bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Differences in Treatment Impact Racial and Ethnic Disparities in Acute Myeloid Leukemia?
Authors: Patel Manali I. , Ma Yifei , Mitchell Beverly , Rhoads Kim F.
Published: February 2015

Background: We previously demonstrated disparate acute myelogenous leukemia (AML) survival for black and Hispanic patients; these differences persisted despite younger ages and higher prevalence of favorable cytogenetics in these groups. This study determined: (i) whether there are differences in treatment delivered to minorities, and (ii) how these differences affect outcomes in AML. We hypothesize that differences in treatment explain some proportion of survival disparities.

Methods: We used California Cancer Registry data linked to hospital discharge abstracts for patients with AML (1998–2008). Logistic regression models estimated odds of treatment (chemotherapy and/or hematopoietic stem cell transplant) by race/ethnicity. Cox proportional hazard models estimated mortality by race after adjustment for treatment.

Results: We analyzed 11,084 records. Black race was associated with lower odds of chemotherapy [OR, 0.74; 95% confidence interval (CI), 0.61–0.91]. Black and Hispanic patients had decreased odds of transplant [(OR, 0.64; 95% CI, 0.46–0.87); (OR, 0.74; 95% CI, 0.62–0.89), respectively]. Black patients had increased hazard of mortality (HR, 1.14; 95% CI, 1.04–1.25) compared with whites. Adjustment for receipt of any treatment resulted in decreased mortality (HR, 1.09; 95% CI, 1.00–1.20) for black patients.

Conclusions: AML treatment differences for black patients explain some proportion of the disparity. Future AML disparities studies should investigate socioeconomic and other characteristics.

Impact: Study findings may better elucidate drivers of disparities in AML. Cancer Epidemiol Biomarkers Prev; 24(2); 344–9. ©2015 AACR.
Multifunctional Polymeric Micelles Co-loaded with Anti–Survivin siRNA and Paclitaxel Overcome Drug Resistance in an Animal Model of Ovarian Cancer
Authors: Salzano Giuseppina , Navarro Gemma , Trivedi Malav S. , De Rosa Giuseppe , Torchilin Vladimir P.
Published: February 2015

Ovarian cancer is a dreadful disease estimated to be the second most common gynecologic malignancy worldwide. Its current therapy, based on cytoreductive surgery followed by the combination of platinum and taxanes, is frequently complicated by the onset of multidrug resistance (MDR). The discovery that survivin, a small antiapoptotic protein, is involved in chemoresistance provided a new prospect to overcome MDR in cancer, because siRNA could be used to inhibit the expression of survivin in cancer cells. With this in mind, we have developed self-assembly polymeric micelles (PM) able to efficiently co-load an anti–survivin siRNA and a chemotherapeutic agent, such as paclitaxel (PXL; survivin siRNA/PXL PM). Previously, we have successfully demonstrated that the downregulation of survivin by using siRNA-containing PM strongly sensitizes different cancer cells to paclitaxel. Here, we have evaluated the applicability of the developed multifunctional PM in vivo. Changes in survivin expression, therapeutic efficacy, and biologic effects of the nanopreparation were investigated in an animal model of paclitaxel-resistant ovarian cancer. The results obtained in mice xenografed with SKOV3-tr revealed a significant downregulation of survivin expression in tumor tissues together with a potent anticancer activity of survivin siRNA/PXL PM, while the tumors remained unaffected with the same quantity of free paclitaxel. These promising results introduce a novel type of nontoxic and easy-to-obtain nanodevice for the combined therapy of siRNA and anticancer agents in the treatment of chemoresistant tumors. Mol Cancer Ther; 14(4); 1075–84. ©2015 AACR.
Targeting Integrin-Linked Kinase Suppresses Invasion and Metastasis through Downregulation of Epithelial-to-Mesenchymal Transition in Renal Cell Carcinoma
Authors: Han Kyung Seok , Li Na , Raven Peter A. , Fazli Ladan , Ettinger Susan , Hong Sung Joon , Gleave Martin E. , So Alan I.
Published: February 2015

Renal cell carcinoma (RCC) is the most common malignancy in the kidney. Antiangiogenic targeted therapies inhibit the progression of RCC, but have limited impacts on invasion or metastasis of tumor cells. Integrin-linked kinase (ILK) is a serine/threonine kinase implicated in the regulation of cell growth/survival, cell-cycle progression, epithelial–mesenchymal transition (EMT), invasion/migration, and angiogenesis. However, the role of ILK in RCC has not been evaluated. We investigated the role of ILK on cancer progression and metastasis and the therapeutic potential of ILK inhibition in RCC. Our investigation reveals that ILK is expressed at a low level in normal cells and low-stage RCC cells and is highly expressed in advanced and metastatic cells. Caki-1, a metastatic RCC cell line, showed higher expression of molecular EMT markers, including Snail and Zeb1, but decreased activity of GSK3β. Knockdown of ILK using small interference (si)-ILK minimally inhibited tumor proliferation and cell-cycle progression was not significantly affected. However, ILK knockdown suppressed the formation of stress fibers and focal adhesions and impeded phenotypic EMT markers, including cell migration and invasion, in Caki-1 and UMRC-3 cells. Finally, in vivo knockdown of ILK suppressed the progression, invasion, and metastasis of primary RCC in nude mice by downregulation of EMT markers (Snail, Zeb1, vimentin, and E-cadherin). Our results show that ILK may be essential for invasion and metastasis in RCC and regulates vimentin and E-cadherin expression by regulating the EMT-related transcription factors Snail and Zeb1. These results suggest that ILK may be a potential target in RCC. Mol Cancer Ther; 14(4); 1024–34. ©2015 AACR.
Magnetic Resonance Spectroscopy for Detection of Choline Kinase Inhibition in the Treatment of Brain Tumors
Authors: Kumar Manoj , Arlauckas Sean P. , Saksena Sona , Verma Gaurav , Ittyerah Ranjit , Pickup Stephen , Popov Anatoliy V. , Delikatny Edward J. , Poptani Harish
Published: February 2015

Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both preclinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines. In vivo MRS studies of rats with intracranial F98-derived brain tumors showed a significant decrease in tumor total choline concentration after treatment with MN58b. High-resolution MRS of tissue extracts confirmed that this decrease was due to a significant reduction in phosphocholine. Concomitantly, a significant increase in poly-unsaturated lipid resonances was also observed in treated tumors, indicating apoptotic cell death. MRI-based volume measurements demonstrated a significant growth arrest in the MN58b-treated tumors in comparison with saline-treated controls. Histologically, MN58b-treated tumors showed decreased cell density, as well as increased apoptotic cells. These results suggest that inhibition of choline kinase can be used as an adjuvant to chemotherapy in the treatment of brain tumors and that decreases in total choline observed by MRS can be used as an effective pharmacodynamic biomarker of treatment response. Mol Cancer Ther; 14(4); 899–908. ©2015 AACR.
Microbiota Modulation of Myeloid Cells in Cancer Therapy
Authors: Goldszmid Romina S. , Dzutsev Amiran , Viaud Sophie , Zitvogel Laurence , Restifo Nicholas P. , Trinchieri Giorgio
Published: February 2015

Myeloid cells represent a major component of the tumor microenvironment, where they play divergent dual roles. They can induce antitumor immune responses, but mostly they promote immune evasion, tumor progression, and metastasis formation. Thus, strategies aiming at reprogramming the tumor microenvironment represent a promising immunotherapy approach. Myeloid cells respond to environmental factors including signals derived from commensal microbes. In this Cancer Immunology at the Crossroads overview, we discuss recent advances on the effects of the commensal microbiota on myeloid-cell functions and how they affect the response to cancer therapy. Cancer Immunol Res; 3(2); 103–9. ©2015 AACR.
P-Selectin Inhibition Therapeutically Promotes Thrombus Resolution and Prevents Vein Wall Fibrosis Better Than Enoxaparin and an Inhibitor to von Willebrand Factor
Authors: Diaz Jose A. , Wrobleski Shirley K. , Alvarado Christine M. , Hawley Angela E. , Doornbos Nichole K. , Lester Patrick A. , Lowe Suzan E. , Gabriel Joy E. , Roelofs Karen J. , Henke Peter K. , Schaub Robert G. , Wakefield Thomas W. , Myers Daniel D.
Published: February 2015

Objective—

Aptamers are oligonucleotides targeting protein–protein interactions with pharmacokinetic profiles and activity reversal options. Although P-selectin and von Willebrand factor (vWF) have been implicated in the development of venous thrombosis (VT), no studies have directly compared aptamer efficacy with standard of care in VT. In this study, ARC5692, an anti-P-selectin aptamer, and ARC15105, an anti-vWF aptamer, were compared with low–molecular-weight heparin, enoxaparin, to test the efficacy of P-selectin or vWF inhibition in promoting thrombus resolution and preventing vein wall fibrosis, in a baboon model of VT.

Approach and Results—

Groups were as follows: treatment arm: animals received P-selectin or vWF aptamer inhibitors or enoxaparin (n=3 per group). Controls received no treatment (n=3). Prophylactic arm: animals received P-selectin inhibitor (n=4) or vWF inhibitor (n=3). Treatment arm: P-selectin-inhibitor demonstrated a significant improvement in vein recanalization by magnetic resonance venography (73% at day 21), and significantly decreased vein wall collagen, compared with all groups. Anti–P-selectin equaled enoxaparin in maintaining valve competency by ultrasound. All control animals had compromised valve competency post thrombosis. Prophylactic arm: animals receiving P-selectin and vWF inhibitors demonstrated improved vein recanalization by magnetic resonance venography versus controls (80% and 85%, respectively, at day 21). Anti–P-selectin protected iliac valve function better than anti-vWF, and both improved valve function versus controls. No adverse bleeding events were observed.

Conclusions—

The P-selectin inhibitor aptamer promoted iliac vein recanalization, preserved valve competency, and decreased vein wall fibrosis. The results of this work suggest that P-selectin inhibition maybe an ideal target in the treatment and prophylaxis of deep VT, warranting clinical trials.
Sleep Apnea Is Independently Associated With Peripheral Arterial Disease in the Hispanic Community Health Study/Study of Latinos
Authors: Shah Neomi , Allison Matthew , Teng Yanping , Wassertheil-Smoller Sylvia , Sotres-Alvarez Daniela , Ramos Alberto R. , Zee Phyllis C. , Criqui Michael H. , Yaggi Henry K. , Gallo Linda C. , Redline Susan , Kaplan Robert C.
Published: February 2015

Objective—

Sleep apnea (SA) has been linked with various forms of cardiovascular disease, but little is known about its association with peripheral artery disease (PAD) measured using the ankle–brachial index. This relationship was evaluated in the Hispanic Community Health Study/Study of Latinos.

Approach and Results—

We studied 8367 Hispanic Community Health Study/Study of Latinos participants who were 45 to 74 years of age. Sleep symptoms were examined with the self-reported Sleep Health Questionnaire. SA was assessed using an in-home sleep study. Systolic blood pressure was measured in all extremities to compute the ankle–brachial index. PAD was defined as ankle–brachial index <0.90 in either leg. Multivariable logistic regression was used to investigate the association between moderate-to-severe SA, defined as apnea–hypopnea index ≥15, and the presence of PAD. Analyses were adjusted for covariates. The prevalence of PAD was 4.7% (n=390). The mean apnea–hypopnea index was significantly higher among adults with PAD compared with those without (11.1 versus 8.6 events/h;
P
=0.046). After adjusting for covariates, moderate-to-severe SA was associated with a 70% increase in the odds of PAD (odds ratio, 1.7; 95% confidence interval, 1.1–2.5;
P
=0.0152). This association was not modified by sex (
P
=0.8739). However, there was evidence that the association between moderate-to-severe SA and PAD varied by Hispanic/Latino background (
P
<0.01). Specifically, the odds were stronger in Mexican (adjusted odds ratio, 2.9; 95% confidence interval, 1.3–6.2) and in Puerto Rican Americans (adjusted odds ratio, 2.0; 95% confidence interval, 0.97–4.2) than in other backgrounds.

Conclusions—

Moderate-to-severe SA is associated with higher odds of PAD in Hispanic/Latino adults.
Sex Differences in Platelet Toll-Like Receptors and Their Association With Cardiovascular Risk Factors
Authors: Koupenova Milka , Mick Eric , Mikhalev Ekaterina , Benjamin Emelia J. , Tanriverdi Kahraman , Freedman Jane E.
Published: February 2015

Objective—

Platelets contribute to thrombosis, and platelet toll-like receptors (TLRs) are central in pathogen detection, potentially mediating infection-induced vascular occlusion. Using a large community-based cohort study, we sought to examine if platelets express all known TLR transcripts and analyze their association with cardiovascular risk factors.

Approach and Results—

mRNA levels for TLRs were measured in isolated platelets by high-throughput quantitative reverse transcriptase polymerase chain reaction in 1625 participants (mean age, 66.6±9; 54% women) of the Framingham Heart Study. We measured circulating inflammatory and thrombotic markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein 1, intracellular cell adhesion molecule 1, soluble tumor necrosis factor-α receptor 1, and soluble p-selectin) and analyzed TLRs and their association with sex and cardiovascular risk factors by multivariable logit regression model adjusted for confounding factors. Platelets expressed all 10 TLR transcripts, and all TLRs were coexpressed. Women had higher platelet TLR expression, which associated with different cardiovascular risk factors, compared with men. In women, TLR1, TLR3, TLR6, and TLR7 were associated with body mass index and TLR5, TLR7, and TLR10 were associated with total cholesterol to high-density lipoprotein ratio. In men, TLR1, TLR2, and TLR3 were associated with lipid and TLR8 with hypertension treatment. Similarly, TLR expression in men was more commonly associated with circulating inflammatory markers (soluble tumor necrosis factor-α receptor 1 and intracellular cell adhesion molecule 1), whereas in women, TLR expression was associated with soluble p-selectin levels.

Conclusions—

We report the first study to demonstrate that platelets express all TLR transcripts using a large community-based observational cohort. These transcripts are more abundant in women and have distinct associations with cardiovascular risk and inflammatory biomarkers that vary by sex.
Noninvasive Molecular Imaging of Apoptosis in a Mouse Model of Anthracycline-Induced Cardiotoxicity
Authors: Su Helen , Gorodny Natalia , Gomez Luis Felipe , Gangadharmath Umesh , Mu Fanrong , Chen Gang , Walsh Joseph C. , Szardenings Katrin , Kolb Hartmuth C. , Tamarappoo Balaji
Published: February 2015

Background—

Anthracycline-induced cardiotoxicity and myocardial dysfunction may be associated with apoptosis. Caspase 3 catalyzes a terminal step in apoptosis, and its expression may serve as a marker of cardiomyocyte apoptosis. We synthesized 18F-CP18, a caspase-3 substrate and evaluated cardiac 18F-CP18 uptake in a mouse model of anthracycline cardiotoxicity.

Methods and Results—

For 12 weeks, mice were injected with doxorubicin, 3 mg/kg/week, or vehicle (control). Left ventricular fractional shortening was quantified by echocardiography. CP18 uptake after intravenous injection of 250 μCi of 18F-CP18, 24 hours post-doxorubicin treatment was quantified by microPET, autoradiography, and gamma counting. Apoptosis was assessed by enzymatic assay of myocardial caspase 3 and TUNEL staining of tissue sections. Compared with controls, at 6 and 12 weeks of doxorubicin treatment, fractional shortening was reduced (20.7%±2.5% versus 31%±3.5%,
P
=0.010; and 20.3%±3.1% versus 32.4%±2.1%,
P
=0.011). Doxorubicin treatment was associated with increased 18F-CP18 uptake in %ID/g by gamma counting from 0.36±0.01 (week 1) to 0.78±0.01 (week 12),
P
=0.003. A similar increase in 18F-CP18 uptake was observed by microPET (0.41±0.04 versus 0.73±0.1,
P
=0.014) and autoradiography (1.1±0.3 versus 2.8±0.2
P
=0.001). Caspase 3 enzymatic activity and apoptosis by TUNEL staining were also increased after 12 weeks of doxorubicin compared with weeks 1 and 3. CP18 uptake in controls was relatively unchanged at weeks 1, 3, and 12.

Conclusions—

In a mouse model of cardiotoxicity, doxorubicin treatment is associated with increased myocardial caspase 3 expression and an increase in CP18 uptake. 18F-CP18 may be useful for detection of anthracycline-induced myocardial apoptosis.
Impact of Mitral Regurgitation on Clinical Outcomes of Patients With Low-Ejection Fraction, Low-Gradient Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation
Authors: O’Sullivan Crochan J. , Stortecky Stefan , Bütikofer Anne , Heg Dik , Zanchin Thomas , Huber Christoph , Pilgrim Thomas , Praz Fabien , Buellesfeld Lutz , Khattab Ahmed A. , Blöchlinger Stefan , Carrel Thierry , Meier Bernhard , Zbinden Stephan , Wenaweser Peter , Windecker Stephan
Published: February 2015

Background—

Up to 1 in 6 patients undergoing transcatheter aortic valve implantation (TAVI) present with low-ejection fraction, low-gradient (LEF-LG) severe aortic stenosis and concomitant relevant mitral regurgitation (MR) is present in 30% to 55% of these patients. The effect of MR on clinical outcomes of LEF-LG patients undergoing TAVI is unknown.

Methods and Results—

Of 606 consecutive patients undergoing TAVI, 113 (18.7%) patients with LEF-LG severe aortic stenosis (mean gradient ≤40 mm Hg, aortic valve area <1.0 cm
2
, left ventricular ejection fraction <50%) were analyzed. LEF-LG patients were dichotomized into ≤mild MR (n=52) and ≥moderate MR (n=61). Primary end point was all-cause mortality at 1 year. No differences in mortality were observed at 30 days (
P
=0.76). At 1 year, LEF-LG patients with ≥moderate MR had an adjusted 3-fold higher rate of all-cause mortality (11.5% versus 38.1%; adjusted hazard ratio, 3.27 [95% confidence interval, 1.31–8.15];
P
=0.011), as compared with LEF-LG patients with ≤mild MR. Mortality was mainly driven by cardiac death (adjusted hazard ratio, 4.62;
P
=0.005). As compared with LEF-LG patients with ≥moderate MR assigned to medical therapy, LEF-LG patients with ≥moderate MR undergoing TAVI had significantly lower all-cause mortality (hazard ratio, 0.38; 95% confidence interval, 0.019–0.75) at 1 year.

Conclusions—

Moderate or severe MR is a strong independent predictor of late mortality in LEF-LG patients undergoing TAVI. However, LEF-LG patients assigned to medical therapy have a dismal prognosis independent of MR severity suggesting that TAVI should not be withheld from symptomatic patients with LEF-LG severe aortic stenosis even in the presence of moderate or severe MR.
Effect of a Stable Angiotensin‐(1–7) Analogue on Progenitor Cell Recruitment and Cardiovascular Function Post Myocardial Infarction
Authors: Pessôa Bruno Sevá , Becher Peter Moritz , Van Veghel Richard , De Vries René , Tempel Dennie , Sneep Stefan , Van Beusekom Heleen , Van Der Velden Vincent H. J. , Westermann Dirk , Danser A. H. Jan , Roks Anton J. M.
Published: February 2015

Background

Angiotensin‐(1–7) improves cardiac function and remodeling after myocardial infarction (MI). This may involve recruitment of hematopoietic progenitor cells that support angiogenesis. However, angiotensin‐(1–7) is rapidly metabolized in plasma and tissue. The authors investigated in mice the effect of a metabolically stable angiotensin‐(1–7) analogue, cyclic angiotensin‐(1–7), on progenitor cell recruitment and on the heart post MI, when given in the angiogenesis phase of remodeling.

Methods and Results

Angiogenic progenitor cell recruitment was measured by using flow cytometry 24 and 72 hours after a daily bolus injection of cyclic angiotensin‐(1–7) in healthy C57BL/6 mice. Further, mice underwent MI or sham surgery and subsequently received saline or 2 different doses of cyclic angiotensin‐(1–7) for 3 or 9 weeks. Cyclic angiotensin‐(1–7) increased circulating hematopoietic progenitor cells at 24 hours but not 72 hours. Post MI, cyclic angiotensin‐(1–7) diminished cardiomyocyte hypertrophy and reduced myogenic tone, without altering cardiovascular function or cardiac histology at 9 weeks. Importantly, cyclic angiotensin‐(1–7)–treated mice had reduced cardiac capillary density at 3 weeks after MI but not after 9 weeks. Finally, cyclic angiotensin‐(1–7) decreased tube formation by cultured human umbilical vein endothelial cells.

Conclusions

Our results suggest that cyclic angiotensin‐(1–7), when given early after MI, recruits progenitor cells but does not lead to improved angiogenesis, most likely because it simultaneously exerts antiangiogenic effect in adult endothelial cells. Apparently, optimal treatment with cyclic angiotensin‐(1–7) depends on the time point of onset of application after MI.
No Relationship of Lipid-Lowering Agents to Hematoma Growth
Authors: Priglinger Miriam , Arima Hisatomi , Anderson Craig , Krause Martin
Published: February 2015

Background and Purpose—

Controversy persists over statins and risk of intracerebral hemorrhage. We determined associations of premorbid lipid-lowering therapy and outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT).

Methods—

The pooled data of INTERACT 1 and 2 (international, multicenter, prospective, open, blinded end point, randomized controlled trials of patients with intracerebral hemorrhage [<6 hours] and elevated systolic blood pressure) were analyzed with regard to associations of baseline lipid-lowering treatment and clinical outcomes of 3184 participants in a multivariate model. Associations of lipid-lowering therapy and hematoma growth (baseline to 24 hours) in computed tomographic substudies participants (n=1310) were estimated in ANCOVA.

Results—

Among 204 patients (6.5%) with baseline lipid-lowering treatment, 90-day clinical outcomes were not significantly different after adjustment for confounding variables including region and age. In the computed tomographic substudy, 24-hour hematoma growth was greater in 124 patients (9%) with, compared with those without, prior lipid-lowering therapy. However, this association was not significant between groups (9.2 versus 6.8 mL;
P
<0.13), after adjustment for prior antithrombotic therapy.

Conclusions—

No independent associations were found between lipid-lowering medication and adverse outcomes in patients with intracerebral hemorrhage.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00226096 and NCT00716079.
Methodological Factors in Determining Rates of Dementia in Transient Ischemic Attack and Stroke
Authors: Pendlebury Sarah T. , Chen Ping-Jen , Bull Linda , Silver Louise , Mehta Ziyah , Rothwell Peter M.
Published: February 2015

Background and Purpose—

Many previous studies on dementia in stroke have restrictive inclusion criteria, which may result in underestimation of dementia rates. We undertook a large prospective population-based study of all transient ischemic attack and stroke to determine the impact of study entry criteria on measured rates of pre- and postevent dementia.

Methods—

All patients with acute transient ischemic attack or stroke from a defined population of 92 728 are referred from primary care or at hospital admission to the Oxford Vascular Study (2002–2007) and have baseline clinical and cognitive assessment and follow-up. We examined the impact of early death, other nonavailability, and commonly used selection criteria, on measured rates of dementia.

Results—

Among 1236 patients (mean age/SD 75.2/12.1 years, 582 men, 403 transient ischemic attack), 139 died or were otherwise unavailable for baseline assessment, 319 had prior dependency, 425 had comorbidity, 512 were aged ≥80 years, 85 were dysphasic, and 502 were hospitalized. Pre-event dementia was 3-fold higher in patients dying preascertainment (10/47, 21%) and twice as high in other nonassessed (14/92, 15%) versus assessed patients (69/1097, 6%;
P
=0.0006 and
P
=0.002) and was several-fold higher in those with prior functional impairment (24% versus 3%;
P
<0.0001), age >80 years (13% versus 3%;
P
<0.0001), dysphasia (11% versus 7%;
P
<0.0001), and comorbidity (10% versus 6%;
P
=0.04). Findings for postevent dementia were similar: prior functional impairment (40% versus 13%;
P
<0.0001), age >80 years (28% versus 10%;
P
<0.0001), dysphasia (39% versus 15%; P<0.0001), and comorbidity (20% versus 15%; P=0.04).

Conclusions—

Exclusion of patients unavailable for assessment, and other widely used selection criteria, results in underestimation of the measured rate of dementia associated with transient ischemic attack and stroke.
Effects of Blood Pressure–Lowering Treatment in Different Subtypes of Acute Ischemic Stroke
Authors: Sandset Else Charlotte , Jusufovic Mirza , Sandset Per Morten , Bath Philip M.W. , Berge Eivind
Published: February 2015

Background and Purpose—

The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of blood pressure–lowering treatment with candesartan in acute stroke. We have investigated whether the effect of treatment is different in different subtypes of ischemic stroke.

Methods—

SCAST was a randomized- and placebo-controlled trial of candesartan in 2029 patients presenting within 30 hours of ischemic or hemorrhagic stroke and systolic blood pressure ≥140 mm Hg. Ischemic stroke subtype was categorized by the Oxfordshire Community Stroke Project classification. There were 2 primary effect variables: the composite vascular end point of vascular death, myocardial infarction, or stroke during the first 6 months and functional outcome at 6 months.

Results—

A total of 1733 patients with ischemic stroke were included: total anterior circulation infarcts in 129, partial anterior in 850, posterior in 236, and lacunar in 510 patients. For functional outcome there was a significant trend toward a better effect of candesartan in patients with larger infarcts (total anterior circulation or partial anterior circulation) than in patients with smaller infarcts (lacunar infarction;
P
=0.02). For the composite vascular end point, there were no differences in treatment effect.

Conclusions—

The results suggest that the effect of blood pressure–lowering treatment with candesartan may differ according to different types of acute ischemic stroke, but this needs to be confirmed in future trials.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00120003.
Vox Theologiae
Authors: Eglinton James
Published: February 2015

This article explores the sense in which Christian theology should speak in a manner befitting its nature and content: namely, with humility and boldness in equipoise. The article uses the term vox theologiae (the voice of theology) to do so. The article builds on the works of Herman Bavinck and Karl Barth and various earlier theological approaches to virtue and aesthetics, in order to understand the particulars of theology’s voice. As such, the article attempts to explain why theology gears its practitioner towards a form of public speech rooted in simultaneous daringness and modesty; in so doing, it enters public theology with a particular focus on the place of dogmatics (as a distinct theological discipline) in the public realm.
Touching the Future
Authors: Pennington Emily
Published: February 2015

Christian models of eschatology have often aligned ultimate, perfected existence with immateriality and disembodiment, and have subsequently devalued materiality and embodiment; This is particularly problematic for women’s bodies given their patriarchal alignment with materiality. In response to this problem, this article rethinks the relationship between eschatology and the female body. It asserts that present embodiments are valuable and valued by God, and thus that women’s bodies can be trusted and can add substance to the anticipation of the future. In particular, the article envisions the future through the lens of the maternal body, and therein highlights the eschatological transformation of bodies into abundant life and flourishing. It proposes that this can be both anticipated and created in the present through the practice of touch, as this has the capacity to re-unite dichotomized aspects of existence and to ‘flesh out’ the eschatological affirmation of bodies.
Large-Eddy Simulation of Turbulent Barotropic Flows in Spectral Space on a Sphere
Authors: Azadani L. N. , Staples A. E.
Published: February 2015

Numerical simulations of atmospheric circulation models are limited by their finite spatial resolution, so large-eddy simulation (LES) is a preferred approach to study these models. In LES, a low-pass filter is applied to the flow field to separate the large- and small-scale motions. In implicitly filtered LES, the computational mesh and discretization schemes are considered to be the low-pass filter, while in the explicitly filtered LES approach, the filtering procedure is separated from the grid and discretization operators and allows for better control of the numerical errors. The aim of this paper is to study and compare implicitly filtered and explicitly filtered LES of atmospheric circulation models in spectral space. To achieve this goal, the results of implicitly filtered and explicitly filtered LES of a barotropic atmosphere circulation model on a sphere in spectral space are presented and compared with the results obtained from direct numerical simulation (DNS). Different numerical experiments are performed to investigate the efficiency of explicit filtering over implicit filtering under different dissipation terms and rotation rates. The study shows that explicit filtering increases the accuracy of the computations and improves the results, particularly where the location of coherent structures is concerned, a topic of particular importance in LES of atmospheric flows for climate and weather applications.
Variation of Lightning and Convective Rain Fraction in Mesoscale Convective Systems of the MJO
Authors: Virts Katrina S. , Houze Robert A.
Published: February 2015

Characteristics of mesoscale convective systems (MCSs) in regions affected by the Madden–Julian oscillation (MJO) are investigated using a database of MCSs observed by the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E). Lightning occurrence detected by the World-Wide Lightning Location Network (WWLLN) is composited in a framework centered on the MCSs. During MJO active periods, MCSs are more numerous and larger, as the convective features persist and attain greater horizontal scales. Anomalies of the lifted index, derived from the European Centre for Medium-Range Weather Forecasts (ECMWF) interim reanalysis (ERA-Interim) fields, indicate that MCS environments are more stable during MJO active periods.

Over the Indian Ocean, Maritime Continent, and western Pacific, lightning density in an MCS maximizes during the time that the total number of systems begins to increase as the MJO is beginning to be more active, implying both more vigorous convection and less extensive stratiform rain areas at this transitional time of the MJO. The peak in MJO precipitation coincides with peak occurrence of interconnected MCSs with larger stratiform rain fraction, shown by the Tropical Rainfall Measuring Mission satellite, while composites of lightning frequency show that during MJO active periods the zone of lightning is contracted around the centers of MCSs, and flashes are less frequent.
Determining the Origins of Advective Heat Transport Convergence Variability in the North Atlantic
Authors: Buckley Martha W. , Ponte Rui M. , Forget Gaël , Heimbach Patrick
Published: February 2015

A recent state estimate covering the period 1992–2010 from the Estimating the Circulation and Climate of the Ocean (ECCO) project is utilized to quantify the roles of air–sea heat fluxes and advective heat transport convergences in setting upper-ocean heat content anomalies H in the North Atlantic Ocean on monthly to interannual time scales. Anomalies in (linear) advective heat transport convergences, as well as Ekman and geostrophic contributions, are decomposed into parts that are due to velocity variability, temperature variability, and their covariability. Ekman convergences are generally dominated by variability in Ekman mass transports, which reflect the instantaneous response to local wind forcing, except in the tropics, where variability in the temperature field plays a significant role. In contrast, both budget analyses and simple dynamical arguments demonstrate that geostrophic heat transport convergences that are due to temperature and velocity variability are anticorrelated, and thus their separate treatment is not insightful. In the interior of the subtropical gyre, the sum of air–sea heat fluxes and Ekman heat transport convergences is a reasonable measure of local atmospheric forcing, and such forcing explains the majority of H variability on all time scales resolved by ECCO. In contrast, in the Gulf Stream region and subpolar gyre, ocean dynamics are found to be important in setting H on interannual time scales. Air–sea heat fluxes damp anomalies created by the ocean and thus are not set by local atmospheric variability.
A Dynamical Climate Model–Driven Hydrologic Prediction System for the Fraser River, Canada
Authors: Shrestha Rajesh R. , Schnorbus Markus A. , Cannon Alex J.
Published: February 2015

Recent improvements in forecast skill of the climate system by dynamical climate models could lead to improvements in seasonal streamflow predictions. This study evaluates the hydrologic prediction skill of a dynamical climate model–driven hydrologic prediction system (CM-HPS), based on an ensemble of statistically downscaled outputs from the Canadian Seasonal to Interannual Prediction System (CanSIPS). For comparison, historical and future climate traces–driven ensemble streamflow prediction (ESP) was employed. The Variable Infiltration Capacity model (VIC) hydrologic model setup for the Fraser River basin, British Columbia, Canada, was used as a test bed for the two systems. In both cases, results revealed limited precipitation prediction skill. For streamflow prediction, the ESP approach has very limited or no correlation skill beyond the months influenced by initial hydrologic conditions, while the CM-HPS has moderately better correlation skill, attributable to the enhanced temperature prediction skill that results from CanSIPS’s ability to predict El Niño–Southern Oscillation (ENSO) and its teleconnections. The root-mean-square error, bias, and categorical skills for the two methods are mostly similar. Hydrologic modeling uncertainty also affects the prediction skill, and in some cases prediction skill is constrained by hydrologic model skill. Overall, the CM-HPS shows potential for seasonal streamflow prediction, and further enhancements in climate models could potentially to lead to more skillful hydrologic predictions.
Transport of Surface Freshwater from the Equatorial to the Subtropical North Atlantic Ocean
Authors: Foltz Gregory R. , Schmid Claudia , Lumpkin Rick
Published: February 2015

The transport of low-salinity water northward in the tropical and subtropical North Atlantic Ocean influences upper-ocean stratification, vertical mixing, and sea surface temperature (SST). In this study, satellite and in situ observations are used to trace low-salinity water northward from its source in the equatorial Atlantic and to examine its modification through air–sea fluxes and vertical mixing. In contrast to gridded climatologies, which depict a gradual northward dispersal of surface freshwater from the equatorial Atlantic, satellite observations and direct measurements from four moorings in the central tropical North Atlantic show a distinct band of surface freshwater moving northward from the equatorial Atlantic during boreal fall through spring, with drops in sea surface salinity (SSS) of 0.5–2.5 psu in the span of one to two weeks as the low SSS front passes. The ultimate low-latitude source of the low SSS water is found to be primarily Amazon River discharge west of 40°W and rainfall to the east. As the low-salinity water moves northward between 8° and 20°N during October–April, 70% of its freshwater in the upper 20 m is lost to the combination of evaporation, horizontal eddy diffusion, and vertical turbulent mixing, with an implied rate of SSS damping that is half of that for SST. During 1998–2012, interannual variations in SSS along 38°W are found to be negatively correlated with the strength of northward surface currents. The importance of ocean circulation for interannual variations of SSS and the small damping time scale for SSS emphasize the need to consider meridional freshwater advection when interpreting SSS variability in the tropical–subtropical North Atlantic.
Ensemble-Based Error and Predictability Metrics Associated with Tropical Cyclogenesis. Part II: Wave-Relative Framework
Authors: Komaromi William A. , Majumdar Sharanya J.
Published: February 2015

The predictability of selected variables associated with tropical cyclogenesis is examined using 10-day ECMWF ensemble forecasts for 21 events from the 2010 Atlantic hurricane season. Variables are associated with the strength of the pregenesis disturbance, quantified via circulation and thickness anomaly, and the favorability of the immediate environment via moisture and vertical wind shear.

For approximately half of the cases, the predicted strength of the genesis signal is directly related to the predicted favorability of the environment. For the remainder of the cases, predictability is more directly associated with the strength and location of the analyzed disturbance. Some commonalities among the majority of the sample are also observed. Forecast joint distributions demonstrate that 700-hPa relative humidity of less than 60% within 300 km of the circulation center is a limiting factor for genesis. Genesis is also predicted and found to occur in the presence of significant wind shear (~15 m s−1), but almost exclusively when the core and environment of the wave are both very moist.

The ensemble also demonstrates the potential to predict error standard deviation of variables averaged within 300- and 1000-km radii about individual tropical waves. Forecasts with greater ensemble standard deviation tend to be, on average, associated with greater mean error, especially for forecasts of less than 7 days. However, model biases, particularly a dry core and weak circulation bias, become pronounced at longer lead times. Overall, these results demonstrate that both the environmental conditions favorable to genesis and the genesis events themselves may be predictable to a week or more.
Evaluation of Forecast Performance of Asian Summer Monsoon Low-Level Winds Using the TIGGE Dataset
Authors: Niu Ruoyun , Zhai Panmao , Zhou Baiquan
Published: February 2015

The forecast performances of the East Asian summer monsoon (EASM) and South Asian summer monsoon (SASM) by six THORPEX Interactive Grand Global Ensemble (TIGGE) centers during the summers of 2008–13 were evaluated to reflect the current predictability of state-of-the-art numerical weather prediction. The results show that the EASM is overestimated by all TIGGE centers except the Canadian Meteorological Centre (CMC). The SASM is overestimated by the European Centre for Medium-Range Weather Forecasts (ECMWF), the China Meteorological Administration (CMA), and the CMC, but is underpredicted by the Japan Meteorological Agency (JMA). Additionally, the SASM is overestimated for early lead times and underestimated for longer lead times by the National Centers for Environmental Prediction (NCEP) and the Met Office (UKMO). Further analysis suggests that such biases are likely associated with land–sea thermal contrasts. The EASM surge is overestimated by the NCEP and CMA and mainly underestimated by the others. The bias predictabilities for the SASM surge are similar to those of the SASM. The peaks of the SASM and EASM, including their surges, are mainly underestimated, whereas the valleys are mostly overestimated. Overall, the ECMWF and UKMO have the highest forecast skill in predicting the SASM and EASM and both have respective advantages. The TIGGE centers generally show higher skill in predicting the SASM than the EASM, and their skill in forecasting the SASM and EASM is superior to that for their respective surges. Moreover, bias-correction forecast skills show improvement with higher correlation coefficients in raw forecast verification.
Tea consumption and the risk of depression: A meta-analysis of observational studies
Authors: Dong Xiaoxin , Yang Chen , Cao Shiyi , Gan Yong , Sun Huilian , Gong Yanhong , Yang Huajie , Yin Xiaoxu , Lu Zuxun
Published: February 2015

Objective:

Whether tea consumption decreases the risk of depression remains controversial. We performed a meta-analysis of findings from observational studies to evaluate the association between tea consumption and depression risk.

Method:

Embase, PubMed, and Chinese National Knowledge Infrastructure databases were searched from their inception through August 2014 for observational studies that had reported the association between tea consumption and depression risk. We used a fixed effects model when heterogeneity was negligible and a random effect model when heterogeneity was significant to calculate the summary relative risk estimates (RRs) and 95% confidence intervals (CIs).

Results:

Eleven studies with 13 reports were eligible for inclusion in the meta-analysis (22,817 participants with 4,743 cases of depression). Compared to individuals with lower tea consumption, those with higher tea consumption had a pooled RR of depression risk at 0.69 (95% CI: 0.63–0.75). Eight reports were included in the dose–response analysis of tea consumption and depression risk (10,600 participants with 2,107 cases). There was a linear association between tea consumption and the risk of depression, with an increment of 3 cups/day in tea consumption associated with a decrease in the risk of depression of 37% (RR = 0.63, 95% CI: 0.55–0.71).

Conclusion:

Tea consumption is associated with a decreased risk of depression.
Courtroom Perceptions of Child Sexual Assault
Authors: Golding Jonathan M. , Lynch Kellie R. , Wasarhaley Nesa E. , Keller Peggy S.
Published: February 2015

One hundred eighty-two undergraduates (96 women) read a summary of a child sexual assault (CSA) criminal trial involving a 6-year-old alleged victim. The trial summaries differed as to whether an eyewitness to the CSA other than the victim testified in court and the age of that eyewitness (6 or 36 years old). The results showed that the additional witness did not affect women’s pro-victim judgments, but significantly increased men’s pro-victim judgments. Furthermore, compared with women, men felt more anger toward the defendant when the additional witness testified. A follow-up experiment (43 women) included an additional witness who did not witness the CSA. The results of this follow-up showed that rather than the number of witnesses, it was the additional witness to the CSA that increased pro-victim judgments. The results are discussed in terms of how additional corroborating testimony in a CSA case affects men and women jurors.
Initial Validation of an Instrument Measuring Psychology-Specific Epistemological Beliefs
Authors: Renken Maggie D. , McMahan Ethan A. , Nitkova Martina
Published: February 2015

Psychology-specific epistemological beliefs (EBs) are believed to influence students’ approach to and performance in psychology courses. However, empirical research on this topic is limited due in part to a lack of well-validated instruments measuring this construct. The primary objective of this research was to develop and validate the Psychology-Specific Epistemological Belief Scale (Psych-SEBS), a short self-report instrument measuring psychology-specific EBs. Study 1 addresses the structural validity, internal consistency, test–retest reliability, and convergent validity of the Psych-SEBS. Study 2 addresses the criterion-related and incremental validity of the Psych-SEBS. Findings indicated acceptable psychometric properties of this 13-item instrument and its three subscales, namely, significance of psychology research, subjective nature of psychology knowledge, and predictability of human behavior. Scores on Psych-SEBS scales were significantly associated with construct-relevant outcomes, including student interest and performance in psychology courses, and explained unique variance in these outcomes beyond that explained by existing instruments.
The Disappearance of Independence in Textbook Coverage of Asch’s Social Pressure Experiments
Authors: Griggs Richard A.
Published: February 2015

Asch’s classic social pressure experiments are discussed in almost all introductory and social psychology textbooks. However, the results of these experiments have been shown to be misrepresented in textbooks. An analysis of textbooks from 1953 to 1984 revealed that although most of the responses on critical trials were independent correct ones, textbooks have increasingly over time emphasized the minority conformity responding and deemphasized the majority independent responding. An analysis of 20 introductory psychology textbooks and 10 introductory social psychology textbooks revealed that this distorted coverage has not only persisted but increased over the past 30 years. Given the entrenchment of such coverage in current texts, a suggestion for how to address this distorted coverage without major text revision is provided.