bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Lead Exposure Results in Auditory Deficits and Disruption of Hair Cells in Postweaning Rats
Authors: Hu Shou-Sen , Cai Shi-Zhong , Kong Xiang-Zhen
Published: May 2019

Objective.The effects of lead exposure on cognitive function have been studied intensively over the past decade, but less attention has focused on its impact on auditory function. This study is aimed at investigating the effect of lead on the cochlea and the molecular mechanisms responsible for its actions.Methods.0.2% lead acetate was administered to rats in drinking water for 30, 60, and 90 days. Brainstem auditory evoked responses (ABR) were recorded, and morphological changes in the hair cells were observed. We also measured glutathione (GSH) and malondialdehyde (MDA) concentrations and antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities in the cochlea.Results.Lead exposure increased the ABR threshold and slightly prolonged the latencies of wave II and wave IV in rats. Abnormally shaped hair cells and loss of hair cells were found in the cochlea basilar membrane, together with degenerative changes in spiral ganglion neurons following lead exposure. The activities of some antioxidant enzymes were also reduced in association with upregulation of MDA expression. These effects may be caused by impaired catalytic function of the enzymes as a result of lead interaction.Conclusion.The antioxidant system of the cochlea in the immature rat brain is highly vulnerable to developmental lead exposure. Oxidative stress may therefore represent a possible mechanism for lead-induced auditory deficits.
A Simple Flexible and Robust Control Strategy for Wind Energy Conversion Systems Connected to a Utility Grid
Authors: Simo Fotso Armel , Kenné Godpromesse , Douanla Rostand Marc
Published: May 2019

This paper presents a simple and robust control strategy for a variable speed wind turbine conversion system using a squirrel-cage induction generator and a three-phase voltage source (AC/DC/AC) Pulse Width Modulation (PWM) converter connected to the utility grid through an LCL filter. The control strategy integrates for the generator side an adaptive radial basis function (RBF) neurosliding mode controller associated with the rotor flux oriented vector control which is used to regulate the turbine rotation speed, rotor flux, and the DC bus voltage. For the grid side, the inverter current and voltage regulation as well as the current injected into the grid are regulated by PI controllers for two modes of operation, namely, the stand-alone mode and grid connected mode. The main contribution of this article is the introduction of a new and simple control algorithm allowing automatic mode switching method based on wind speed. The proposed scheme is very efficient and can be easily implemented in practice. Simulation results illustrate the effectiveness and feasibility of the proposed algorithm.
Coupled Thermo-Hydro-Mechanical-Chemical Modeling of Permeability Evolution in a CO2-Circulated Geothermal Reservoir
Authors: Tao Jing , Wu Yu , Elsworth Derek , Li Pan , Hao Yang
Published: May 2019

The meager availability of water as a heat transfer fluid is sometimes an impediment to enhanced geothermal system (EGS) development in semi-arid regions. One potential solution is in substituting CO2 as the working fluid in EGS. However, complex thermo-hydro-mechanical-chemical (THMC) interactions may result when CO2 is injected into the geothermal reservoir. We present a novel numerical model to describe the spatial THMC interactions and to better understand the process interactions that control the evolution of permeability and the heat transfer area. The permeability and porosity evolution accommodate changes driven by thermo-hydro-mechanical compaction/dilation and mineral precipitation/dissolution. Mechanical and hydraulic effects are demonstrated to exert a small and short-term influence on permeability change, while the thermal effects are manifest in the intermediate and short-term influence. The most significant and long-term influence on permeability change is by chemical effects, where decreases in fracture permeability may be of the order of 10-5 due to calcite precipitation in fracture throats, which causes the overall permeability to reduce to 70% of the initial permeability. The initial pressure and temperature of the injected CO2 exerts an overriding influence on permeability. In particular, an increased temperature reduces the mineral precipitation in the fracture and enhances mineral dissolution within the matrix and pore but results in mechanical closure of the fractures. Optimizing injection pressure and temperature may allow the minimization of precipitation and the maximization of heat recovery.
How Have Travelers Changed Mode Choices for First/Last Mile Trips after the Introduction of Bicycle-Sharing Systems: An Empirical Study in Beijing, China
Authors: Fan Aihua , Chen Xumei , Wan Tao
Published: May 2019

In recent years, there has been rapid development in bicycle-sharing systems (BSS) in China. Moreover, such schemes are considered promising solutions to the first/last mile problem. This study investigates the mode choice behaviors of travelers for first/last mile trips before and after the introduction of bicycle-sharing systems. Travel choice models for first/last mile trips are determined using a multinomial logit model. It also analyzes the differences in choice behavior between the young and other age groups. The findings show that shared bicycles become the preferred mode, while travelers preferred walking before bicycle-sharing systems were implemented. Gender, bicycle availability, and travel frequency were the most significant factors before the implementation of bicycle-sharing systems. However, after implementation, access distance dramatically affects mode choices for first/last mile trips. When shared bicycles are available, the mode choices of middle-aged group depend mainly on gender and access distance. All factors are not significant for the young and aged groups. More than 80% of public transport travelers take walking and shared bicycles as feeder modes. The proposed models and findings contribute to a better understanding of travelers’ choice behaviors and to the development of solutions for the first/last mile problem.
Knee Joint Biomechanical Gait Data Classification for Knee Pathology Assessment: A Literature Review
Authors: Abid Mariem , Mezghani Neila , Mitiche Amar
Published: May 2019

Background. The purpose of this study is to review the current literature on knee joint biomechanical gait data analysis for knee pathology classification. The review is prefaced by a presentation of the prerequisite knee joint biomechanics background and a description of biomechanical gait pattern recognition as a diagnostic tool. It is postfaced by discussions that highlight the current research findings and future directions. Methods. The review is based on a literature search in PubMed, IEEE Xplore, Science Direct, and Google Scholar on April 2019. Inclusion criteria admitted articles, written in either English or French, on knee joint biomechanical gait data classification in general. We recorded the relevant information pertaining to the investigated knee joint pathologies, the participants’ attributes, data acquisition, feature extraction, and selection used to represent the data, as well as the classification algorithms and validation of the results. Results. Thirty-one studies met the inclusion criteria for review. Conclusions. The review reveals that the importance of medical applications of knee joint biomechanical gait data classification and recent progress in data acquisition technology are fostering intense interest in the subject and giving a strong impetus to research. The review also reveals that biomechanical data during locomotion carry essential information on knee joint conditions to infer an early diagnosis. This survey paper can serve as a useful informative reference for research on the subject.
Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression
Authors: Xia Liang , Liu Jingjing , Sun Yuanyuan , Shi Haibo , Yang Guang , Feng Yanmei , Yin Shankai
Published: May 2019

In this study, we investigated the role of MAP kinase phosphatase-1 (MKP-1) and rosiglitazone (RSG) in glucocorticoid resistance and glucocorticoid sensitivity, respectively, using a guinea pig model of lipopolysaccharide- (LPS-) induced sudden sensorineural hearing loss (SSHL). The pigs were divided into control, LPS, LPS+dexamethasone (DEX), LPS+RSG, and LPS+DEX+RSG groups. Their hearing was screened by auditory brainstem response measurement. Immunofluorescence staining was used to identify the location of MKP-1 in the inner ear. The expression levels of MKP-1 and the related proteins in the inner ear were detected using western blotting. The morphological changes in the cochlea were observed via hematoxylin-eosin staining. Severe hearing loss was observed in the LPS group, as opposed to the protection from hearing loss observed in the LPS+DEX+RSG group. A positive correlation was observed between MKP-1 expression levels and protection from hearing loss. RSG and DEX synergistically influenced inner ear inflammation. In conclusion, resistance of LPS-induced SSHL guinea pig models to glucocorticoids may result from impaired MKP-1 function in inner ear tissues, induced by glucocorticoids, impairing the inhibition of inflammation. Our findings present novel targets to develop potential therapeutics to treat inflammatory diseases of the inner ear.
Molecular Residual Disease and Adjuvant Trial Design in Solid Tumors
Authors: Coakley Maria , Garcia-Murillas Isaac , Turner Nicholas C.
Published: May 2019

Advances in diagnosis and treatment have resulted in a high rate of survival for many patients with early-stage cancers. However, identifying who is at ongoing risk of relapse remains of high priority to direct subsequent adjuvant therapy. Multiple recent retrospective studies have shown that detection of tumor-derived materials in blood, in particular with circulating tumor DNA (ctDNA) analysis, can identify patients with residual disease before clinical or radiological evidence of metastatic disease, anticipating relapse with relatively high sensitivity and high specificity. We discuss how these emerging technologies are defining new subgroups of patients with “Molecular Residual Disease” and “Molecular Relapse.” We outline how novel clinical trials in the adjuvant setting designed for these new subgroups of patients may improve selection for adjuvant therapies, and provide new surrogate endpoints that may allow for early registration of adjuvant therapies and novel clinical trial designs in the adjuvant setting. We discuss the current limitations of these techniques and the routes to clinical implementation.
Activation of PPARγ in Myeloid Cells Promotes Progression of Epithelial Lung Tumors through TGFβ1
Authors: Sippel Trisha R. , Johnson Amber M. , Li Howard Y. , Hanson Dwight , Nguyen Teresa T. , Bullock Bonnie L. , Poczobutt Joanna M. , Kwak Jeff W. , Kleczko Emily K. , Weiser-Evans Mary C. , Nemenoff Raphael A.
Published: May 2019

Lung cancer is a heterogeneous disease in which patient-specific treatments are desirable and the development of targeted therapies has been effective. Although mutations in KRAS are frequent in lung adenocarcinoma, there are currently no targeted agents against KRAS. Using a mouse lung adenocarcinoma cell line with a Kras mutation (CMT167), we previously showed that PPARγ activation in lung cancer cells inhibits cell growth in vitro yet promotes tumor progression when activated in myeloid cells of the tumor microenvironment. Here, we report that PPARγ activation in myeloid cells promotes the production of TGFβ1, which, in turn, acts on CMT167 cancer cells to increase migration and induce an epithelial–mesenchymal transition (EMT). Targeting TGFβ1 signaling in CMT167 cells prevented their growth and metastasis in vivo. Similarly, another mouse lung adenocarcinoma cell line with a Kras mutation, LLC, induced TGFβ1 in myeloid cells through PPARγ activation. However, LLC cells are more mesenchymal and did not undergo EMT in response to TGFβ1, nor did LLC require TGFβ1 signaling for metastasis in vivo. Converting CMT167 cells to a mesenchymal phenotype through overexpression of ZEB1 made them unresponsive to TGFβ1 receptor inhibition. The ability of TGFβ1 to induce EMT in lung tumors may represent a critical process in cancer progression. We propose that TGFβ receptor inhibition could provide an additional treatment option for KRAS-mutant epithelial lung tumors.

Implications: This study suggests that TGFβ receptor inhibitors may be an effective therapy in a subset of KRAS-mutant patients with non–small cell lung cancer, which show an epithelial phenotype.
Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer
Authors: Dougherty Urszula , Mustafi Reba , Haider Haider I. , Khalil Abdurahman , Souris Jeffrey S. , Joseph Loren , Hart John , Konda Vani J. , Zhang Wei , Pekow Joel , Li Yan Chun , Bissonnette Marc
Published: May 2019

Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker. Control Apc+/LoxP mice and tumor-forming Apc+/LoxP Cdx2P-Cre mice were randomized to unsupplemented Western diet (UN), or diets supplemented with VD, L, or VD+L, the latter to assess additive or synergistic effects. At 6 months, mice were killed. Plasma Ca2+, 25(OH)D3, 1α, 25(OH)2D3, renin, and angiotensin II (Ang II) were quantified. Colonic transcripts were assessed by qPCR and proteins by immunostaining and blotting. Cancer incidence and tumor burden were significantly lower in Cre+ VD and Cre+ L, but not in the Cre+ VD+L group. In Apc+/LoxP mice, VD increased plasma 1,25(OH)2D3 and colonic VDR. In Apc+/LoxP-Cdx2P-Cre mice, plasma renin and Ang II, and colonic tumor AT1, AT2, and Cyp27B1 were increased and VDR downregulated. L increased, whereas VD decreased plasma renin and Ang II in Cre+ mice. VD or L inhibited tumor development, while exerting differential effects on plasma VD metabolites and RAS components. We speculate that AT1 is critical for tumor development, whereas RAS suppression plays a key role in VD chemoprevention. When combined with L, VD no longer increases active VD and colonic VDR in Cre- mice nor suppresses renin and Ang II in Cre+ mice, likely contributing to lack of chemopreventive efficacy of the combination.
Hypoxia-Induced VISTA Promotes the Suppressive Function of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Authors: Deng Jie , Li Jiannan , Sarde Aurelien , Lines J. Louise , Lee Yu-Chi , Qian David C. , Pechenick Dov A. , Manivanh Richard , Le Mercier Isabelle , Lowrey Christopher H. , Varn Frederick S. , Cheng Chao , Leib David A. , Noelle Randolph J. , Mabaera Rodwell
Published: May 2019

Tumor hypoxia is a negative prognostic factor that is implicated in oncogenic signal activation, immune escape, and resistance to treatment. Identifying the mechanistic role of hypoxia in immune escape and resistance to immune-checkpoint inhibitors may aid the identification of therapeutic targets. We and others have shown that V-domain Ig suppressor of T-cell activation (VISTA), a negative checkpoint regulator in the B7 family, is highly expressed in the tumor microenvironment in tumor models and primary human cancers. In this study, we show that VISTA and HIF1α activity are correlated in a cohort of colorectal cancer patients. High VISTA expression was associated with worse overall survival. We used the CT26 colon cancer model to investigate the regulation of VISTA by hypoxia. Compared with less hypoxic tumor regions or draining lymph nodes, regions of profound hypoxia in the tumor microenvironment were associated with increased VISTA expression on tumor-infiltrating myeloid-derived suppressor cells (MDSC). Using chromatin immunoprecipitation and genetic silencing, we show that hypoxia-inducible factor (HIF)-1α binding to a conserved hypoxia response element in the VISTA promoter upregulated VISTA on myeloid cells. Further, antibody targeting or genetic ablation of VISTA under hypoxia relieved MDSC-mediated T-cell suppression, revealing VISTA as a mediator of MDSC function. Collectively, these data suggest that targeting VISTA may mitigate the deleterious effects of hypoxia on antitumor immunity.
Speech and Language Therapy Services for Multilingual Children with Migration Background: A Cross-Sectional Survey in Germany
Authors: Scharff Rethfeldt Wiebke
Published: May 2019

Speech, language, and communication needs are particularly common among multilingual and migrant children. More than every third child in Germany has a migrant background. In the city of Bremen, this figure is even higher, including refugee children. The availability of comprehensive data on the provision and uptake of speech and language therapy (SLT) services is still inadequate, especially for multilingual children. However, health-monitoring programs report that migrants differ in many health-related areas from the majority population, mainly in barriers in health care. This study examines the current provision of SLT services for multilingual children following a medical prescription for the specific case of suspected language disorder. Information was obtained from speech-language pathologists (SLPs) representing 28 practices in different districts across one of the moderately largest cities affected by sociospatial polarization. The SLT practices were clustered according to the proportion of minor migrants and minor welfare recipients in the district. The survey included the number and proportion of multilingual children on the SLT caseloads, as well as the age of children by time of referral, physician and SLP diagnoses, application and type of assessment materials, intervention goals, and sociodemographic data of practicing SLPs. Questionnaire responses were analyzed using descriptive statistics and an explanatory interpretive approach. Findings suggest that multilingual children experience later referral compared to monolingual German-speaking children, with approximately half of the multilingual children demonstrating a developmental language disorder (DLD). The SLP’s level of experience determines the accuracy of differential diagnosis between communication disorders and typical linguistic variations. Consequently, participation in continuing education focusing on service provision of the multilingual and multicultural clientele is essential. This study highlights the obstacles and the needs for increased multiprofessional awareness and an enhanced professional knowledge to provide effective and swift diagnosis earlier to allow multilingual children with a DLD to access relevant services on equal terms with native resident children.
The Course of von Willebrand Factor and Factor VIII Activity in Patients with von Willebrand Disease during Pregnancy
Authors: Delbrück Christiane , Miesbach Wolfgang
Published: May 2019

Introduction: Women with von Willebrand disease (VWD) are at a higher risk of bleeding, which might affect the health of mother and child during pregnancy and the intra- and postpartum periods. This retrospective cohort study evaluates changes in the coagulation parameters von Willebrand factor antigen (VWF:Ag), von Willebrand ristocetin cofactor (VWF:RCo), and Factor VIII activity (FVIII:C) during pregnancy in patients with VWD. In total, 44 pregnancies of 38 patients were assessed (VWD type 1 n = 32, type 2A n = 3, type 2B n = 1, type 2 subtype unidentified n = 2). The patients’ median age at childbirth was 32 years (range 22–40). Results: A significant increase in coagulation parameters was found in patients with VWD type 1 (VWF:Ag, VWF:RCo, and FVIII:C p = 0.000). In the third trimester, VWF:Ag and FVIII:C normalized in all patients with VWD type 1; in 3 patients VWF:RCo remained below the normal range. Patients with VWD type 2 showed a significant increase of VWF:Ag (p = 0.003) and FVIII:C (p = 0.011), and a non-significant increase of VWF:RCo (p = 0.097). In 4 of 9 pregnancies of patients with VWD type 2, all surveyed coagulation parameters normalized until the third trimester. Conclusion: For the majority of the observed patients, the von Willebrand parameters increased during pregnancy.
Exogenous Ketone Bodies as Promising Neuroprotective Agents for Developmental Brain Injury
Authors: Wood Thomas R. , Stubbs Brianna J. , Juul Sandra E.
Published: May 2019

Ketone bodies are a promising area of neuroprotection research that may be ideally suited to the injured newborn. During normal development, the human infant is in significant ketosis for at least the first week of life. Ketone uptake and metabolism is upregulated in the both the fetus and neonate, with ketone bodies providing at least 10% of cerebral metabolic energy requirements, as well as being the preferred precursors for the synthesis of fatty acids and cholesterol. At the same time, ketone bodies have been shown to have multiple neuroprotective effects, including being anticonvulsant, decreasing oxidative stress and inflammation, and epigenetically upregulating the production of neurotrophic factors. While ketogenic diets and exogenous ketosis are largely being investigated in the setting of adult brain injury, the adaptation of the neonate to ketosis suggests that developmental brain injury may be the area most suited to the use of ketones for neuroprotection. Here, we describe the mechanisms by which ketone bodies exert their neuroprotective effects, and how these may translate to benefits within each of the phases of neonatal asphyxial brain injury.
Acquired Enamel Pellicle Modification with Casein and Mucin in Different Concentrations and its Impact on Initial Dental Erosion
Authors: Sieber Kevin R. , Schmidt Christoph , Baumann Tommy , Lussi Adrian , Carvalho Thiago S.
Published: May 2019

Casein and mucin have been shown to improve the erosion-protective properties of the pellicle when applied in combination. The aim of this in vitro study was to optimize the concentrations of these 2 proteins to achieve a maximum protective effect. For the 2 parts of this study, we prepared a total of 195 human enamel specimens and randomly assigned them to 13 groups, corresponding to 11 different casein-mucin concentration-combinations tested and 2 negative control groups (humid chamber). They underwent 5 cycles, consisting of pellicle formation from human whole saliva (2 h, 30°C), modification of the pellicle with casein and mucin in different concentrations (immersion in protein solutions for 2 h, 30°C), and erosion for 1 min in citric acid (0.65%, pH 3.5, 30°C). Surface microhardness (SMH), surface reflection intensity (SRI), and in the first part also calcium release were monitored during the cycling process, and analyzed with Kruskal-Wallis and post hoc Dunn’s tests. The results suggest that the best concentrations to achieve the highest erosion-protective effect are 3.0% casein and 0.81% mucin, which lead to a significant protection as measured by SMH as well as SRI compared to the unmodified pellicle. For the calcium release, no significant differences were found. This concentration combination corresponds to a general raise of the protein concentrations and a change in the molar ratio of the proteins as compared to earlier studies. Casein and mucin could now be incorporated at the determined concentration as natural ingredients in oral care products designed to protect against erosion.
North American Expert Review of Rotational Atherectomy
Authors: Sharma Samin K. , Tomey Matthew I. , Teirstein Paul S. , Kini Annapoorna S. , Reitman Arthur B. , Lee Arthur C. , Généreux Philippe , Chambers Jeffrey W. , Grines Cindy L. , Himmelstein Stevan I. , Thompson Craig A. , Meredith Ian T. , Bhave Aparna , Moses Jeffrey W.
Published: May 2019

Rotational atherectomy (RA) is an established tool in interventional cardiology for treatment of calcified coronary lesions. Over 3 decades of clinical experience and research, techniques have matured and outcomes have improved. Heterogeneity exists, however, in RA utilization and technique. We assembled a group of experienced RA operators and device experts to summarize and critique key elements of contemporary RA technique, to identify areas of consensus and controversy, and to offer recommendations for optimal performance for the practicing interventional cardiologist. Evolution in RA strategy toward a focus on lesion modification to facilitate balloon angioplasty and stenting has underpinned major advances in procedural safety, including opportunity to use smaller caliber equipment and radial access. Optimal technique and improved safety have permitted exploratory use of RA for different lesion types and reevaluation of procedural requirements, including flush solution composition and transvenous pacing. Preparedness to manage complications remains paramount and recommendations for operators and institutions are outlined.
Use of Medicare Claims to Identify Adverse Clinical Outcomes After Mitral Valve Repair
Authors: Lowenstern Angela , Lippmann Steven J. , Brennan J. Matthew , Wang Tracy Y. , Curtis Lesley H. , Feldman Ted , Glower Donald D. , Hammill Bradley G. , Vemulapalli Sreekanth
Published: May 2019

Background:

Clinical event committees are commonly employed for event validation in clinical studies, but little is known about the comparative performance of administrative claims data versus clinician-triggered event adjudication for ascertainment of adverse events in structural heart disease studies.

Methods and Results:

Medicare claims were linked to 418 patients >65 years of age who underwent transcatheter mitral valve repair (MitraClip) for severe mitral regurgitation from 2007 to 2013 as part of the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study II) High-Risk Registry or the REALISM (Real World Expanded Multicenter Study of the MitraClip System) Continued-Access Registry. Each registry adjudicated mortality, heart failure hospitalization, renal failure, ventilation, and bleeding/transfusion within 1 year. Concordance of claims-based outcomes with events was assessed in 3 ways: 1-year occurrence, cumulative incidence, and synchrony of first events. For event occurrence, positive predictive value (PPV) of claims versus adjudication was the highest for mortality (PPV=97%) and heart failure hospitalization (PPV=69%) but lower for bleeding (PPV=40%) and renal failure (PPV=19%). Whereas claims-based cumulative incidence for mortality, heart failure hospitalization, and renal failure were consistent with clinician-triggered adjudication, incidence curves for bleeding events and ventilation diverged, with claims identifying a greater number of events. When events were detected by both methods, however, over 75% of event dates matched exactly. Mitral valve reinterventions were identified through claims with perfect sensitivity and specificity relative to physician adjudication.

Conclusions:

Ascertainment of mortality, heart failure hospitalization, and renal failure was highly concordant between physician adjudication and administrative claims. Further work is necessary to determine the role of administrative claims in event ascertainment in both prospective and retrospective studies of structural heart disease.
Circulating Selenium Concentration Is Inversely Associated With the Prevalence of Stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey
Authors: Hu Xue Feng , Stranges Saverio , Chan Laurie H. M.
Published: May 2019

Background

Observational studies have suggested that selenium (Se) may have beneficial effects against certain cardiovascular outcomes, with a possible U‐shaped association. We assessed the hypothesis that blood Se concentration might be inversely associated with the prevalence of stroke and the relationship would be nonlinear.

Methods and Results

Data collected from adult participants (aged ≥20 years) in the Canadian Health Measures Survey (
CHMS
2007–2011, n=7065) and the
US
National Health and Nutrition Examination Survey (
NHANES
2011–2012, n=5030) were analyzed. A total of 82 (1.16%) and 202 (4.02%) stroke cases were identified in
CHMS
and
NHANES
. Respondents with stroke had lower Se levels than those without stroke, with a mean difference of 16 μg/L and 12 μg/L for
CHMS
and
NHANES
, respectively. Respondents with high blood Se concentration (tertile 3) had a lower prevalence of stroke compared with those with low Se concentration (tertile 1). The adjusted odds ratios were 0.38 (95%
CI
: 0.15, 0.92) and 0.57 (95%
CI
: 0.31, 1.03) for
CHMS
and
NHANES
, respectively. A continuous decreasing trend of stroke with whole blood selenium was observed in
CHMS
, whereas the curve plateaued starting at 190 μg/L for
NHANES
, based on the cubic restricted spline regression. Sensitivity analysis using the serum and urinary Se concentrations demonstrates that our results were consistent across different selenium biomarkers.

Conclusions

We observed inverse cross‐sectional associations between whole blood Se and the prevalence of stroke in representative samples of the Canadian and the
US
population.
Overlap in the Genetic Architecture of Stroke Risk, Early Neurological Changes, and Cardiovascular Risk Factors
Authors: Ibanez Laura , Heitsch Laura , Dube Umber , Farias Fabiana H.G. , Budde John , Bergmann Kristy , Davenport Rich , Bradley Joseph , Carrera Caty , Kinnunen Janne , Sallinen Hanne , Strbian Daniel , Slowik Agnieszka , Fernandez-Cadenas Israel , Montaner Joan , Lee Jin-Moo , Cruchaga Carlos ,   on behalf of the International Stroke Genetics Consortium and the MEGASTROKE Consortium*
Published: May 2019

Background and Purpose—

The genetic relationships between stroke risk, stroke severity, and early neurological changes are complex and not completely understood. Genetic studies have identified 32 all stroke risk loci. Polygenic risk scores can be used to compare the genetic architecture of related traits. In this study, we compare the genetic architecture of stroke risk, stroke severity, and early neurological changes with that of 2 stroke risk factors: type 2 diabetes mellitus (T2DM) and hypertension.

Methods—

We assessed the degree of overlap in the genetic architecture of stroke risk, T2DM, hypertension, and 2 acute stroke phenotypes based on the National Institutes of Health Stroke Scale (NIHSS), which ranges from 0 for no stroke symptoms to 21 to 42 for a severe stroke: baseline (within 6 hours after onset) and change in NIHSS (ΔNIHSS=NIHSS at baseline−NIHSS at 24 hours). This was done by (1) single-nucleotide polymorphism by single-nucleotide polymorphism comparison, (2) weighted polygenic risk scores with sentinel variants, and (3) whole-genome polygenic risk scores using multiple
P
thresholds.

Results—

We found evidence of genetic architecture overlap between stroke risk and T2DM (
P
=2.53×10
−
169
), hypertension (
P
=3.93×10
−
04
), and baseline NIHSS (
P
=0.03). However, there was no evidence of overlap between ΔNIHSS and stroke risk, T2DM, or hypertension.

Conclusions—

The genetic architecture of stroke risk is correlated with that of T2DM, hypertension, and initial stroke severity (NIHSS within 6 hours of stroke onset). However, the genetic architecture of early neurological change after stroke (ΔNIHSS) is not correlated with that of ischemic stroke risk, T2DM, or hypertension. Thus, stroke risk and early neurological change after stroke have distinct genetic architectures.
Location of Neutrophils in Different Compartments of the Damaged Mouse Brain After Severe Ischemia/Reperfusion
Authors: Otxoa-de-Amezaga Amaia , Gallizioli Mattia , Pedragosa Jordi , Justicia Carles , Miró-Mur Francesc , Salas-Perdomo Angelica , Díaz-Marugan Laura , Gunzer Matthias , Planas Anna M.
Published: May 2019

Background and Purpose—

Ischemia attracts neutrophils to the injured brain. However, neutrophil location and access to the damaged brain tissue is not yet entirely understood. We aimed to investigate neutrophil location in a mouse model of cerebral ischemia/reperfusion.

Methods—

Adult male C57BL/6 mice (n=52) received 45-minute intraluminal middle cerebral artery occlusion followed by 14, 24, 48, or 96 hours of reperfusion. Sham-operated mice (n=9) were subjected to the entire surgical procedure. We used wild-type mice and Catchup
IVM
mice expressing a red fluorescent protein in neutrophils. In addition, fluorescent neutrophils obtained from reporter DsRed (discosoma red fluorescent protein) mice were transferred intravenously to wild-type mice after ischemia. Mice received transcardial paraformaldehyde perfusion, the brain was cryoprotected, frozen, and cryostat sections were studied by immunofluorescence and confocal microscopy.

Results—

Ischemia induced a time-dependent increase in brain neutrophil numbers versus sham operation. We detected neutrophils in the leptomeninges, ventricles, capillary lumen, perivascular spaces, and parenchyma within the infarcted core. Most ischemic mice showed neutrophils in the leptomeninges and perivascular spaces, whereas the presence and number of neutrophils in the parenchyma was variable among ischemic mice. During the first 24 hours, only a few mice showed parenchymal neutrophils, but the frequency of mice showing neutrophils in the parenchyma and neutrophil numbers increased at 48 and 96 hours. We also detected signs of basement membrane disruption and hints of occasional neutrophil degranulation and formation of neutrophil extracellular traps.

Conclusions—

After ischemia/reperfusion, neutrophils accumulate in the leptomeninges and perivascular spaces, and eventually can reach the infarcted brain parenchyma.
Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation
Authors: Sur Nicole B. , Wang Kefeng , Di Tullio Marco R. , Gutierrez Carolina M. , Dong Chuanhui , Koch Sebastian , Gardener Hannah , García-Rivera Enid J. , Zevallos Juan Carlos , Burgin W. Scott , Rose David Z. , Goldberger Jeffrey J. , Romano Jose G. , Sacco Ralph L. , Rundek Tatjana
Published: May 2019

Background and Purpose—

Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications.

Methods—

The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors.

Results—

Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%–40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07–1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86–0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84–0.99). There was no sex difference in use of DOACs.

Conclusions—

Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03627806.
SCENT Trial
Authors: Meyers Philip M. , Coon Alexander L. , Kan Peter T. , Wakhloo Ajay K. , Hanel Ricardo A.
Published: May 2019

Background and Purpose—

To evaluate the safety and effectiveness of the Surpass Flow Diverter (Surpass; Stryker Neurovascular, Fremont, CA) in the treatment of large or giant wide-neck intracranial aneurysms at one year, we hypothesize that treatment with Surpass meets or improves on historical safety and efficacy end points.

Methods—

SCENT trial (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms) is a multicenter, prospective, single-arm, nonrandomized, interventional trial of the Surpass Flow Diverter for uncoilable or previously treated but failed aneurysms of the intracranial internal carotid artery extending from the petrous segment to the carotid terminus at its bifurcation into anterior and middle cerebral arteries. For enrollment in SCENT, target aneurysms had to be wide-neck (≥4 mm) and large or giant size (≥10 mm). Study results are compared with performance goals derived from a thorough review of the medical literature. The primary effectiveness end point included 3 components: complete aneurysm occlusion, absence of significant parent artery stenosis (≥50%), and no retreatment at 12 months. The primary safety end point was major ipsilateral stroke (increase in National Institutes of Health Stroke Scale score of ≥4) or neurological death within 12 months.

Results—

At 26 medical centers, 180 patients with 180 target aneurysms were enrolled in the modified intention-to-treat cohort. Per angiographic core lab assessment, there were 15 (8.3%) fusiform, 164 (91.1%) saccular aneurysms, and 1 (0.6%) blister aneurysm. Mean aneurysm size was 12.0 mm. Thirteen (7.4%) aneurysms were giant (≥25 mm). Fifty-eight (32.2%) aneurysms were located in the supraclinoid and distal (including posterior communicating artery) segments of the internal carotid artery. Mean procedure duration was 53.6 minutes. The device was successfully implanted in 97.8% of patients with a mean of 1.1 devices per patient. SCENT met both primary safety and effectiveness end points: 12-month primary effectiveness rate was 62.8% [(113/180); 95% CI, 55.3–69.9] and 12-month major ipsilateral stroke or neurological death rate was 8.3% [(15/180); 95% CI, 4.7–13.4].

Conclusions—

Surpass provides safe and effective flow diversion of large or giant, wide-neck, intracranial internal carotid artery aneurysms.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01716117.
Thrombectomy Outcomes of Intracranial Atherosclerosis-Related Occlusions
Authors: Tsang Anderson Chun On , Orru Emanuele , Klostranec Jesse M. , Yang I-Hsiao , Lau Kui Kai , Tsang Frederick Chun Pong , Lui Wai Man , Pereira Vitor Mendes , Krings Timo
Published: May 2019

Background and Purpose—

Intracranial atherosclerosis (ICAS) is an important cause of large vessel occlusion and poses unique challenges for emergent endovascular thrombectomy. The risk factor profile and therapeutic outcomes of patients with ICAS-related occlusions (ICAS-O) are unclear. We performed a systematic review and meta-analysis of studies reporting the clinical features and thrombectomy outcomes of large vessel occlusion stroke secondary to underlying ICAS (ICAS-O) versus those of other causes (non–ICAS-O).

Methods—

A literature search on thrombectomy for ICAS-O was performed. Random-effect meta-analysis was used to analyze the prevalence of stroke risk factors and outcomes of thrombectomy between ICAS-O and non–ICAS-O groups.

Results—

A total of 1967 patients (496 ICAS-O and 1471 non–ICAS-O) were included. The ICAS-O group had significantly higher prevalence of hypertension (odds ratio [OR] 1.46; 95% CI, 1.10–1.93), diabetes mellitus (OR, 1.68; 95% CI, 1.29–2.20), dyslipidemia (OR, 1.94; 95% CI, 1.04–3.62), smoking history (OR, 2.11; 95% CI, 1.40–3.17) but less atrial fibrillation (OR, 0.20; 95% CI, 0.13–0.31) than the non–ICAS-O group. About thrombectomy outcomes, ICAS-O had higher intraprocedural reocclusion rate (OR, 23.7; 95% CI, 6.96–80.7), need for rescue balloon angioplasty (OR, 9.49; 95% CI, 4.11–21.9), rescue intracranial stenting (OR, 14.9; 95% CI, 7.64–29.2), and longer puncture-to-reperfusion time (80.8 versus 55.5 minutes, mean difference 21.3; 95% CI, 11.3–31.3). There was no statistical difference in the rate of final recanalization (modified Thrombolysis in Cerebral Infarction score of 2b/3; OR, 0.67; 95% CI, 0.36–1.27), symptomatic intracerebral hemorrhage (OR, 0.79; 95% CI, 0.50–1.24), good functional outcome (modified Rankin Scale score of 0–2; OR, 1.16; 95% CI, 0.85–1.58), and mortality (OR, 0.94; 95% CI, 0.64–1.39) between ICAS-O and non–ICAS-O.

Conclusions—

Patients with ICAS-O display a unique risk factor profile and technical challenges for endovascular reperfusion therapy. Intraprocedural reocclusion occurs in one-third of patients with ICAS-O. Intraarterial glycoprotein IIb/IIIa inhibitors infusion, balloon angioplasty, and intracranial stenting may be viable rescue treatment to achieve revascularization, resulting in comparable outcomes to non–ICAS-O.
Temporal Trends in Ischemic Stroke Incidence in Younger Adults in the Framingham Study
Authors: Aparicio Hugo J. , Himali Jayandra J. , Satizabal Claudia L. , Pase Matthew P. , Romero Jose R. , Kase Carlos S. , Beiser Alexa S. , Seshadri Sudha
Published: May 2019

Background and Purpose—

Stroke at midlife has a disproportionately large impact on disability-adjusted life-years lost. Ischemic stroke incidence may be increasing at this age. We investigated long-term trends in ischemic stroke incidence and changes in stroke risk factors in a community sample stratified by stroke onset at middle and older age.

Methods—

In the Framingham Study, surveillance for incident stroke is ongoing since 1948. We examined age-adjusted and sex-adjusted 10-year incidence of ischemic stroke using Cox models in persons aged 35 to 54 and ≥55 years at start of follow-up. Tests for linear trend were performed over 4 epochs, controlling for the distance in time between intervals. Further, we calculated the mean 10-year risk of stroke at each epoch and for both age groups, based on vascular risk factors from the Framingham Stroke Risk Profile.

Results—

There were 153, 197, 176, and 165 incident ischemic strokes within each epoch beginning in 1962 (n=3966), 1971 (n=5779), 1987 (n=5133), and 1998 (n=6964). Most ischemic strokes at midlife (n=71) were because of atherosclerotic brain infarction (n=50) or cardioembolism (n=19). Using the risk in the 1962 epoch as the reference, the risk of ischemic stroke at midlife did not significantly decline (hazard ratio, 0.87; 95% CI, 0.74–1.02;
P
trend =0.09). Incidence of ischemic stroke declined in the older group (hazard ratio, 0.82; 95% CI, 0.77–0.88;
P
trend <0.001). Between epochs 1 and 4, the average 10-year risk of stroke, as estimated by the Framingham Stroke Risk Profile, declined by 0.7% at midlife and 1.1% at older age.

Conclusions—

Long-term rates of ischemic stroke declined in our community sample; the decline was greater in older as compared with younger adults. Early prevention, focused on modification of cardiovascular risk factors, is important to see sustained declines in stroke incidence and mortality at midlife.
Claimed and Unclaimed Experience: Problematic Readings of Trauma in the Hebrew Bible
Authors: Janzen David
Published: May 2019

The understanding of trauma in sociology as the group’s creation of meaning for horrific events has been highly influential in the study of the Hebrew Bible. This sociological approach is very different than that of literary criticism, where trauma is understood through the lens of psychoanalytical analysis as that which has not been fully experienced by victims and is not truly known by them, as “unclaimed experience,” in other words. The sociological understanding of trauma has helped scholars understand potential social benefits of biblical texts, but scholarship often fails to clearly distinguish this approach from that of psychoanalysis and literary criticism, and this has led to problematic claims that texts which create meaning for traumatic events will prove to be therapeutic for individual trauma sufferers. The use of texts to create meaning and explanation actually forces trauma victims to repress the speech about their trauma that they need to engage in therapy.
Vital (Johannine) Signs: ‘Crip-tic’ Enactments of a Man at the Pool (John 5:1-18)
Authors: Lawrence* Louise J.
Published: May 2019

John 5:1-18 is here interpreted ‘crip-tically’ (through a crip hermeneutic) which seeks to pay due attention to the man at the pool and his ‘enactments’. In order to subvert notions of what Alison Kafer has termed ‘curative time’, here this sign is seen to afford something other than a normalisation or physical healing of a body. Inspiration is drawn from two recent disability arts exhibits – Liz Crow’s Bedding Out (2012-2013) and Noëmi Lakmaier’s One Morning in May (2012) – and their respective illustrations of crip time and movement to highlight how the man in John 5:1-18 too has the potential to subversively refigure ‘normative’ understandings of time, space and embodiment within the Gospel.
Is Freedom an Existential Category in Ancient Discourse?
Authors: Livesey Nina E.
Published: May 2019

In much of the Christian exegetical tradition, freedom, ἐλευθερία, is considered an existential state. Hans Dieter Betz, for instance, assessed freedom as the “central theological concept which sums up the Christian’s situation before God as well as in this world” (1979: 255). Yet in his 2001 monograph, Constructing Autocracy, the classicist Matthew Roller explains that ancient authors only employed the terms libertas (“freedom”) and its complementary term servitus (“slavery”) together as metaphors to characterize another situation. Unless they were defining what it meant to be a free person or a slave (e.g., Dio Chrysostom, Or. 14, 15), ancient authors did not employ the terms “freedom” or “slavery” to designate a political or religious state of being. When employed paradigmatically, as commentary on another situation, the terms “freedom” and “slavery” carried important social and ethical implications. This article applies Roller’s insights to Paul’s use of freedom in Galatians.
Where Public Theology and Public Administration Meet
Authors: van Putten Robert , Overeem Patrick , van Steden Ronald
Published: May 2019

Since 9/11 Jürgen Habermas has paid considerable attention to religion in the public sphere. He has described contemporary Western societies as ‘post-secular’, arguing that believers and non-believers should show a mutually cooperative attitude and engage in complementary learning processes. Although public theologians have urged for policies that would encourage such collaboration, public administration scholars and practitioners seem to have completely neglected this call. In this article we inquire into the possibility of a ‘post-secular public administration’, which grants a more significant place to beneficial forms of religion in modern societies. By presenting a case study on Street Pastors in the British night-time economy we offer an example of both a post-secular religious contribution to the public sphere, as envisaged by Habermas, and a piece of post-secular empirical social science research. Finally, we critically assess Habermas’ post-secular turn within the context of a cross-narrative between public theology and public administration.