bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protective Role of HLA-DRB113 in Autoimmune Diseases
Authors: Bettencourt Andreia , Carvalho Cláudia , Leal Bárbara , Brás Sandra , Lopes Dina , Martins da Silva Ana , Santos Ernestina , Torres Tiago , Almeida Isabel , Farinha Fátima , Barbosa Paulo , Marinho António , Selores Manuela , Correia João , Vasconcelos Carlos , Costa Paulo P. , da Silva Berta Martins
Published: October 2015

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB115 (OR = 2.17) and HLA-DRB103 (OR = 1.81) alleles with MS, HLA-DRB103 with SLE (OR = 2.49), HLA-DRB101 (OR = 1.79) and HLA-DRB104 (OR = 2.81) with RA, HLA-DRB107 with Ps + PsA (OR = 1.79), HLA-DRB101 (OR = 2.28) and HLA-DRB108 (OR = 3.01) with SSc, and HLA-DRB103 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB113 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB113 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB113, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB113 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.
Long Non-Coding RNA Expression Profiling in Aging Rats with Erectile Dysfunction
Authors: Pan Lianjun , Ma Jiehua , Pan Feng , Zhao Dan , Gao Jianping
Published: October 2015

Background/Aims: Erectile dysfunction (ED) in aged people remains a topic of interest to andrological physicians. Long non-coding RNAs (lncRNAs), which form the largest group of non-coding RNAs, have been shown to regulate various biological processes. The function of lncRNAs in age-related erectile dysfunction (A-ED) pathogenesis remains poorly understood. Methods: This study aims to assess the differential expression profiles of mRNAs and lncRNAs between A-ED and normal control (NC) samples. Using a second-generation lncRNA microarray, we detected a total of 8,744 lncRNAs and 13,585 coding transcripts. Results: We identified 608 up-regulated and 406 down-regulated lncRNAs in A-ED compared with NC samples, by setting a filter of fold-change >2.0. Gene Ontology and pathway analysis revealed that a muscle contraction disorder induced by abnormal ion channels might play a critical role in the pathogenesis of A-ED. Conclusion: Our results show significantly altered expression profiles of lncRNAs and mRNAs between A-ED and NC. This study may provide information for further research on A-ED and may be helpful for finding a new therapeutic target for A-ED.
MiR-429 Induces Gastric Carcinoma Cell Apoptosis Through Bcl-2
Authors: Zhu Ping , Zhang Jingping , Zhu Jianfei , Shi Jun , Zhu Qiuwei , Gao Yuanyuan
Published: October 2015

Background/Aims: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of gastric carcinoma (GC). MiR-429 has been recently reported to inhibit GC growth, but the underlying mechanisms are not clear. Methods: Here, we studied the levels of miR-429 and anti-apoptotic protein Bcl-2 in GC specimens. We performed bioinformatics analyses and used luciferase-reporter assay to analyze the relationship between miR-429 and Bcl-2 in GC cells. Cell survival upon Fluorouracil treatment was analyzed in a CCK assay. Cell apoptosis was measured by flow cytometry based FITC Annexin V apoptosis detection assay. Results: MiR-429 levels were significantly decreased and Bcl-2 levels were significantly increased in GC specimens, compared to the paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-429 and Bcl-2 inversely correlated in GC specimens. MiR-429-low subjects had an overall inferior survival, compared to miR-429-high subjects. Bioinformatics analyses showed that miR-429 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Overexpression of miR-429 inhibited Bcl-2-mediated cell survival against apoptosis induced by Fluorouracil, while depletion of miR-429 augmented it. Conclusion: Our data suggest that miR-429 suppression in GC promotes Bcl-2-mediated cancer cell survival against chemotherapy-induced cell death. Re-expression of miR-429 levels in GC cells may enhance cancer apoptosis during chemotherapy.
Amyloidosis of the Breast: Three Different and Unusual Presentations of a Rare Entity
Authors: Herrero Laura , Naranjo-Hans Dolores , Solé Manel , Santamaría Gorane , Bargalló Xavier , Velasco Martín , Fernández Pedro Luis
Published: October 2015

Background: Amyloidosis involving the breast is a rare finding and it may present as a solitary mass called 'amyloid tumor'. According to the largest case series, the amyloid deposits are usually of the AL type (commonly κ light chain). Methods: We report 3 cases diagnosed at our institution in the period from 2000 to 2015. Radiological, histological and immunohistochemical studies were performed. Results and Conclusions: Together with a case presenting in a patient with multiple myeloma, we describe 2 unique presentations including 1 associated with CREST syndrome in a patient with a previous history of breast carcinoma and another, also associated with cancer, with transthyretin deposits in a woman with a TTR gene mutation and a family history of familial amyloidotic polyneuropathy. These cases are an example of the vast heterogeneity of this disorder regarding its clinical presentation, the type of amyloid deposits and other diseases associated with breast amyloidosis.
DWI Lesion Patterns Predict Outcome in Stroke Patients with Thrombolysis
Authors: Liu Dezhi , Scalzo Fabien , Starkman Sidney , Rao Neal M. , Hinman Jason D. , Kim Doojin , Ali Latisha K. , Saver Jeffrey L. , Noorian Ali Reza , Ng Kwan , Liang Conrad , Sheth Sunil A. , Yoo Bryan , Liu Xinfeng , Liebeskind David S. ,   on behalf of the UCLA-Jinling Neurovascular Imaging Research Collaborators
Published: October 2015

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis. Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns. Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days. Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047). Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients.
Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio
Authors: Amory Colum F. , Levine Steven R. , Brey Robin L. , Gebregziabher Mulugeta , Tuhrim Stanley , Tilley Barbara C. , Simpson Ann-Catherin C. , Sacco Ralph L. , Mohr Jay P. ,   for the APASS-WARSS Collaborators
Published: October 2015

Background: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. Methods: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-β2-glycoprotein-I (anti-β2GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results: Persistent anti-β2GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-β2GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-β2GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. Conclusions: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β2GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.
Improving Outcomes Achieved by a New Stroke Program in Hungary
Authors: Égi Csilla , Horváth Júlia , Hahn Katalin , Kalman Bernadette , Betlehem József , Nagy Lajos
Published: October 2015

Background: Stroke is a devastating disease with increasing incidence and prevalence due to population aging. Even with the best care, a proportion of patients dies or is left with significant neurological and cognitive disability. Organization of stroke centers markedly improved outcomes worldwide. We initiated a ‘lysis alarm' program in September 2013 at our medical center. Methods: This is a retrospective review of electronic data from patients with acute ischemic stroke before (October 2012-June 2013) and after (October 2013-June 2014) the ‘lysis alarm' program was introduced at our medical center. Results: Prior to the introduction of the stroke program, there were only 19 thrombolysis procedures in 777 acute stroke patients in 9 months, while this figure rose to 32 thrombolysis procedures in 737 acute stroke patients after the initiation of the program. The ‘door-to-needle' time decreased from 88 to 71 min when the two study periods were compared. These changes were associated with decreased stroke mortality in patients receiving thrombolytic treatment (16% prior to the program and 9% during the program). In 2013, there were 1,439 thrombolysis procedures, representing 3.2% of all stroke cases throughout Hungary. After the introduction of the ‘lysis alarm' program, we have reached a 4% thrombolysis rate at our medical center. Conclusions: Our thrombolysis rate is higher than the national average, but still low compared to the rates of Western European countries. We are continuously working to enhance our stroke program. Here, we discuss those components that need to be further refined in order to improve stroke intervention and outcome.
Multifocal BRAFV600E-Mutated Melanoma in situ on the Foot
Authors: Iwama Eimei , Fujimura Taku , Kusakari Yoshiyuki , Haga Takahiro , Aiba Setsuya
Published: October 2015

Melanoma is an aggressive skin cancer that originates from melanocytes, and about one half of melanoma cases possess a BRAF mutation. Together with PD-L1 expression, the BRAFV600E mutation is one of the optimal therapeutic targets for the treatment of melanoma. In this report, we describe a case of multifocal melanoma in situ on the foot, which carried the p.V600E mutation in the BRAF gene. Interestingly, the spotted melanoma lesion is demarcated by normal skin, and in all spotted pigmented lesions, there were no signs of dermal invasion of melanoma cells or spontaneous regression. Our case presented atypical clinical features, which might correlate with the local mutations of BRAF gene and the immunological expression of PD-L1.
Flushing Out Carcinoid Syndrome: Beneficial Effect of the Anticancer Epigenetic Agent RRx-001 in a Patient with a Treatment-Refractory Neuroendocrine Tumor
Authors: Carter Corey A. , Degesys Aiste , Oronsky Bryan , Scicinski Jan , Caroen Scott Z. , Oronsky Arnold L. , Reid Tony , Cabrales Pedro , Roswarski Joe
Published: October 2015

Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms defined by the presence of cells with secretory granules and the potential to produce and release high levels of vasoactive peptides into the circulation, leading to severe flushing and diarrhea, which may adversely affect quality of life. This report presents the case of a 64-year-old man with chronic refractory diarrhea due to pulmonary NET treated with the experimental anticancer agent RRx-001 in a phase II trial called TRIPLE THREAT with subsequent resolution of his diarrhea.
Risk of major bleeding in patients with venous thromboembolism treated with rivaroxaban or with heparin and vitamin K antagonists
Authors: Ageno Walter , Rutjes Anne W. S. , Pap Akos F. , Büller Harry R. , Nisio Marcello Di
Published: October 2015

The study aim was to identify predictive factors for major bleeding in patients receiving the novel oral factor Xa inhibitor rivaroxaban or enoxaparin-vitamin K antagonists (VKAs) for the treatment of acute symptomatic venous thromboembolism. We analysed data from patients included in the phase III EINSTEIN DVT and EINSTEIN PE studies. Factors associated with major bleeding events were assessed with best subset variable selection using Cox proportional hazards regression model. Three time windows were considered, i. e. the initial three weeks, after the third week onwards, and the entire duration of the anticoagulant treatment. Model discrimination was estimated using the C-statistic and validated internally by bootstrap techniques. Major bleeding occurred in 40 (1.0 %) of 4130 patients receiving rivaroxaban and in 72 (1.7 %) of 4116 receiving enoxaparin/VKAs, with 44 % of the major bleeding events occurring in the first three weeks of treatment. Significant risk factors for major bleeding were older age, black race, low haemoglobin concentrations, active cancer, and antiplatelet or non-steroidal anti-inflammatory drug therapy. The discrimination of the model for major bleeding was high for the first three weeks (C-statistic 0.73), from the fourth week onwards (C-statistic 0.68), and the entire period of anticoagulant treatment (C-statistic 0.74). This analysis identified risk factors for major bleeding in patients receiving the novel oral anticoagulant rivaroxaban or enoxaparin/VKAs for the treatment of acute venous thromboembolism. The prognostic model based on the combination of identified risk factors may be informative to estimate the risk of major bleeding both during the initial and later phases of anticoagulation.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Smoking Paradox in Patients Hospitalized With Coronary Artery Disease or Acute Ischemic Stroke
Authors: Ali Syed F. , Smith Eric E. , Reeves Mathew J. , Zhao Xin , Xian Ying , Hernandez Adrian F. , Bhatt Deepak L. , Fonarow Gregg C. , Schwamm Lee H.
Published: October 2015

Background—

Smoking is a potent risk factor for coronary artery disease (CAD) and acute ischemic stroke (AIS), but there are numerous reports of lower in-hospital mortality among smokers versus nonsmokers hospitalized for these events.

Methods and Results—

We analyzed all consecutive patients hospitalized with a first index CAD (n=158 054) or AIS (n=899 295) event in Get With The Guidelines from 2002 to 2012; 20.4% of AIS and 30.4% of patients with CAD were past-year smokers. Multivariable models and age-stratified analyses were used to estimate the adjusted odds ratio of in-hospital mortality in smokers versus nonsmokers. Smokers were younger, more often male, with fewer vascular risk factors, and were more likely to be admitted to hospitals that were large, academic, or in the South. In-hospital mortality was significantly lower among smokers in both CAD (2.7% versus 5.2%;
P
<0.0001) and AIS (3.5% versus 5.8%;
P
<0.0001). The difference between unadjusted and adjusted odds ratios for smoking (0.57 versus 0.86 in CAD; 0.56 versus 0.86 in AIS) indicates the presence of substantial confounding by age and other covariates, but a significant association of past-year smoking remained.

Conclusions—

Among patients hospitalized with CAD and AIS, smoking is a risk factor for early age of onset, even among those with few vascular risk factors. The persistent association with lower in-hospital mortality after adjusted and stratified analyses probably represents residual unmeasured confounding, although a biological effect of smoking cannot be excluded. Further clinical and prospective population-based studies are needed to explore variables that contribute to outcomes in these patients.
Electronic Stroke CarePath
Authors: Katzan Irene L. , Fan Youran , Speck Micheal , Morton Johanna , Fromwiller Lauren , Urchek John , Uchino Ken , Griffith Sandra D. , Modic Michael
Published: October 2015

We describe the development, implementation, and outcomes of the first 2 years of the Electronic Stroke CarePath, an initiative developed for management of ischemic stroke patients in an effort to improve efficiency and quality of care for patients. The CarePath consists of care pathways for ischemic stroke that are integrated within the electronic health record. Patient-reported outcomes are collected using an external software platform. Documentation tools, order sets, and clinical decision support were designed to improve efficiency, optimize process measure adherence, and produce clinical data as a byproduct of care that are available for future analyses. Inpatient mortality and length of stay were compared before and after CarePath implementation in ischemic stroke patients after adjustment for case-mix. Postdischarge functional outcomes of patients with ischemic stroke were compared between the first 3 months of rollout and remainder of the study period. From January 2011 to December 2012, there were 1106 patients with ischemic stroke on the CarePath. There was a decline in inpatient mortality in patients with ischemic stroke, but not in control patients with intracerebral or subarachnoid hemorrhage. Completion rate of patient-reported questionnaires at postdischarge stroke follow-up was 72.9%. There was a trend toward improved functional outcomes at follow-up with CarePath implementation. Implementation of the Electronic Stroke CarePath is feasible and may be associated with a benefit in multiple different outcomes after ischemic stroke. This approach may be an important strategy for optimizing stroke care in the future.
Meta-Analysis of Randomized Controlled Trials Comparing the Long-Term Outcomes of Carotid Artery Stenting Versus Endarterectomy
Authors: Vincent Sophie , Eberg Maria , Eisenberg Mark J. , Filion Kristian B.
Published: October 2015

Background—

Stenting is an endovascular alternative to endarterectomy for the management of carotid stenosis, but its long-term safety and efficacy relative to endarterectomy remain unclear. Our objective was to compare the safety and efficacy of stenting with those of endarterectomy, with a particular focus on long-term outcomes, via meta-analysis of randomized controlled trials (RCTs).

Methods and Results—

We systematically searched PubMed, EMBASE, MEDLINE, and the Cochrane Library for RCTs with ≥50 patients that compared stenting with endarterectomy in patients with carotid stenosis. Periprocedural and long-term outcomes were assessed, with data pooled across RCTs using random-effects models. Eight RCTs were included in our meta-analysis (n=7091), with follow-up ranging from 2.0 to 10.0 years. When compared with endarterectomy, stenting was associated with an increased risk of periprocedural stroke (relative risk, 1.49, 95% confidence interval [CI], 1.11 to 2.01; risk difference, 1.7%; 95% CI, 0.3 to 3.0) but a decreased risk of periprocedural myocardial infarction (relative risk, 0.47; 95% CI, 0.29 to 0.78; risk difference, −0.4%; 95% CI, −0.8% to 0.1%). During long-term follow-up, stenting was associated with an increased risk of stroke (relative risk, 1.36; 95% CI, 1.16 to 1.61) and a composite end point of ipsilateral stroke, periprocedural stroke, or periprocedural death (relative risk, 1.45; 95% CI, 1.20 to 1.75).

Conclusions—

Although stenting has more favorable periprocedural outcomes with respect to myocardial infarction, the observed increased risk of stroke and death throughout follow-up with stenting suggests that endarterectomy remains the treatment of choice for carotid stenosis.
Quality of Care and Ischemic Stroke Risk After Hospitalization for Transient Ischemic Attack
Authors: O’Brien Emily C. , Zhao Xin , Fonarow Gregg C. , Schulte Phillip J. , Dai David , Smith Eric E. , Schwamm Lee H. , Bhatt Deepak L. , Xian Ying , Saver Jeffrey L. , Reeves Mathew J. , Peterson Eric D. , Hernandez Adrian F.
Published: October 2015

Background—

Patients with transient ischemic attack (TIA) are at increased risk for ischemic stroke. We derived a prediction rule for 1-year ischemic stroke risk post-TIA, examining estimated risk, receipt of inpatient quality of care measures for TIA, and the presence or absence of stroke at 1 year post discharge.

Methods and Results—

We linked 67 892 TIA Get With The Guidelines-Stroke patients >65 years (2003–2008) to Medicare inpatient claims to obtain longitudinal outcomes. Using Cox proportional hazards modeling in a split sample, we identified baseline demographics and clinical characteristics associated with ischemic stroke admission during the year post-TIA, and developed a Get With The Guidelines Ischemic Stroke after TIA Risk Score; performance was examined in the validation sample. Quality of care was estimated by a global defect-free care measure, and individual performance measures within estimated risk score quintiles. The overall hospital admission rate for ischemic stroke during the year post-TIA was 5.7%. Patients with ischemic stroke were more likely to be older, black, and have higher rates of smoking, previous stroke, diabetes mellitus, previous myocardial infarction, heart failure, and atrial fibrillation. The Risk Score showed moderate discriminative performance (c-statistic=0.606); highest quintile patients were less likely to receive statins, smoking cessation counseling, and defect-free care. Although not associated with 1-year ischemic stroke, DCF was associated with a significantly lower risk of all-cause mortality.

Conclusions—

TIA patients with high estimated ischemic stroke risk are less likely to receive defect-free care than low-risk patients. Standardized risk assessment and delivery of optimal inpatient care are needed to reduce this risk-treatment mismatch.
Mobile Phone–Based Questionnaire for Assessing 3 Months Modified Rankin Score After Acute Stroke
Authors: Cooray Charith , Matusevicius Marius , Wahlgren Nils , Ahmed Niaz
Published: October 2015

Background—

In many countries, a majority of stroke patients are not assessed for long-term functional outcome owing to limited resources and time. We investigated whether automatic assessment of the modified Rankin Scale (mRS) based on a mobile phone questionnaire may serve as an alternative to mRS assessments at clinical visits after stroke.

Methods and Results—

We enrolled 62 acute stroke patients admitted to our stroke unit during March to May 2014. Forty-eight patients completed the study. During the stay, patients and/or caregivers were equipped with a mobile phone application in their personal mobile phones. The mobile phone application contained a set of 20 questions, based on the Rankin Focused Assessment, which we previously tested in a pilot study. Three months after inclusion, the mobile phone application automatically prompted the study participants to answer the mRS questionnaire in the mobile phones. Each question or a group of questions in the questionnaire corresponded to a certain mRS score. Using a predefined protocol, the highest mRS score question where the study participant had answered yes was deemed the final mobile mRS score. A few days later, a study personnel performed a clinical visit mRS assessment. The 2 assessments were compared using quadratic weighing κ-statistics. Mean age was 67 years (38% females), and median baseline National Institutes of Health Stroke Scale (NIHSS) score was 5 (interquartile range 2–10.5, range 0–23). Median and mean clinical visit mRS at 3 months was 2 and 2.3, respectively. We found a 62.5% agreement between clinical visit and mobile mRS assessment, weighted kappa 0.89 (95% confidence interval 0.82–0.96), and unweighted kappa 0.53 (95% confidence interval 0.36–0.70). Dichotomized mRS outcome separating functionally independent (mRS score 0–2) from dependent (mRS score 3–5) showed 83% agreement and unweighted kappa of 0.66 (95% confidence interval 0.45–0.87).

Conclusions—

Mobile phone–based automatic assessments of mRS performed well in comparison with clinical visit mRS and could be used as an alternative in stroke follow-up.
Changes in European Label and Guideline Adherence After Updated Recommendations for Stroke Thrombolysis
Authors: Anani Nadim , Mazya Michael V. , Bill Olivier , Chen Rong , Koch Sabine , Ahmed Niaz , Wahlgren Nils , Prazeres Moreira Tiago
Published: October 2015

Background—

Intravenous thrombolysis (IVT) for acute ischemic stroke is subject to label and guideline contraindications. Updated European guidelines in 2008/2009 recommended IVT in selected patients aged >80 years and stroke onset-to-treatment time 3 to 4.5 hours, which the label still prohibited. Our aim was to compare contraindication nonadherence before and after the guideline update.

Methods and Results—

Data on IVT-treated patients with stroke at 232 European hospitals participating in the Safe Implementation of Treatments in Stroke registry during both periods 2006 to 2007 (n=6354) and 2010 to 2011 (n=12 046). After the 2008/2009 guideline update, the proportion of patients nonadherent to label increased from 23.6% to 51.1% (
P
<0.001). Specifically, nonadherence to onset-to-treatment time >3 hours increased from 8.2% to 27.9% and IVT in patients aged >80 years from 8.9% to 17.2% (both
P
<0.001). Nonadherence also increased to the contraindications severe stroke (National Institutes of Health Stroke Scale score >25), onset-to-treatment time >4.5 hours, blood pressure >185/110 mm Hg, and ongoing oral anticoagulation (all
P
≤0.001). Higher hospital IVT patient volumes were associated with higher nonadherence rates.

Conclusions—

After the European guideline update, new recommendations were promptly adopted and nonadherence to the unchanged label increased. Label contraindications should be updated.
Chronic Stroke Outcome Measures for Motor Function Intervention Trials
Authors: Bushnell Cheryl , Bettger Janet Prvu , Cockroft Kevin M. , Cramer Steven C. , Edelen Maria Orlando , Hanley Daniel , Katzan Irene L. , Mattke Soeren , Nilsen Dawn M. , Piquado Tepring , Skidmore Elizabeth R. , Wing Kay , Yenokyan Gayane
Published: October 2015

Background—

About half of survivors with stroke experience severe and significant long-term disability. The purpose of this article is to review the state of the science and to make recommendations for measuring patient-centric outcomes in interventions for motor improvement in the chronic stroke phase.

Methods and Results—

A 9-member expert panel reviewed evidence to identify measures of upper and lower extremity function used to date as outcomes in trials with patients who experienced a stroke ≥6 months before assessment. Outcome measures were screened using StrokEDGE consensus panel recommendations, and evaluated for availability of a published minimal clinically important difference. Measures meeting these criteria were further evaluated with regard to their level of measurement, psychometric properties, and ability of minimal clinically important difference to capture gains associated with improved function and clinical relevance to patients, to arrive at recommendations. A systematic literature review yielded 115 clinical trials of upper and lower extremity function in chronic stroke that used a total of 34 outcome measures. Seven of these had published minimal clinically important differences and were recommended or highly recommended by StrokEDGE. Those are the Fugl-Meyer Upper Extremity and Lower Extremity scales, Wolf Motor Function Test, Action Research Arm Test, Ten-Meter and Six-Minute Walk Tests, and the Stroke Impact Scale. All had evidence for their psychometric performance, although the strength of evidence for validity varied, especially in populations with chronic stroke Fugl-Meyer Upper and Lower Extremity scales showing the strongest evidence for validity.

Conclusions—

The panel recommends that the Fugl-Meyer Upper and Lower Extremity scales be used as primary outcomes in intervention trials targeting motor function in populations with chronic stroke. The other 6 measures are recommended as secondary outcomes.
Restoration of Pulsatile Flow Reduces Sympathetic Nerve Activity Among Individuals With Continuous-Flow Left Ventricular Assist Devices
Authors: Cornwell William K. , Tarumi Takashi , Stickford Abigail , Lawley Justin , Roberts Monique , Parker Rosemary , Fitzsimmons Catherine , Kibe Julius , Ayers Colby , Markham David , Drazner Mark H. , Fu Qi , Levine Benjamin D.
Published: October 2015

Background—

Current-generation left ventricular assist devices provide circulatory support that is minimally or entirely nonpulsatile and are associated with marked increases in muscle sympathetic nerve activity (MSNA), likely through a baroreceptor-mediated pathway. We sought to determine whether the restoration of pulsatile flow through modulations in pump speed would reduce MSNA through the arterial baroreceptor reflex.

Methods and Results—

Ten men and 3 women (54±14 years) with Heartmate II continuous-flow left ventricular assist devices underwent hemodynamic and sympathetic neural assessment. Beat-to-beat blood pressure, carotid ultrasonography at the level of the arterial baroreceptors, and MSNA via microneurography were continuously recorded to determine steady-state responses to step changes (200–400 revolutions per minute) in continuous-flow left ventricular assist device pump speed from a maximum of 10 480±315 revolutions per minute to a minimum of 8500±380 revolutions per minute. Reductions in pump speed led to increases in pulse pressure (high versus low speed: 17±7 versus 26±12 mm Hg;
P
<0.01), distension of the carotid artery, and carotid arterial wall tension (
P
<0.05 for all measures). In addition, MSNA was reduced (high versus low speed: 41±15 versus 33±16 bursts per minute;
P
<0.01) despite a reduction in mean arterial pressure and was inversely related to pulse pressure (
P
=0.037).

Conclusions—

Among subjects with continuous-flow left ventricular assist devices, the restoration of pulsatile flow through modulations in pump speed leads to increased distortion of the arterial baroreceptors with a subsequent decline in MSNA. Additional study is needed to determine whether reduction of MSNA in this setting leads to improved outcomes.
Finding Protoevangelical Faith: A Summary of Four Ethnographic Studies
Authors: Black Gary
Published: October 2015

This article presents a summary of the findings from four ethnographic studies of postevangelical groups interpreting and applying the theology and praxis of Dr. Dallas Willard. Willard’s works have become increasingly attractive to emerging generations of so called “postevangelical” Christians protesting the perceived excesses and hegemony of mainstream evangelical religion in the United States. Willardian theology is seen as providing a positive alternative to contemporary versions of evangelicalism. For increasing numbers of disaffected evangelicals with postmodern sensibilities, Willard’s “protoevangelical” vision offers a more robust doctrine of God, a return to the primacy of discipleship to Christ, and the experience of a holistic and integrated life in the Kingdom of God.
The Focus Group Method in Practical Ecclesiology: Performative Effects and Ecclesiological Rationale
Authors: de Roest Henk
Published: October 2015

The author gives an analysis of the methodological advantages and disadvantages of using focus groups in practical ecclesiology. He makes a plea for including focus groups in a mixed method strategy in practical ecclesiological research, being attentive to their performative effects. He asks, if ecclesiology governs the methodological design of a practical-ecclesiological research project, should not methods that focus on conversational practices and how people build up a view out of the interaction that takes place within a group, be pulled into the heart of the research? In his reply to this question, the article gives a relational-constructionist, an ecclesiological and a theological rationale for using focus groups.
A new species of freshwater sponge, Heteromeyenia barlettai sp. nov. from an aquarium in São Paulo, Brazil (Spongillida: Spongillidae)
Authors: PINHEIRO ULISSES , CALHEIRA LUDIMILA , HAJDU EDUARDO
Published: October 2015

A new species of freshwater sponge, Heteromeyenia barlettai sp. nov., is proposed here based on specimens discovered in a private aquarium in São Paulo, Brazil, and most likely inadvertently collected from the Paraná Basin. The present study also presents a redescription of H. insignis on the basis of the specimen reported upon by Volkmer (1963), collected from the Atlântico Sul Hydrographic Basin. Spicule measurements (n=30) were made for comparison with other              Heteromeyenia species. This is the first time that H. insignis has its complete set of spicules studied under SEM. After comparison with the redescription of the type of H. baileyi, we also find characteristics that justify the maintenance of H. insignis as a valid species. A key to species of Heteromeyenia is provided.
A new species and two new combinations in the genus Strotihypera Kononenko & Han, 2011 (Lepidoptera, Noctuidae, Noctuinae: Elaphriini). A postscript to the description of the genus Strotihypera
Authors: HAN H. L. , KONONENKO V. S.
Published: October 2015

Elaphriini is a small tribe of the subfamily Noctuinae with predominantly New World distribution. Only three genera, Elaphria Hübner, 1818 with four species, Galgula Guenée, 1852 with one species (Fibiger & Hacker 2010) and Strotihypera Kononenko & Han, 2011 with one species are known from the Eurasia. The majority of species occurs in tropical and subtropical regions. The review of Eurasian Elaphriini with description of the new genus Strotihypera has recently been published by Kononenko & Han (2011). In the subsequent years in the result of intensive collecting in South West China we found a new species allied to Strotihypera flavipuncta (Leech, 1889) and two related species Strotihypera ochreipuncta (Wileman, 1914), comb. n. and “Hyperstrotia” macroplaga (Hampson, 1907), comb. n. The description of a new species and the review of two of its allies are presented here as a postscript to the description of the genus Strotihypera (Kononenko & Han 2011).
Uca (Petruca), a new subgenus for the rock fiddler crab Uca panamensis
(Stimpson, 1859) from Central America, with comments on some species of the American broad-fronted subgenera
Authors: Shih Hsi-Te , Ng Peter K. L. , Christy John H.
Published: October 2015

Among the fiddler crabs from the Americas, Uca panamensis (Stimpson, 1859) (Crustacea: Decapoda: Ocypodidae) is unusual in its behavior and ecology, living in stony habitats rather than sandy or muddy substrates. This species also has several unusual morphological characters of the carapace and major and minor chelae, and had been placed in either the subgenera Minuca Bott, 1954, or Leptuca Bott, 1973. The armature at the inner corner of the orbital floor, as well as the morphology of the urocardiac ossicles of the gastric mill of U. panamensis, are, however, plesiomorphic characters, and are closer to the condition in species belonging the subgenera Uca and Afruca. Phylogenetic relationships, based on mitochondrial 16S rDNA and cytochrome oxidase subunit I, and nuclear 28S rDNA, supported by its unusual morphological features indicate that this species belongs to its own subgenus. A new subgenus Uca (Petruca) subgen. nov. is herein established for U. panamensis. In addition, the status of Uca thayeri Rathbun, 1900, U. umbratila Crane, 1941, U. virens Salmon & Atsaides, 1968, and U. longisignalis Salmon & Atsaides, 1968, are revised and discussed based on a reappraisal of their phylogenetic relationships.
Taxonomic notes on the crab spider genus Tobias Simon, 1895 (Araneae, Thomisidae, Stephanopinae)
Authors: MACHADO MIGUEL , TEIXEIRA RENATO AUGUSTO , LISE ARNO ANTONIO
Published: October 2015

The males of Tobias caudatus Mello-Leitão, 1929 and Tobias pustulosus Simon, 1929 are described for the first time, females are redescribed and both sexes are illustrated. New distribution records are presented for both species. Tobias monstruosus Mello-Leitão, 1929 is considered a junior synonym of T. pustulosus. The types of Tobias albovittatus Caporiacco, 1954, and Tobias gradiens Mello-Leitão, 1929 are lost, and Tobias albicans Mello-Leitão, 1929 and Tobias corticatus Mello-Leitão, 1917 are known only from poorly preserved specimens, thus they all are considered nomina dubia.
Advancements in Objective Multisatellite Tropical Cyclone Center Fixing
Authors: Wimmers Anthony J. , Velden Christopher S.
Published: October 2015

An improved version of the Automated Rotational Center Hurricane Eye Retrieval (ARCHER) tropical cyclone (TC) center-fixing algorithm, introduced here as “ARCHER-2,” is presented with a characterization of its accuracy and precision and a comparison with alternative methods. The algorithm is calibrated for 37- and 85–92-GHz microwave imagers; geostationary imagery at visible, near-infrared, and longwave infrared window channels; and scatterometer ambiguities. In addition to a center fix, ARCHER-2 produces a quantitative estimate of expected error that can be used automatically or manually to evaluate the suitability of a result. The median center-fix error ranges from 24 (using scatterometer) to 49 (using infrared window) km relative to the National Hurricane Center best track. Multisatellite, multisensor results can also be used together to produce a TC-track estimate that selects from the best of all of the available imagery in the ancillary “ARCHER-Track” product. The median error of ARCHER-Track varies between 17 and 38 km, depending on TC intensity and data latency. The bias of the product’s expected error varies between 0% and 12%, which translates to an average of only 4 km. When compared with operational, subjective center-fix estimates, the ARCHER-Track approach improves on 29%–43% of these cases at the tropical-depression and tropical-storm stages, at which further assistance is typically sought. This result demonstrates that ARCHER-2 and ARCHER-Track can complement and accelerate operational forecasting where needed and can furnish other automated TC-analysis methods with well-characterized center-fix information.
Estimates of Air–Sea Feedbacks on Sea Surface Temperature Anomalies in the Southern Ocean
Authors: Hausmann Ute , Czaja Arnaud , Marshall John
Published: October 2015

Sea surface temperature (SST) air–sea feedback strengths and associated decay time scales in the Southern Ocean (SO) are estimated from observations and reanalysis datasets of SST, air–sea heat fluxes, and ocean mixed layer depths. The spatial, seasonal, and scale dependence of the air–sea heat flux feedbacks is mapped in circumpolar bands and implications for SST persistence times are explored. It is found that the damping effect of turbulent heat fluxes dominates over that due to radiative heat fluxes. The turbulent heat flux feedback acts to damp SSTs in all bands and spatial scales and in all seasons, at rates varying between 5 and 25 W m−2 K−1, while the radiative heat flux feedback has a more uniform spatial distribution with a magnitude rarely exceeding 5 W m−2 K−1. In particular, the implied net air–sea feedback (turbulent + radiative) on SST south of the polar front, and in the region of seasonal sea ice, is as weak as 5–10 W m−2 K−1 in the summertime on large spatial scales. Air–sea interaction alone thus allows SST signals induced around Antarctica in the summertime to persist for several seasons. The damping effect of mixed layer entrainment on SST anomalies averages to approximately 20 W m−2 K−1 across the ACC bands in the summer-to-winter entraining season and thereby reduces summertime SST persistence to less than half of that predicted by air–sea interaction alone (i.e., 3–6 months).
Understanding the Rapid Precipitation Response to CO2 and Aerosol Forcing on a Regional Scale*
Authors: Richardson Thomas B. , Forster Piers M. , Andrews Timothy , Parker Doug J.
Published: October 2015

Precipitation exhibits a significant rapid adjustment in response to forcing, which is important for understanding long-term climate change. In this study, fixed sea surface temperature (SST) simulations are used to analyze the spatial pattern of the rapid precipitation response. Three different forcing scenarios are investigated using data obtained from phase 5 of CMIP (CMIP5): an abrupt quadrupling of CO2, an abrupt increase in sulfate, and an abrupt increase in all anthropogenic aerosol levels from preindustrial to present day. Analysis of the local energy budget is used to understand the mechanisms that drive the observed changes.

It is found that the spatial pattern of the rapid precipitation response to forcing is primarily driven by rapid land surface temperature change, rather than the change in tropospheric diabatic cooling. As a result, the pattern of response due to increased CO2 opposes that due to sulfate and all anthropogenic aerosols, because of the opposing surface forcing. The rapid regional precipitation response to increased CO2 is robust among models, implying that the uncertainty in long-term changes is mainly associated with the response to SST-mediated feedbacks. Increased CO2 causes rapid warming of the land surface, which destabilizes the troposphere, enhancing convection and precipitation over land in the tropics. Precipitation is reduced over most tropical oceans because of a weakening of overturning circulation and a general shift of convection to over land. Over most land regions in the midlatitudes, circulation changes are small. Reduced tropospheric cooling therefore leads to drying over many midlatitude land regions.
Uncertainty in Model Climate Sensitivity Traced to Representations of Cumulus Precipitation Microphysics
Authors: Zhao Ming , Golaz J.-C. , Held I. M. , Ramaswamy V. , Lin S.-J. , Ming Y. , Ginoux P. , Wyman B. , Donner L. J. , Paynter D. , Guo H.
Published: October 2015

Uncertainty in equilibrium climate sensitivity impedes accurate climate projections. While the intermodel spread is known to arise primarily from differences in cloud feedback, the exact processes responsible for the spread remain unclear. To help identify some key sources of uncertainty, the authors use a developmental version of the next-generation Geophysical Fluid Dynamics Laboratory global climate model (GCM) to construct a tightly controlled set of GCMs where only the formulation of convective precipitation is changed. The different models provide simulation of present-day climatology of comparable quality compared to the model ensemble from phase 5 of CMIP (CMIP5). The authors demonstrate that model estimates of climate sensitivity can be strongly affected by the manner through which cumulus cloud condensate is converted into precipitation in a model’s convection parameterization, processes that are only crudely accounted for in GCMs. In particular, two commonly used methods for converting cumulus condensate into precipitation can lead to drastically different climate sensitivity, as estimated here with an atmosphere–land model by increasing sea surface temperatures uniformly and examining the response in the top-of-atmosphere energy balance. The effect can be quantified through a bulk convective detrainment efficiency, which measures the ability of cumulus convection to generate condensate per unit precipitation. The model differences, dominated by shortwave feedbacks, come from broad regimes ranging from large-scale ascent to subsidence regions. Given current uncertainties in representing convective precipitation microphysics and the current inability to find a clear observational constraint that favors one version of the authors’ model over the others, the implications of this ability to engineer climate sensitivity need to be considered when estimating the uncertainty in climate projections.
Quantifying the Sources of Intermodel Spread in Equilibrium Climate Sensitivity
Authors: Caldwell Peter M. , Zelinka Mark D. , Taylor Karl E. , Marvel Kate
Published: October 2015

This study clarifies the causes of intermodel differences in the global-average temperature response to doubled CO2, commonly known as equilibrium climate sensitivity (ECS). The authors begin by noting several issues with the standard approach for decomposing ECS into a sum of forcing and feedback terms. This leads to a derivation of an alternative method based on linearizing the effect of the net feedback. Consistent with previous studies, the new method identifies shortwave cloud feedback as the dominant source of intermodel spread in ECS. This new approach also reveals that covariances between cloud feedback and forcing, between lapse rate and longwave cloud feedbacks, and between albedo and shortwave cloud feedbacks play an important and previously underappreciated role in determining model differences in ECS. Defining feedbacks based on fixed relative rather than specific humidity (as suggested by Held and Shell) reduces the covariances between processes and leads to more straightforward interpretations of results.