long-chain polyP or bacteria in the bloodstream promotes platelet activation and consumption in a coagulation factor (F)XII-dependent manner.

Approach and Results—

Long-chain polyP promoted platelet P-selectin expression, microaggregate formation, and platelet consumption in flowing whole blood in a contact activation pathway-dependent manner. Moreover, long-chain polyP promoted local fibrin formation on collagen under shear flow in a FXI-dependent manner. Distal to the site of thrombus formation, platelet consumption was dramatically enhanced in the presence of long-chain polyP in the blood flow in a FXI- and FXII-dependent manner. In a murine model, long-chain polyP promoted platelet deposition and fibrin generation in lungs in a FXII-dependent manner. In a nonhuman primate model of bacterial sepsis, pre-treatment of animals with an antibody blocking FXI activation by FXIIa reduced lethal dose
100
Staphylococcus aureus
–induced platelet and fibrinogen consumption.

Conclusions—

This study demonstrates that bacterial-type long-chain polyP promotes platelet activation in a FXII-dependent manner in flowing blood, which may contribute to sepsis-associated thrombotic processes, consumptive coagulopathy, and thrombocytopenia.
Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Subsequent Risk of Emergency Department Visits and Hospitalizations for Atrial Fibrillation
Authors: Hirayama Atsushi , Goto Tadahiro , Shimada Yuichi J. , Faridi Mohammad Kamal , Camargo Carlos A. , Hasegawa Kohei
Published: September 2018

Background

Although emerging evidence has suggested the relationship of chronic obstructive pulmonary disease with atrial fibrillation (AF), little is known about whether acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of repeated AF-related healthcare utilization.

Methods

This is a self-controlled case series study using the population-based emergency department (ED) and inpatient databases of 5 US states from 2007 through 2012. Among patients with existing AF, we identified patients with an AECOPD hospitalization and at least 1 ED visit or hospitalization for AF during the observation period. We constructed conditional Poisson regression models to compare the rate of AF-related ED visits or hospitalizations during sequential 90-day periods after the AECOPD hospitalization, with pre-AECOPD days 1 to 90 as the reference.

Results

We analyzed 944 patients who were hospitalized for AECOPD and had an ED visit or hospitalization for AF during a 450-day period. The median age was 77 years, and 41% were men. Compared with the reference period, the rate of AF-related ED visits or hospitalizations significantly increased in the post-AECOPD days 1 to 90 (7.3 versus 14.1 per 100 person-months; rate ratio, 1.93; 95% CI, 1.63–2.29;
P
<0.001). Then, the rate decreased to the reference level in the post-AECOPD days 91 to 180 (7.5 per 100 person-months; rate ratio, 1.03; 95% CI, 0.85–1.25;
P
=0.77) and remained at the reference level during post-AECOPD days 181 to 270 (rate ratio, 0.84; 95% CI, 0.68–1.03;
P
=0.09) and days 271 to 360 (rate ratio, 0.90; 95% CI, 0.73–1.10;
P
=0.29). These temporal associations persisted with stratification by age, sex, and season.

Conclusions

Among patients with existing AF, AECOPD was associated with a higher risk of AF-related ED visit or hospitalization in the first 90-day post-AECOPD period.
Left Ventricular Systolic Longitudinal Function as Predictor of Outcome in Patients With Sepsis
Authors: Palmieri Vittorio , Innocenti Francesca , Guzzo Aurelia , Guerrini Elisa , Vignaroli Damiano , Pini Riccardo
Published: September 2018

Background—

In sepsis, whether the assessment of left ventricular global longitudinal systolic strain (GLS) is feasible and prognostically relevant remains controversial.

Methods and Results—

Consecutive patients admitted to a high-dependency observational unit with sepsis or septic shock were evaluated. Left ventricular ejection fraction (EF) by planimetry and peak GLS by 2D speckle tracking were available at admission in 115 of 149 (77%) patients. Compared with patients included in the study, those excluded (n=34, 23%) showed higher proportion of chronic obstructive pulmonary disease (
P
<0.01), but with comparable clinical characteristics and mortality rates. GLS showed lowest variability for low EF and highest for higher EF. By day-28 follow-up, all-cause mortality was 30% (n=34 and n=19 within 7 days from hospitalization). GLS and EF were both more abnormal in deceased than in those alive by day-28 follow-up (both
P
<0.05, findings consistent using day-7 follow-up data). GLS showed a borderline relationship with mortality by day-28 follow-up (hazard ratio 1.16/%,
P
=0.05), whereas EF did not (hazard ratio 0.99/%,
P
=0.63) accounting for age; the lack of association of all-cause mortality with EF was consistent at day-7 follow-up (hazard ratio 0.94/%,
P
=0.9), whereas more abnormal GLS correlated significantly with higher mortality rate (hazard ratio 1.30/%,
P
=0.03) independent to age.

Conclusions—

In patients with sepsis assisted in a high-dependency observational unit, feasibility of assessments of left ventricular EF and GLS within 24 h from the hospitalization was acceptable and EF showed no prognostic relevance, whereas GLS showed a correlation with mortality rate potentially relevant in shorter more than in longer follow-ups.
Effect of Cardiac Resynchronization Therapy on Exercise-Induced Pulmonary Hypertension and Right Ventricular-Arterial Coupling
Authors: Martens Pieter , Verbrugge Frederik H. , Bertrand Philippe B. , Verhaert David , Vandervoort Pieter , Dupont Matthias , Tang W.H. Wilson , Janssens Stefan , Mullens Wilfried
Published: September 2018

Background

Acute and chronic effects of cardiac resynchronization therapy (CRT) on pulmonary pressures, right ventricular function, and ventricular-vascular coupling during exercise are insufficiently understood. Yet, these factors are strongly associated with functional status and outcome.

Methods and Results

Heart failure patients with reduced ejection fraction indicated for CRT were prospectively included to undergo exercise echocardiography simultaneously with cardiopulmonary exercise testing before (pre_CRT), 1 day after (post_CRT), and 6 months (post6_CRT) after CRT implant. Right ventricular-arterial coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (SPAP) ratio. A total of 31 heart failure patients with reduced ejection fraction (age=66±13 years) were prospectively included. CRT resulted in an immediate reduction in rest SPAP (pre_CRT=32±16 versus post_CRT=23±16 mm Hg;
P
=0.006) and rest effective regurgitant orifice (pre_CRT=0.32±0.1 versus post_CRT=0.18±0.2;
P
=0.001) without changes in exercise mitral regurgitation or exercise SPAP indexed for cardiac output. Six months after CRT, in parallel with left ventricular reverse remodeling and a reduction in exercise mitral regurgitation and exercise E/e′ ratio, the exercise SPAP/cardiac output significantly improved (post_CRT=5.6±3.1 versus post6_CRT=4.3±2.9 mm Hg·L
−1
·min
−1
;
P
=0.039), which was also illustrated by a reduced slope of ΔSPAP/Δcardiac output (post_CRT=5.2±3.7 versus post6_CRT=2.9±2.7 mm Hg·L
−1
·min
−1
;
P
=0.002). CRT did not result in an acute or chronic effect on TAPSE or TAPSE/SPAP ratio at rest. However, exercise revealed the presence of right ventricular-arterial uncoupling which was not affected by an acute CRT effect (
P
=0.396) but only improved by a chronic CRT effect (
P
<0.001; TAPSE/SPAP ratio: pre_CRT= 0.39±0.6 mm/mm Hg; post_CRT=0.42±0.5 mm/mm Hg; post6_CRT =0.84±0.12 mm/mm Hg). Of all exercise echocardiography variables, the TAPSE/SPAP ratio demonstrated the strongest correlation with V
o
2
peak (
r
=0.475), VE/V
co
2
(
r
=−0.585), and workload (
r
=0.476) during cardiopulmonary exercise testing (
P
<0.05 all). Multivariate predictors affecting exercise ventricular-arterial coupling after CRT included metrics of residual exercise mitral regurgitation and systolic and diastolic left ventricular function.

Conclusions

Chronic CRT beneficially influences pulmonary pressures and right ventricular-arterial coupling during exercise, which strongly relates to functional status. These findings are mechanistically linked to reverse remodeling with improved interventricular dependence and reduction in exercise mitral regurgitation.
Cancellation of the Cardiac Catheterization Lab After Activation for ST-Segment–Elevation Myocardial Infarction
Authors: Lange David C. , Conte Stanley , Pappas-Block Effie , Hildebrandt David , Nakamura Mamoo , Makkar Raj , Kar Saibal , Torbati Sam , Geiderman Joel , McNeil Nathan , Cercek Bojan , Tabak Steven W. , Rokos Ivan , Henry Timothy D.
Published: September 2018

Background:

Prehospital ECG-based cardiac catheterization laboratory (CCL) activation for ST-segment–elevation myocardial infarction reduces door-to-balloon times, but CCL cancellations (CCL
X
) remain a challenging problem. We examined the reasons for CCL
X
, clinical characteristics, and outcomes of patients presenting as ST-segment–elevation myocardial infarction activations who receive emergent coronary angiography (EA) compared with CCL
X
.

Methods and Results:

We reviewed all consecutive CCL activations between January 1, 2012, and December 31, 2014 (n=1332). Data were analyzed comparing 2 groups stratified as EA (n=466) versus CCL
X
(n=866; 65%). Reasons for CCL
X
included bundle branch block (21%), poor-quality prehospital ECG (18%), non–ST-segment–elevation myocardial infarction ST changes (18%), repolarization abnormality (13%), and arrhythmia (8%). A multivariate logistic regression model using age, peak troponin, and initial ECG findings had a high discriminatory value for determining EA versus CCL
X
(C statistic, 0.985). CCL
X
subjects were older and more likely to be women, have prior coronary artery bypass grafting, or a paced rhythm (
P
<0.0001 for all). All-cause mortality did not differ between groups at 1 year or during the study period (mean follow-up, 2.186±1.167 years; 15.8% EA versus 16.2% CCL
X
;
P
=0.9377). Cardiac death was higher in the EA group (11.8% versus 3.0%;
P
<0.0001). After adjusting for clinical variables associated with survival, CCL
X
was associated with an increased risk for all-cause mortality during the study period (hazard ratio, 1.82; 95% CI, 1.28–2.59;
P
=0.0009).

Conclusions:

In this study, prehospital ECG without overreading or transmission lead to frequent CCL
X
. CCL
X
subjects differ with regard to age, sex, risk factors, and comorbidities. However, CCL
X
patients represent a high-risk population, with frequently positive cardiac enzymes and similar short- and long-term mortality compared with EA. Further studies are needed to determine how quality improvement initiatives can lower the rates of CCL
X
and influence clinical outcomes.
Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans
Authors: Yamashiro Yoshito , Thang Bui Quoc , Shin Seung Jae , Lino Caroline Antunes , Nakamura Tomoyuki , Kim Jungsil , Sugiyama Kaori , Tokunaga Chiho , Sakamoto Hiroaki , Osaka Motoo , Davis Elaine C. , Wagenseil Jessica E. , Hiramatsu Yuji , Yanagisawa Hiromi
Published: September 2018

Rationale:

Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated.

Objective:

The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy.

Methods and Results:

We used a mouse model of postnatal ascending aortic aneurysms (

Fbln4
SMKO

; termed
SMKO
[SMC-specific knockout]), in which deletion of
Fbln4
(fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in
SMKO
ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of
Fbln4
sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of
Thbs1
in
SMKO
mice prevented the aneurysm formation in ≈80% of
DKO
(SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in
DKO
aortas, and mechanical testing showed that structural and material properties of
DKO
aortas were markedly improved.

Conclusions:

Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.
Hypertension Treatment Effects on Orthostatic Hypotension and Its Relationship With Cardiovascular Disease
Authors: Juraschek Stephen P. , Appel Lawrence J. , Miller Edgar R. , Mukamal Kenneth J. , Lipsitz Lewis A.
Published: September 2018

Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102–107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15–2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09–3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80–13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21–4.30), and any CVD event (HR, 2.12; 95% CI, 1.12–3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.
Impact of Obstructive Sleep Apnea on Platelet Function Profiles in Patients With Acute Coronary Syndrome Taking Dual Antiplatelet Therapy
Authors: Gong Wei , Wang Xiao , Fan Jingyao , Nie Shaoping , Wei Yongxiang
Published: September 2018

Background

Obstructive sleep apnea (
OSA
) is a novel risk factor for acute coronary syndrome (
ACS
). Several studies have shown
OSA
to be associated with induced platelet reactivity. However, whether
OSA
have effects on platelet function profiles in
ACS
patients taking dual antiplatelet therapy remains unexplored.

Methods and Results

This was a cross‐sectional observational study, in which
ACS
patients taking maintenance aspirin and clopidogrel therapy were included.
OSA
was defined as an apnea‐hypopnea index ≥15 events/hour. The inhibitory rate of arachidonic acid or adenosine diphosphate pathway were assessed with thrombelastography and defined patients with high residual on‐treatment platelet reactivity. Platelet indices were obtained from routine analysis of blood samples using an automated blood cell counter. A total of 127
ACS
patients taking dual antiplatelet therapy were analyzed. Platelet volume indices, including mean platelet volume and platelet large cell ratio, were significantly increased in patients with
OSA
. Patients with
OSA
(n=68) had significantly lower inhibitory rate of adenosine diphosphate receptor pathway (
P
=0.028) compared with those without (n=59). After adjustment for potential confounders, patients with
OSA
were more likely to have high residual on‐treatment platelet reactivity after clopidogrel therapy (adjusted odds ratio: 3.25, 95% confidence interval: 1.19–8.87,
P
=0.021).

Conclusions

In
ACS
patients taking dual antiplatelet therapy,
OSA
is associated with an increased level of platelet volume indices, reduced clopidogrel‐induced antiplatelet effects and a greater prevalence of high residual on‐treatment platelet reactivity.
Effect of Fetal Growth on 1‐Year Mortality in Neonates With Critical Congenital Heart Disease
Authors: Steurer Martina A. , Baer Rebecca J. , Burke Edmund , Peyvandi Shabnam , Oltman Scott , Chambers Christina D. , Norton Mary E. , Rand Larry , Rajagopal Satish , Ryckman Kelli K. , Feuer Sky K. , Liang Liang , Paynter Randi A. , McCarthy Molly , Moon‐Grady Anita J. , Keller Roberta L. , Jelliffe‐Pawlowski Laura L.
Published: September 2018

Background

Infants with critical congenital heart disease (
CCHD
) are more likely to be small for gestational age (GA). It is unclear how this affects mortality. The authors investigated the effect of birth weight
Z
score on 1‐year mortality separately in preterm (GA <37 weeks), early‐term (GA 37–38 weeks), and full‐term (GA 39–42 weeks) infants with
CCHD
.

Methods and Results

Live‐born infants with
CCHD
and
GA
22 to 42 weeks born in California 2007–2012 were included in the analysis. The primary predictor was
Z
score for birth weight and the primary outcome was 1‐year mortality. Multivariable logistic regression was used. Results are presented as adjusted odds ratios and 95% confidence intervals (
CIs
). The authors identified 6903 infants with
CCHD
. For preterm and full‐term infants, only a
Z
score for birth weight <−2 was associated with increased mortality compared with the reference group (
Z
score 0–0.5, adjusted odds ratio, 2.15 [95%
CI
, 1.1–4.21] and adjusted odds ratio, 3.93 [95%
CI
, 2.32–6.68], respectively). In contrast, in early‐term infants, the adjusted odds ratios for
Z
scores <−2, −2 to −1, and −1 to −0.5 were 3.42 (95%
CI
, 1.93–6.04), 1.78 (95%
CI
, 1.12–2.83), and 2.03 (95%
CI
, 1.27–3.23), respectively, versus the reference group.

Conclusions

GA
seems to modify the effect of birth weight
Z
score on mortality in infants with
CCHD
. In preterm and full‐term infants, only the most severe small‐for‐GA infants (
Z
score <−2) were at increased risk for mortality, while, in early‐term infants, the risk extended to mild to moderate small‐for‐GA infants (
Z
score <−0.5). This information helps to identify high‐risk infants and is useful for surgical planning.
Rising China and Global Investment Governance: An Overview of Prospects and Challenges
Authors: Pathirana Dilini
Published: September 2018

International investment is one of the fields of global governance that is likely to be affected by China’s rise as a global superpower in general, and its rise as a global investor in particular. It has become manifest by China’s leadership in forming of the G20 Guiding Principles for Global Investment Policymaking and in establishing the Asian Infrastructure Investment Bank, while signaling the country’s growing capacity to influence global investment governance. However, China’s aspiration to steer global investment governance is being hindered by the increased backlash against globalisation and the investment treaty regime, as well as the rapid growth of Chinese investments. At the same time that protectionist measures aimed at Chinese investments are on the rise, the Belt and Road Initiative is underway, which will increase Chinese desire to safeguard the interests of Chinese investors. Consequently, it is possible that a Beijing-based pole in global investment governance could emerge, just as reforms are underway to address the legitimacy crisis in the regime.
Description and molecular phylogeny of Axinella nayaritensis n. sp. (Porifera: Axinellida) from East Pacific and remarks about the polyphyly of the genus Axinella
Authors: CARBALLO JOSE LUIS , BAUTISTA-GUERRERO ERIC , CRUZ-BARRAZA JOSE ANTONIO
Published: September 2018

Axinella nayaritensis n. sp. is a typical species of the genus Axinella in spiculation (oxeas and styles), skeletal arrangement (axial condensation from which radiate an extra-axial plumoreticulated skeleton), and external form (arborescent). The new species is orange, branching, up to 25 cm in height, and which usually live in soft bottoms. One of the most conspicuous characteristic of the new species is its aquiferous system, which is formed by a system of superficial canals and meandering ridges which run around the entire length of the branches. The species is compared with Axinella polycapella from Gulf of Mexico, which is very close in morphology, and which it shares a high similarity in the 18S ribosomal RNA region. It was also compared with Axinella aruensis, a very different species from a morphological point of view, which is distributed throughout the northern Australia, Indonesia and Papua New Guinea as both species share a high similarity in the COI mitochondrial gene region. The new species was included in the clade named Axinella by Gazave et al. (2010) for 18S and COI, where also are included eight Axinella-species. Species in this clade are typically arborescent with a choanosomal skeleton differentiated between axial and extra-axial regions. Axinella nayaritensis n. sp. constitute the first record of an Axinella for the east Pacific coast.
A new groundwater species of Pseudoniphargus (Amphipoda: Pseudoniphargidae) fromAlgeria
Authors: DOLE-OLIVIER MARIE-JOSE , HAFID HINDA , PISCART CHRISTOPHE
Published: September 2018

Intensive sampling performed in the area of Oum El Bouaghi (Northeastern Algeria) yielded a new species of the stygobiont amphipod Pseudoniphargus, P. djemoi, in wells located in the plain of Tamlouka. The new species belongs to a group that shares the display of a uropod 3 exopod extremely elongate and upcurved in the male, whereas its peduncle is only moderately elongate. This cluster of species appears scattered across the southern Iberian Peninsula, Northern Morocco and the Canary Islands. This discovery increases the number of described species of the stygobiont amphipod genus Pseudoniphargus in north Africa to eight. A key to the species of Pseudoniphargus living in Continental Africa and Mediterranean Islands is provided.
An Aircraft-Based Study of Strong Gap Flows in Nares Strait, Greenland
Authors: Heinemann Günther
Published: September 2018

Gap flows and the stable boundary layer were studied in northwest Greenland during the aircraft-based Investigation of Katabatic Winds and Polynyas during Summer (IKAPOS) experiment in June 2010. The measurements were performed using the research aircraft POLAR 5 of Alfred Wegener Institute (AWI; Bremerhaven). Besides navigational and basic meteorological instrumentation, the aircraft was equipped with radiation and surface temperature sensors and a turbulence measurement system. In the area of Smith Sound at the southern end of the Nares Strait, a stable, but fully turbulent, boundary layer with strong winds of up to 22 m s−1 was found during conditions of synoptically induced northerly winds through the Nares Strait. Strong surface inversions were present in the lowest 100–200 m. As a consequence of channeling effects, a well-pronounced low-level jet system was documented for each of four flights. The wind maximum is located at 20–50-km distance from the exit of Smith Sound. The 3D boundary layer structure past this gap is studied in detail. The channeling process is consistent with gap flow theory. The flow through the gap and over the surrounding mountains leads to the lowering of isotropic surfaces and the acceleration of the flow. The orographically channeled flow through Smith Sound plays a key role for the formation of the North Water polynya being the largest ice-producing polynya in the Arctic.
Formative research to underpin a text messaging home safety intervention for young mothers
Authors: Mello Michael J , Gilbard Zoe , Burstein Dina , Baird Janette , Zonfrillo Mark R , Flanagan Patricia , Linakis James G , Hackman Holly , Howland Jonathan
Published: September 2018

Objective:

Unintentional injury is the leading cause of death for infants and young children in the USA, and the children of young mothers are at an even higher risk. Mobile health (mHealth) interventions have been successful in promoting behaviour change for many health conditions. This study assessed interest in mSafety, a text and video messaging mHealth intervention targeting injury prevention knowledge, behaviour and self-efficacy in young mothers.

Design:

Interviews with young mothers were conducted using a semi-structured interview guide.

Setting:

Interviews took place at a health clinic for teenage mothers and their children and at a local public charter high school which serves pregnant teenagers and young mothers.

Method:

A trained research assistant conducted semi-structured interviews with 20 young mothers (ages 15–20). Participants were asked both closed and open-ended questions to elicit opinions about their willingness to utilise mSafety.

Results:

The results of the interviews were positive. Participants were most interested in learning about the prevention of falls and poisonings, as well as safe sleep. Many emphasised that the language of the messages should be simple and that videos could be included to demonstrate methods of injury prevention. Most interviewees were willing to participate in a ‘virtual home safety visit’ in which participants text home photos to an expert to evaluate home safety practices.

Conclusion:

The concept of an mHealth intervention that would provide young mothers with the tools to prevent injuries among their children received positive feedback.
Treat a Cop Like They Are God: Exploring the Relevance and Utility of Funds of Gang Knowledge Among Latino Male Students
Authors: Huerta Adrian H. , Rios-Aguilar Cecilia
Published: September 2018

Latinos represent 20% of the more than 1 million gang-associated youth in the United States. This study explores how gang associated Latino males use their funds of gang knowledge to navigate their urban schools and communities. The findings highlight how Latino males build relationships and exchange information with each other, endure and persevere during juvenile incarceration, how youth interact with law enforcement, and how youth advance their status in gangs. Educators must learn how to anticipate and support gang-associated Latino males to understand their social worlds they bring into schools.
The effectiveness of probation supervision towards reducing reoffending: A Rapid Evidence Assessment
Authors: Smith Andrew , Heyes Kim , Fox Chris , Harrison Jordan , Kiss Zsolt , Bradbury Andrew
Published: September 2018

In response to the lack of universal agreement about ‘What Works’ in probation supervision (Trotter, 2013) we undertook a Rapid Evidence Assessment of the empirical literature. Our analysis of research into the effect of probation supervision reducing reoffending included 13 studies, all of which employed robust research designs, originating in the USA, UK, Canada and Australia, published between 2006 and 2016. We describe the papers included in our review, and the meta-analyses of their findings. Overall, we found that the likelihood of reoffending was shown to be lower for offenders who had been exposed to some type of supervision. This finding should be interpreted cautiously however, given the heterogeneity of the studies. We suggest future research and methodological considerations to develop the evidence base concerning the effectiveness of probation supervision.