bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Senescence-Related Differentiation Potentials and Gene Expression Profiles in Human Dental Pulp Stem Cells
Authors: Yi Qiao , Liu Ousheng , Yan Fei , Lin Xiao , Diao Shu , Wang Liping , Jin Luyuan , Wang Songlin , Lu Yanqin , Fan Zhipeng
Published: September 2016

Introduction: Dental pulp stem cell (DPSC)-mediated dental pulp regeneration is considered a promising method for the treatment of deep caries with pulpitis. However, mesenchymal stem cell (MSC) senescence is an adverse factor from the perspective of cell-based therapies. In this study, we investigated the characteristics and expression profiles of DPSCs from young and old donors. Methods: DPSCs from young and old donors were cultured in differentiation medium, and their differentiation potentials were assessed. Long noncoding RNA (LncRNA) microarray assays and a bioinformatic analysis were performed to investigate differences in LncRNA and mRNA expression profiles between DPSCs from young and old donors. Results: We found that DPSCs from young donors exhibited more powerful proliferation ability and greater osteogenic and adipogenic differentiation potentials than DPSCs from old donors. In DPSCs from young donors, numerous LncRNAs were significantly up- (n = 389) or down-regulated (n = 172) compared to DPSCs from old donors. Furthermore, 304 mRNAs were differentially expressed, including 247 up-regulated genes and 57 down-regulated genes in DPSCs from young donors. The bioinformatic analysis identified that several pathways may be associated with DPSC characteristics, such as those involved in the cell cycle and RNA transport, and revealed nuclear transcription factor Y subunit β, general transcription factor IIB, and nuclear receptor subfamily 3 group C member 1 as core regulatory factors and FR249114, FR299091, and ENST00000450004 as core LncRNAs. Conclusions: Our results indicated that senescence impaired the proliferation and differentiation potentials of DPSCs and that donor age is an important factor that affects their use for tooth regeneration. We also provide insight into the mechanisms responsible for senescence in DPSCs.
Evaluation of the Narrow Anterior Chamber Angle by Anterior Segment Optical Coherence Tomography
Authors: Lan Jie , Sun Dapeng , Alabdulrasool Khatoon , Ebrahim Yusuf Hassan , Zhang Lu
Published: September 2016

Background: The aim of this work was to evaluate the narrow anterior chamber angle (ACA) in Chinese patients by anterior segment optical coherence tomography (As-OCT). Methods: Eighty right eyes of 80 consecutive patients with a shallow peripheral anterior chamber but no peripheral anterior synechia were enrolled in this study. The ACA was observed by noncompression gonioscopy and classified according to the Shaffer grading system. The iridotrabecular contact (ITC) and trabecular-iris angle (T-I angle) were assessed by As-OCT examination. Results: Gonioscopic grade 0 and ITC were observed more frequently in the superior quadrant than the other quadrants (p < 0.02). The T-I angle was signiﬁcantly smaller superiorly and inferiorly than nasally and temporally (p < 0.01). The frequency of the ITC and T-I angle significantly declined when the gonioscopic grade was from 0 to 2 (p < 0.01). Logistic analysis showed that the axial length and refraction were related to the presence of ITC in more than two quadrants (p < 0.03). Conclusions: ITC was common in eyes with a shallow peripheral anterior chamber (superiorly, gonioscopic grade 0). Sites with wider gonioscopic grading tended to have a larger T-I angle. Axial length and refraction significantly impacted on the frequency of ITC.
Non-Virilizing Congenital Adrenal Hyperplasia in a Female Patient with a Novel HSD3B2 Mutation
Authors: Probst-Scheidegger Ursina , Udhane Sameer S. , l'Allemand Dagmar , Flück Christa E. , Camats Núria
Published: September 2016

Classic 3β-hydroxysteroid dehydrogenase type 2 (3β-HSD II) deficiency causes congenital adrenal hyperplasia with glucocorticoid, mineralocorticoid, and sex steroid deficiency. We present a female patient with congenital adrenal hyperplasia detected in newborn screening due to elevated 17OH-progesterone. Female external genitalia and non-measurable androgen levels elicited the suspicion of a defect early in the steroid cascade. Two loss-of-function HSD3B2 mutations (1 novel) were detected and confirmed in silico. We argue that in a girl with glucocorticoid and mineralocorticoid deficiency without virilization, 3β-HSD II deficiency is an important differential diagnosis. 17OH-progesterone may initially be elevated due to placental and peripheral activity of 3β-HSD I, whereas dehydroepiandrosterone may not be increased.
Incidence and Case Fatality at the County Level as Contributors to Geographic Disparities in Stroke Mortality
Authors: Labarthe Darwin R. , Howard George , Safford Monika M. , Howard Virginia J. , Judd Suzanne E. , Cushman Mary , Kissela Brett M. ,   for the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Investigators
Published: September 2016

Background: Is the high stroke mortality in the Southeastern parts of the United States driven by differences in stroke incidence or case-fatality? This question remains unanswered. Differences in incidence would underscore the need for stroke prevention, while differences in case fatality would call for improved stroke care. Methods: Quartiles of US counties were defined by stroke mortality, and this gradient was related with stroke incidence and stroke case fatality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, where 1,317 incident stroke events (of which 242 were fatal) occurred among 29,650 participants. Results: There was a significant (p = 0.0025) gradient of fatal stroke events in REGARDS (quartile 4 vs. quartile 1 (Q4/Q1) hazard ratio 1.95, 95% CI 1.35-2.81), demonstrating the consistency of REGARDS with national mortality data. The gradient for incident stroke (fatal + nonfatal) was also significant (p = 0.0023; Q4/Q1 hazard ratio 1.29, 95% CI 1.10-1.52). The gradient for stroke case-fatality was marginally significant (p = 0.058), though the OR for Q4/Q1 (1.71, 95% CI 1.13-2.25) was large. Conclusions: Both stroke incidence and case-fatality in REGARDS appear to be contributing, underscoring the need for strengthening both stroke prevention and acute stroke care in order to reduce the disparity.
Tissue Reactions to Heterogenic and Allogeneic Acellular Dermal Matrix Mesh Placed in the Vesicovaginal Space in a Rabbit Model
Authors: Yao Ying , Zhang Kun , Han Jinsong , Yang Junfang , Zhu Fuli , Wang Yiting , Qiao Jie
Published: September 2016

Background and Aim: This study is aimed at investigating the tissue reactions of heterogenic and allogeneic acellular dermal matrix (ADM) mesh implanted in the vesicovaginal space in a rabbit model. Methods: Twenty eight rabbits were implanted with heterogenic or allogeneic mesh, respectively, in the vesicovaginal space, and 4 served as the no-implantation control group. Rabbits were sacrificed at 7, 30, and 90 days after implantation. Histopathological study and immunohistochemical examination for collagen were performed. Results: Heterogenic but not allogeneic mesh was identifiable at 90 days. In the allogeneic group, neovascularization was observed from day 7 after implantation. A chronic inflammatory reaction was noted in the heterogenic group at 30 days that decreased at 90 days. Inflammation was less in the allogeneic group, but giant cells and fibroblasts were present. With respect to collagen, the heterogenic mesh remained structurally unchanged at 90 days, while new collagen fibers were observed in the allogeneic group from day 7. Conclusion: The immunological outcomes of heterogenic and allogeneic ADM mesh are different. Heterogenic mesh induces a chronic inflammatory reaction at day 30 after implantation, and maintains its original form longer. Allogeneic mesh is associated with new collagen generation, but degrades earlier.
Renal Interstitial Fibrosis: An Imperfect Predictor of Kidney Disease Progression in Some Patient Cohorts
Authors: Menn-Josephy Hanni , Lee Carol S. , Nolin Angela , Christov Marta , Rybin Denis V. , Weinberg Janice M. , Henderson Joel , Bonegio Ramon , Havasi Andrea
Published: September 2016

Background: The extent of interstitial fibrosis on kidney biopsy is regarded as a prognostic indicator and guide to treatment. Patients with extensive fibrosis are assigned to supportive treatments with the expectation that they have advanced beyond the point at which immunosuppressive or other disease-modifying therapies would be of benefit. Our study highlights some of the limitations of using interstitial fibrosis to predict who will develop end-stage renal disease (ESRD). Methods: Analysis of 434 consecutive renal biopsies performed between 2001 and 2012 at a single center. We assessed the influence of various clinical factors along with fibrosis as predictors of ESRD and dialysis-free survival in various patient groups. Results: Interstitial fibrosis performed well overall as a predictor of progression to dialysis. On average, patients with >50% fibrosis progressed more rapidly than those with either 25-49 or 0-24% fibrosis with a median time to dialysis of 1.2, 6.5 and >10 years, respectively. In contrast, interstitial fibrosis was of less value as a predictor of disease progression in a subset of cases that included patients over the age of 70 and those with diabetic nephropathy on biopsy. Surprisingly, 13.9% of patients with normal renal function had 25-49% fibrosis and 5% had more than 50% fibrosis on biopsy, and 5 years after undergoing biopsy 21% of patients with >50% fibrosis still remained dialysis free. Conclusion: Renal fibrosis is an imperfect prognostic indicator for the development of ESRD and caution should be exercised in applying it too rigidly, especially in elderly or diabetic patients.
Should We Always Defer Treatment of Kidney Disease When There Is Extensive Interstitial Fibrosis on Biopsy?
Authors: Hommos Musab S. , Rule Andrew D.
Published: September 2016

Severity of interstitial fibrosis and tubular atrophy (IFTA) seen on kidney biopsy has been used by nephrologist as prognostic marker of kidney disease. While IFTA is a very strong predictor of kidney failure, some patients with severe fibrosis will still not progress to kidney failure within 5 years. Treatment of underlying kidney disease in select patients with severe IFTA should be considered when risks of treatment are reasonable despite the low potential for benefit.
Serotonin Transporter Binding in the Diencephalon Is Reduced in Insulin-Resistant Obese Humans
Authors: Versteeg Ruth I. , Koopman Karin E. , Booij Jan , Ackermans Mariëtte T. , Unmehopa Unga A. , Fliers Eric , la Fleur Susanne E. , Serlie Mireille J.
Published: September 2016

Background: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. Methods: We performed a case-control study in insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using 123I- FP-CIT single-photon emission computed tomography. We assessed insulin sensitivity using the homeostatic model assessment of insulin resistance. Results: BMI did not differ between the IRO and ISO subjects. SERT binding in the diencephalon was significantly lower in IRO than in ISO subjects, but was not different between lean and obese subjects. SERT binding in the hypothalamus tended to be reduced in obese versus lean subjects, but was not different between IRO and ISO subjects. Striatal DAT binding was similar between lean and obese subjects as well as between ISO and IRO subjects. Conclusions: We conclude that SERT binding in the diencephalon is reduced in insulin-resistant subjects independently of body weight, while hypothalamic SERT binding tends to be lower in obesity, with no difference between insulin-resistant and insulin-sensitive subjects. This suggests that the metabolic perturbations associated with obesity independently affect SERT binding within the diencephalon.
Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice
Authors: Camm A. , Coleman Craig , Tamayo CAPT , Beyer-Westendorf Jan
Published: September 2016

Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.
Spotlight on real-world evidence for the treatment of DVT: XALIA
Authors: Turpie Alexander , Ageno Walter
Published: September 2016

Venous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.
ДИСТАНЦІЙНЕ НАВЧАННЯ СУЧАСНИМ МЕДИЧНИМ ТЕХНОЛОГІЯМ ЗА ДОПОМОГОЮ СТРУКТУРОВАНИХ І ФОРМАЛІЗОВАНИХ ДЕКЛАРАТИВНИХ
Authors: Denysenko S. V.
Published: September 2016

There is not enough іп most cases to provide syntactic interoperabi1i1y for interaction between the different educational systems іп the Intranet / Internet networks. Today there is virtually no educational systems that solve this problem by using a single dictionary (taxonomy) with descriptions of the data used (ontology). So, that is the problem of lack of clear semantic definitions prevents the unification of educational systems from different manufacturers.

The article first considered the possibility of using ontological representations for selection of assisted reproductive technologies for infertility. Specific criteria for assessing the effectiveness of ontological structures are proposed. In the development of ontology to summarize knowledge of assisted reproductive technology used five-level scheme. The first level is reserved for basic information, where we use all theoretically possible terms and concepts, and the second - is designed to solve diagnostic problems, the third - to address the medical, therapeutic management of fourth-and fifth process - educational technology. A scheme for data clustering survey of patients requiring the use of assisted reproductive technologies, containing 11 clusters of attributes.

The possibilities of practical use of medical ontology’s are discussed.
СТРАТЕГІЯ ВДОСКОНАЛЕННЯ МЕДИЧНОГО СТРАХУВАННЯ НА ОСНОВІ ПОКАЗНИКІВ ЯКОСТІ НАДАННЯ МЕДИЧНОЇ ДОПОМОГИ
Authors: Dzhundubaieva S. O.
Published: September 2016

Issues of improving the health insurance through the creation of quality systems of care are discussed. Particular attention is paid to the identification of medical errors, and that was the aim of this work. Despite the complexity of the process of objectification, examines possible solutions to this problem, and the impact on the risk of the insurance business are analyzed. The prospects of normative-legal and information-mathematical strategies to identify medical errors are considered. In particular, issues of professional liability insurance, which allows a civilized manner to resolve conflicts between doctors and patients, are examined. At the same time, the direct use of this approach meets with incomprehension medical staff a number of provisions, such as the subject of insurance, the allocation of responsibility between the performers of medical appointments, as well as mechanisms of the effect of the law on the reduction of medical errors.

Today, it seems more practical use of information-based approaches for identifying medical errors. It is emphasized that the starting point of the work to improve the quality of care are the technologies of identifying and addressing its root causes. We consider some
formal algorithms, “Deming wheel,” the organizing principle of the sample survey method, the method of screening sheet, the method of histograms, Pareto charts and others. Note that the process of approach adversely affects its efficiency. Therefore, the most promising should recognize the use of ontological ideas about the dynamics of the pathological process and its standardization.
РЕЗУЛЬТАТИ ДОСЛІДЖЕННЯ ПОКАЗНИКІВ ГЕМОДИНАМІКИ В ЯКОСТІ МАРКЕРІВ ВКЛЮЧЕННЯ ДО ГРУП РИЗИКУ РОЗВИТКУ УСКЛАДНЕНЬ У ХВОРИХ З ГІПЕРТЕНЗІЄЮ: АНАЛІЗ НА ОСНОВІ ROC-КРИВОЇ
Authors: Selskyy P. R.
Published: September 2016

The paper suggests an optimization method for the developing disease prognosis at the primary health care level.

The hemodynamic indices in primary and re-examination as token inclusion to vulnerable groups of health deterioration and developing
ІНФОРМАЦІЙНА СИСТЕМА ДЛЯ МЕДИКО-ГЕНЕТИЧНОЇ ЛАБОРАТОРІЇ
Authors: Stetsyuk V. Z. , Sawickiy A. I. , Ivanova T. P. , Olhovich N. V. , Luhovskii Y. O.
Published: September 2016

In article describes an application that was developed to optimize laboratory staff and doctors work. The article begins with showing which laboratories materials and internal processes were used in investigation. Then describes how based on this result application was developed.

The program provides functionality that can be divided into several parts: saving, editing and deleting data, viewing data, search, data processing, creating documents, authorization, distributed work. These functions described enough to understand how they present in application, which data they are using and which output they produce. Also describes advantages for each functionality and shows how it helps doctors and laboratory staff.
МЕХАНІЗМИ ЗАБЕЗПЕЧЕННЯ ТА ЗАХИСТУ ПРАВ ПАЦІЄНТІВ В УКРАЇНІ
Authors: Yaremenko N. V.
Published: September 2016

The questions of research areas for the protection of patients' rights are considered. It is emphasized that despite the recognition by the Constitution and laws of Ukraine human life and health as the highest social value proper mechanisms for patient's fundamental rights enforcement has not been established in Ukraine. The creation of a special law that would determine the mechanisms of implementation and protection of citizens' rights to health and medical care is proposed.

 
Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points
Authors: Greene Stephen J. , Hernandez Adrian F. , Sun Jie-Lena , Metra Marco , Butler Javed , Ambrosy Andrew P. , Ezekowitz Justin A. , Starling Randall C. , Teerlink John R. , Schulte Phillip J. , Voors Adriaan A. , Armstrong Paul W. , O’Connor Christopher M. , Mentz Robert J.
Published: September 2016

Background—

Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear.

Methods and Results—

We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5–23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89–0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01–1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98–1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96–0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98–1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction
P
<0.01).

Conclusions—

In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00475852.
Ultrasonic Assessment of Myocardial Microstructure in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy
Authors: Hiremath Pranoti , Lawler Patrick R. , Ho Jennifer E. , Correia Andrew W. , Abbasi Siddique A. , Kwong Raymond Y. , Jerosch-Herold Michael , Ho Carolyn Y. , Cheng Susan
Published: September 2016

Background—

The noninvasive assessment of altered myocardium in patients with genetic mutations that are associated with hypertrophic cardiomyopathy (HCM) remains challenging. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy.

Methods and Results—

We studied 3 groups of genotyped individuals: sarcomere mutation carriers with left ventricular hypertrophy (clinical HCM; n=36), mutation carriers with normal left ventricular wall thickness (subclinical HCM; n=28), and healthy controls (n=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including cardiac magnetic resonance measures of interstitial fibrosis (extracellular volume fraction), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation–adjusted analyses, the SIC was quantitatively different across subjects with overt HCM, subclinical HCM, and healthy controls (
P
<0.001). Compared with controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (
P
<0.001 for both). The SIC was significantly correlated with extracellular volume (
r
=0.72;
P
<0.01), with left ventricular mass and E′ velocity (
r
=0.45, -0.60, respectively;
P
<0.01 for both), and with serum NTproBNP levels (
r
=0.36;
P
<0.001).

Conclusions—

Our findings suggest that the SIC could serve as a noninvasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and to evaluate the effects of interventions.
Smoking and Cardiac Structure and Function in the Elderly
Authors: Nadruz Wilson , Claggett Brian , Gonçalves Alexandra , Querejeta-Roca Gabriela , Fernandes-Silva Miguel M. , Shah Amil M. , Cheng Susan , Tanaka Hirofumi , Heiss Gerardo , Kitzman Dalane W. , Solomon Scott D.
Published: September 2016

Background—

Cigarette smoking has been associated with higher risk of incident heart failure independent of coronary artery disease, but the impact of tobacco use on cardiac structure and function in the general population is uncertain. This study evaluated the relationship between smoking and echocardiographic measures in a large elderly cohort.

Methods and Results—

We studied 4580 participants free of overt coronary artery disease, heart failure, and significant valvular disease from the fifth visit of the ARIC study (Atherosclerosis Risk in Communities) who underwent transthoracic echocardiography. Participants were classified into 3 categories based on self-reported smoking habits: never (43.2%), former (50.5%), and current smokers (6.3%). Pack-years and years of smoking were also estimated. Compared with never smokers, current smokers had greater left ventricular (LV) mass index (80.4±1.1 versus 76.7±0.4 g/m
2
;
P
<0.001), LV mass/volume ratio (1.93±0.03 versus 1.83±0.03 g/mL;
P
<0.001), higher prevalence of LV hypertrophy (15% versus 9%;
P
=0.008), and worse diastolic function, as reflected by higher E/E′ ratio (11.7±0.2 versus 10.9±0.1;
P
<0.001), after adjusting for potential confounding factors. In contrast, former smokers showed similar echocardiographic features when compared with never smokers. Furthermore, estimated pack-years and years of smoking, measures of cumulative cigarette exposure, were associated with greater LV mass index, LV mass/volume ratio, and worse diastolic function (higher E/E′ ratio) in current smokers after multivariable analysis (all
P
<0.01).

Conclusions—

Active smoking and cumulative cigarette exposure were associated with subtle alterations in LV structure and function in an elderly, community-based population free of overt coronary artery disease and heart failure.
Variation in Hospital Risk–Adjusted Mortality Rates Following Transcatheter Aortic Valve Replacement in the United States
Authors: O’Brien Sean M. , Cohen David J. , Rumsfeld John S. , Brennan J. Matthew , Shahian David M. , Dai David , Holmes David R. , Hakim Rosemarie B. , Thourani Vinod H. , Peterson Eric D. , Edwards Fred H.
Published: September 2016

Background—

The use of transcatheter aortic valve replacement (TAVR) to treat aortic stenosis in the United States is growing, yet little is known about the variation in procedural outcomes in community practice. We developed a TAVR in-hospital mortality risk model and used it to quantify variation in mortality rates across United States (US) TAVR centers.

Methods and Results—

We analyzed data from 22 248 TAVR procedures performed at 318 sites participating in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry (November 2011 to October 2014). A Bayesian hierarchical model was developed to estimate hospital-specific risk-adjusted mortality rates adjusting for 40 patient baseline factors. A total of 1130 in-hospital deaths (5.1%) were observed. Reliability-adjusted risk-adjusted mortality rate estimates ranged from 3.4% to 7.7% with an interquartile range of 4.8% to 5.4%. A patient’s predicted odds of dying was 80% higher if treated by a hospital 1 standard deviation above the mean compared with a hospital 1 standard deviation below the mean (odds ratio =1.8; 95% credible interval, 1.4%–2.2%).

Conclusions—

Risk modeling of TAVR in-hospital mortality revealed variation in risk-adjusted mortality rates during the US early commercial experience. Transcatheter Valve Therapy Registry analyses using this model will support research, feedback reporting, and the identification of factors associated with quality.
Regional Learning Collaboratives Produce Rapid and Sustainable Improvements in Stroke Thrombolysis Times
Authors: Prabhakaran Shyam , Lee Jungwha , O’Neill Kathleen
Published: September 2016

Background—

Reduction in door-to-needle (DTN) times in patients with acute ischemic stroke treated with tissue-type plasminogen activator is associated with improved outcomes. We hypothesized that a learning collaborative would rapidly reduce DTN times at Chicago’s primary stroke centers.

Methods and Results—

We analyzed data from all adult patients with out-of-hospital ischemic stroke hospitalized between January 1, 2010 and March 31, 2015 and who received tissue-type plasminogen activator in the emergency department at 15 primary stroke centers in Chicago and 15 primary stroke centers in St. Louis. We implemented a structured learning collaborative in Chicago in quarter 1 of 2013 that included (1) a quality improvement leader, (2) stroke content expert, (3) multidisciplinary teams from each site, (4) a targeted goal for the program (DTN time <60 minutes in >50% of patients treated with tissue-type plasminogen activator), and (5) face-to-face meetings with on-site visits. We used interrupted time-series analysis to compare the impact of the learning collaborative on DTN times in Chicago pre- and post implementation and also concurrently versus St. Louis. We prespecified adjustment for mode of arrival, emergency medical services prenotification, and onset-to-arrival times.
P
values less than 0.05 were considered significant. In adjusted analysis, the reduction in DTN time within 1 quarter of implementation was 15.5 minutes (
P
=0.046) at Chicago sites versus 1.17 minutes at St. Louis sites (
P
=0.601).

Conclusions—

Using a learning collaborative model at Chicago’s 15 primary stroke centers, we observed major reductions in DTN times within 1 quarter of implementation. Regional collaboration and best practices sharing should be a model for rapid and sustainable system-wide quality improvement.
Blood Flow Into Basilar Tip Aneurysms
Authors: Sugiyama Shin-ichiro , Niizuma Kuniyasu , Sato Kenichi , Rashad Sherif , Kohama Misaki , Endo Hidenori , Endo Toshiki , Matsumoto Yasushi , Ohta Makoto , Tominaga Teiji
Published: September 2016

Background and Purpose—

Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms.

Methods—

We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a follow-up of >1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics.

Results—

Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density <30% were independent and significant predictors for the recanalization of coiled aneurysms. Additional investigation revealed that a small branch angle formed by the basilar artery and the posterior cerebral artery increased blood flow into the aneurysm.

Conclusions—

The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.
Antiphospholipid Antibodies and the Risk of Stroke in Urban and Rural Tanzania
Authors: de Mast Quirijn , Molhoek Jessica E. , van der Ven André J. , Gray William K. , de Groot Philip G. , Jusabani Ahmed , Mugusi Ferdinand , Urbanus Rolf T. , Walker Richard W.
Published: September 2016

Background and Purpose—

The burden of stroke is high in sub-Saharan Africa, and improved knowledge of risk factors is needed. Antiphospholipid antibodies are a common acquired stroke risk factor in young individuals. Antiphospholipid antibodies may be induced by infectious diseases. Sub-Saharan Africa has a high infectious burden, and we analyzed the contribution of antiphospholipid antibodies to the risk of stroke in an incident population from rural and urban Tanzania.

Methods—

Stroke cases and age- and sex-matched community-acquired controls from the rural Hai district and urban Dar-es-Salaam areas of Tanzania were recruited in a wider study of stroke incidence between June 2003 and June 2006. Lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I, and antiphosphatidylserine/prothrombin antibodies were determined in stored plasma, as well as IgG antibodies against
Treponema pallidum
.

Results—

Data from 158 stroke cases and 369 controls were analyzed. Thirty cases (19%) and 4 controls (1%) had a lupus anticoagulant (odds ratio, 20.8; 95% confidence interval, 7.2–60.5). Anticardiolipin IgG was the only other antiphospholipid antibody subtype associated with increased stroke risk (odds ratio, 2.1; 95% confidence interval, 1.0–4.3), but this association disappeared when corrected for IgG antibodies against
Treponema pallidum
results. The prevalence of anti-β2-glycoprotein I IgG antibodies in the Tanzanian healthy population was high when Dutch cutoff values were applied (67%), whereas presence of anti-β2-glycoprotein I IgM was associated with a reduced stroke risk (odds ratio 0.3; 95% confidence interval, 0.1–1.1).

Conclusions—

The presence of lupus anticoagulant is a strong, and to date unrecognized, risk factor for stroke in Tanzania, especially in young and middle-aged individuals.
Applicability of Clinical Trials in an Unselected Cohort of Patients With Intracerebral Hemorrhage
Authors: Hansen Björn M. , Ullman Natalie , Norrving Bo , Hanley Daniel F. , Lindgren Arne
Published: September 2016

Background and Purpose—

Patient selection in clinical trials on intracerebral hemorrhage (ICH) affects overall applicability of results. We estimated eligibility for completed, ongoing, and planned clinical trials in an unselected cohort of patients with ICH.

Methods—

Large clinical ICH trials were identified using trial registration databases. Each trial’s inclusion criteria were applied to a consecutive group of patients with ICH from the prospective hospital-based Lund Stroke Register. Survival status was obtained from the National Census Office and 90-day poor functional outcome (modified Rankin Scale ≥4) from the Swedish Stroke Register or medical files.

Results—

Among 253 patients with ICH, estimated eligibility proportions ranged between 2% and 36% for the 11 identified clinical trials. Patients not eligible for any trial (n=96) had more intraventricular hemorrhage, lower baseline level of consciousness, higher rates of cerebellar ICH, and lower rates of lobar ICH (
P
≤0.001). Thirty-day case fatality for noneligible patients was 54% versus 18% among patients eligible in ≥1 trial (95% confidence interval, 44%–64% versus 13%–25%;
P
<0.001). Noneligible ICH patients more frequently had poor functional outcome (75% versus 48%; 95% confidence interval, 65%–83% versus 40%–56%;
P
<0.001).

Conclusions—

There is large variation in proportions of patients with ICH eligible for inclusion in clinical trials and over a third of patients with ICH are not eligible for any trial.
Rhythmic Activity and Individual Variability in Recognition Memory: Theta Oscillations Correlate with Performance whereas Alpha Oscillations Correlate with ERPs
Authors: Chen Yvonne Y. , Caplan Jeremy B.
Published: September 2016

During study trials of a recognition memory task, alpha (∼10 Hz) oscillations decrease, and concurrently, theta (4–8 Hz) oscillations increase when later memory is successful versus unsuccessful (subsequent memory effect). Likewise, at test, reduced alpha and increased theta activity are associated with successful memory (retrieval success effect). Here we take an individual-differences approach to test three hypotheses about theta and alpha oscillations in verbal, old/new recognition, measuring the difference in oscillations between hit trials and miss trials. First, we test the hypothesis that theta and alpha oscillations have a moderately mutually exclusive relationship; but no support for this hypothesis was found. Second, we test the hypothesis that theta oscillations explain not only memory effects within participants, but also individual differences. Supporting this prediction, durations of theta (but not alpha) oscillations at study and at test correlated significantly with d′ across participants. Third, we test the hypothesis that theta and alpha oscillations reflect familiarity and recollection processes by comparing oscillation measures to ERPs that are implicated in familiarity and recollection. The alpha-oscillation effects correlated with some ERP measures, but inversely, suggesting that the actions of alpha oscillations on memory processes are distinct from the roles of familiarity- and recollection-linked ERP signals. The theta-oscillation measures, despite differentiating hits from misses, did not correlate with any ERP measure; thus, theta oscillations may reflect elaborative processes not tapped by recollection-related ERPs. Our findings are consistent with alpha oscillations reflecting visual inattention, which can modulate memory, and with theta oscillations supporting recognition memory in ways that complement the most commonly studied ERPs.
Sleep Spindles and Intellectual Ability: Epiphenomenon or Directly Related?
Authors: Fang Zhuo , Sergeeva Valya , Ray Laura B. , Viczko Jeremy , Owen Adrian M. , Fogel Stuart M.
Published: September 2016

Sleep spindles—short, phasic, oscillatory bursts of activity that characterize non-rapid eye movement sleep—are one of the only electrophysiological oscillations identified as a biological marker of human intelligence (e.g., cognitive abilities commonly assessed using intelligence quotient tests). However, spindles are also important for sleep maintenance and are modulated by circadian factors. Thus, the possibility remains that the relationship between spindles and intelligence quotient may be an epiphenomenon of a putative relationship between good quality sleep and cognitive ability or perhaps modulated by circadian factors such as morningness–eveningness tendencies. We sought to ascertain whether spindles are directly or indirectly related to cognitive abilities using mediation analysis. Here, we show that fast (13.5–16 Hz) parietal but not slow (11–13.5 Hz) frontal spindles in both non-rapid eye movement stage 2 sleep and slow wave sleep are directly related to reasoning abilities (i.e., cognitive abilities that support “fluid intelligence,” such as the capacity to identify complex patterns and relationships and the use of logic to solve novel problems) but not verbal abilities (i.e., cognitive abilities that support “crystalized intelligence”; accumulated knowledge and experience) or cognitive abilities that support STM (i.e., the capacity to briefly maintain information in an available state). The relationship between fast spindles and reasoning abilities is independent of the indicators of sleep maintenance and circadian chronotype, thus suggesting that spindles are indeed a biological marker of cognitive abilities and can serve as a window to further explore the physiological and biological substrates that give rise to human intelligence.
Frontostriatal Contribution to the Interplay of Flexibility and Stability in Serial Prediction
Authors: Trempler Ima , Schiffer Anne-Marike , El-Sourani Nadiya , Ahlheim Christiane , Fink Gereon R. , Schubotz Ricarda I.
Published: September 2016

Surprising events may be relevant or irrelevant for behavior, requiring either flexible adjustment or stabilization of our model of the world and according response strategies. Cognitive flexibility and stability in response to environmental demands have been described as separable cognitive states, associated with activity of striatal and lateral prefrontal regions, respectively. It so far remains unclear, however, whether these two states act in an antagonistic fashion and which neural mechanisms mediate the selection of respective responses, on the one hand, and a transition between these states, on the other. In this study, we tested whether the functional dichotomy between striatal and prefrontal activity applies for the separate functions of updating (in response to changes in the environment, i.e., switches) and shielding (in response to chance occurrences of events violating expectations, i.e., drifts) of current predictions. We measured brain activity using fMRI while 20 healthy participants performed a task that required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press while sequence omissions (drifts) had to be ignored. We further varied the probability of switches and drifts to assess the neural network supporting the transition between flexible and stable cognitive states as a function of recent performance history in response to environmental demands. Flexible switching between models was associated with activation in medial pFC (BA 9 and BA 10), whereas stable maintenance of the internal model corresponded to activation in the lateral pFC (BA 6 and inferior frontal gyrus). Our findings extend previous studies on the interplay of flexibility and stability, suggesting that different prefrontal regions are activated by different types of prediction errors, dependent on their behavioral requirements. Furthermore, we found that striatal activation in response to switches and drifts was modulated by participants' successful behavior toward these events, suggesting the striatum to be responsible for response selections following unpredicted stimuli. Finally, we observed that the dopaminergic midbrain modulates the transition between different cognitive states, thresholded by participants' individual performance history in response to temporal environmental demands.
On the Role of the Inferior Intraparietal Sulcus in Visual Working Memory for Lateralized Single-feature Objects
Authors: Brigadoi Sabrina , Cutini Simone , Meconi Federica , Castellaro Marco , Sessa Paola , Marangon Mattia , Bertoldo Alessandra , Jolicœur Pierre , Dell'Acqua Roberto
Published: September 2016

A consolidated practice in cognitive neuroscience is to explore the properties of human visual working memory through the analysis of electromagnetic signals using cued change detection tasks. Under these conditions, EEG/MEG activity increments in the posterior parietal cortex scaling with the number of memoranda are often reported in the hemisphere contralateral to the objects' position in the memory array. This highly replicable finding clashes with several reported failures to observe compatible hemodynamic activity modulations using fMRI or fNIRS in comparable tasks. Here, we reconcile this apparent discrepancy by acquiring fMRI data on healthy participants and employing a cluster analysis to group voxels in the posterior parietal cortex based on their functional response. The analysis identified two distinct subpopulations of voxels in the intraparietal sulcus (IPS) showing a consistent functional response among participants. One subpopulation, located in the superior IPS, showed a bilateral response to the number of objects coded in visual working memory. A different subpopulation, located in the inferior IPS, showed an increased unilateral response when the objects were displayed contralaterally. The results suggest that a cluster of neurons in the inferior IPS is a candidate source of electromagnetic contralateral responses to working memory load in cued change detection tasks.
Neural Quadratic Discriminant Analysis: Nonlinear Decoding with V1-Like Computation
Authors: Pagan Marino , Simoncelli Eero P. , Rust Nicole C.
Published: September 2016

Linear-nonlinear (LN) models and their extensions have proven successful in describing transformations from stimuli to spiking responses of neurons in early stages of sensory hierarchies. Neural responses at later stages are highly nonlinear and have generally been better characterized in terms of their decoding performance on prespecified tasks. Here we develop a biologically plausible decoding model for classification tasks, that we refer to as neural quadratic discriminant analysis (nQDA). Specifically, we reformulate an optimal quadratic classifier as an LN-LN computation, analogous to “subunit” encoding models that have been used to describe responses in retina and primary visual cortex. We propose a physiological mechanism by which the parameters of the nQDA classifier could be optimized, using a supervised variant of a Hebbian learning rule. As an example of its applicability, we show that nQDA provides a better account than many comparable alternatives for the transformation between neural representations in two high-level brain areas recorded as monkeys performed a visual delayed-match-to-sample task
Neural Mechanism to Simulate a Scale-Invariant Future
Authors: Shankar Karthik H. , Singh Inder , Howard Marc W.
Published: September 2016

Predicting the timing and order of future events is an essential feature of cognition in higher life forms. We propose a neural mechanism to nondestructively translate the current state of spatiotemporal memory into the future, so as to construct an ordered set of future predictions almost instantaneously. We hypothesize that within each cycle of hippocampal theta oscillations, the memory state is swept through a range of translations to yield an ordered set of future predictions through modulations in synaptic connections. Theoretically, we operationalize critical neurobiological findings from hippocampal physiology in terms of neural network equations representing spatiotemporal memory. Combined with constraints based on physical principles requiring scale invariance and coherence in translation across memory nodes, the proposition results in Weber-Fechner spacing for the representation of both past (memory) and future (prediction) timelines. We show that the phenomenon of phase precession of neurons in the hippocampus and ventral striatum correspond to the cognitive act of future prediction.