bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of the laryngeal tube disposable by paramedics during out-of-hospital cardiac arrest: a prospectively observational study (2008–2012)
Authors: Müller Jens-Uwe , Semmel Thomas , Stepan Roland , Seyfried Timo F , Popov Aron F , Graf Bernhard M , Wiese Christoph H R 
Published: January 2013

SummaryIn the previous and the current guidelines of the European Resuscitation Council (ERC), endotracheal intubation (ETI), as an instrument for ventilation during resuscitation, was confirmed as less important for paramedics not trained in this method. For those, during resuscitation, the laryngeal tube is recommended by the ERC as a supraglottic airway device. The present study investigated prospectively the use of the laryngeal tube disposable (LT-D) by paramedics in prehospital emergency cases.MethodsDuring a 42-month period (Sept 2008–Feb 2012), we prospectively registered all prehospital cardiac arrest situations in which the LT-D had been applied by paramedics (from one emergency medical service in Germany).ResultsDuring the defined period, 133 attempts, recorded on standardised data sheets, were enrolled into the investigation. Three were excluded from the study because of use during a trauma situation. Therefore, 130 patients were evaluated in this study. For this, the LT-D was used in 98% of all cases during resuscitation, and in about 2% of other emergencies (eg, trauma). With regard to resuscitation, adequate ventilation/oxygenation was described as possible in 83% of all included cases. In 66% of all cases, no problems concerning the insertion of the LT-D were described by the paramedics. No significant problems were reported in 93%. In 7% (n=9 cases), no insertion of the LT-D was possible. Instead of bag-mask-valve ventilation, the LT-D was used as a first-line airway device in about 66%. Between the two defined groups, no statistically significant differences were found (p>0.05).ConclusionsAs an alternative airway device during resuscitation, recommended by the ERC in 2005 and 2010, the LT-D may enable ventilation rapidly and, as in most of our described cases, effectively. Additionally, by using the LT-D in a case of cardiac arrest, a reduced ‘hands-off time’ and, therefore, a high chest compression rate may be possible. Our investigation showed that the LT-D was often used as an alternative to bag-mask-ventilation and to ETI as well. However, we were able to describe more problems in the use of the LT-D than earlier investigations. Therefore, in future, more studies concerning the use of alternative airway devices in comparison with ETI and/or video-laryngoscopy seem to be necessary.
Control-theoretic cyber-physical system modeling and synthesis
Authors: Shin Donghwa , Park Jaehyun , Kim Younghyun , Seo Jaeam , Chang Naehyuck 
Published: January 2013

A joint optimization of the physical system and the cyber world is one of the key problems in the design of a cyber-physical system (CPS). The major mechanical forces and/or chemical reactions in a plant are commonly modified by actuators in the balance-of-plant (BOP) system. More powerful actuators requires more power, but generally increase the response of the physical system powered by the electrical energy generated by the physical system. To maximize the overall output of a power generating plant therefore requires joint optimization of the physical system and the cyber world, and this is a key factor in the design of a CPS.
We introduce a systematic approach to the modeling and synthesis of a CPS that emphasize joint power optimization, using an active direct methanol fuel cell (DMFC) as a case study. Active DMFC systems are superior to passive DMFCs in terms of fuel efficiency thanks to their BOP system, which includes pumps, air blowers, and fans. However, designing a small-scale active DMFC with the best overall system efficiency requires the BOP system to be jointly optimized with the DMFC stack operation, because the BOP components are powered by the stack. Our approach to this synthesis problem involves i) BOP system characterization, ii) integrated DMFC system modeling, iii) configuring a system for the maximum net power output through design space exploration, iv) synthesis of feedback control tasks, and v) implementation.
Electric grid balancing through lowcost workload migration
Authors: Chiu David , Stewart Christopher , McManus Bart 
Published: January 2013

Energy production must continuously match demand on the electric grid. A deficiency can lead to service disruptions, and a surplus can place tremendous stress on grid components, potentially causing major blackouts. To manage this balance, grid operators must increase or lower power generation, with only a few minutes to react. The grid balancing problem has also impeded the pace of integrating bountiful renewable resources (e.g., wind), whose generation is intermittent. An emerging plan to mitigate this problem is demand response, i.e., for grid operators to alter the electricity usage behavior of the masses through real-time price signals. But due to prohibitively high infrastructure costs and societal-scale adoption, tangible demand response mechanisms have so far been elusive.
We believe that altering the usage patterns of a multitude of data centers can be a tangible, albeit initial, step towards affecting demand response. Growing in both density and size, today's data center designs are shaped by the increasing awareness of energy costs and carbon footprint. We posit that shifting computational workloads (and thus, demand) across geographic regions to match electricity supply may help balance the grid. In this paper we will first present a real grid balancing problem experienced in the Pacfic Northwest. We then propose a symbiotic relationship between data centers and grid operators by showing that mutual cost benefits can be accessible. Finally, we argue for a low cost workload migration mechanism, and pose overarching challenges in designing this framework.
Memory management for many-core processors with software configurable locality policies
Authors: Zhou Jin , Demsky Brian 
Published: January 2013

As processors evolve towards higher core counts, architects will develop more sophisticated memory systems to satisfy the cores' increasing thirst for memory bandwidth. Early many-core processor designs suggest that future memory systems will likely include multiple controllers and distributed cache coherence protocols. Many-core processors that expose memory locality policies to the software system provide opportunities for automatic tuning that can achieve significant performance benefits.
Managed languages typically provide a simple heap abstraction. This paper presents techniques that bridge the gap between the simple heap abstraction of modern languages and the complicated memory systems of future processors. We present a NUMA-aware approach to garbage collection that balances the competing concerns of data locality and heap utilization to improve performance. We combine a lightweight approach for measuring an application's memory behavior with an online, adaptive algorithm for tuning the cache to optimize it for the specific application's behaviors.
We have implemented our garbage collector and cache tuning algorithm and present results on a 64-core TILEPro64 processor.
BRAF Inhibition Is Associated with Enhanced Melanoma Antigen Expression and a More Favorable Tumor Microenvironment in Patients with Metastatic Melanoma
Authors: Frederick Dennie T. , Piris Adriano , Cogdill Alexandria P. , Cooper Zachary A. , Lezcano Cecilia , Ferrone Cristina R. , Mitra Devarati , Boni Andrea , Newton Lindsay P. , Liu Chengwen , Peng Weiyi , Sullivan Ryan J. , Lawrence Donald P. , Hodi F. Stephen , Overwijk Willem W. , Lizée Gregory , Murphy George F. , Hwu Patrick , Flaherty Keith T. , Fisher David E. , Wargo Jennifer A. 
Published: January 2013

Abstract
Purpose: To evaluate the effects of BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma.
Experimental Design: Thirty-five biopsies were collected from 16 patients with metastatic melanoma pretreatment (day 0) and at 10 to 14 days after initiation of treatment with either BRAF inhibitor alone (vemurafenib) or BRAF + MEK inhibition (dabrafenib + trametinib) and were also taken at time of progression. Biopsies were analyzed for melanoma antigens, T-cell markers, and immunomodulatory cytokines.
Results: Treatment with either BRAF inhibitor alone or BRAF + MEK inhibitor was associated with an increased expression of melanoma antigens and an increase in CD8+ T-cell infiltrate. This was also associated with a decrease in immunosuppressive cytokines [interleukin (IL)-6 and IL-8] and an increase in markers of T-cell cytotoxicity. Interestingly, expression of exhaustion markers TIM-3 and PD1 and the immunosuppressive ligand PDL1 was increased on treatment. A decrease in melanoma antigen expression and CD8 T-cell infiltrate was noted at time of progression on BRAF inhibitor alone and was reversed with combined BRAF and MEK inhibition.
Conclusions: Together, these data suggest that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T-cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T-cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma. Clin Cancer Res; 19(5); 1225–31. ©2013 AACR.
New Strategies in the Treatment of Ovarian Cancer: Current Clinical Perspectives and Future Potential
Authors: Banerjee Susana , Kaye Stanley B. 
Published: January 2013

Abstract
The treatment of ovarian cancer is set to undergo rapid changes, as strategies incorporating molecular targeted therapies begin to take shape. These are based on a better appreciation of approaches targeting the tumor microenvironment as well as specific subtypes of the disease, with distinct molecular aberrations. Targeting the VEGF pathway through bevacizumab is clearly effective, with positive randomized trials at all disease stages; targeting defective homologous recombination repair pathways with PARP inhibitors is also proving successful in a substantial proportion of patients with high-grade serous ovarian cancer. In this article, we will review progress in these two leading areas and also discuss the potential for targeting other pathways and receptors that may be activated in ovarian cancer, including the RAS/RAF/MEK and PI3K/AKT/mToR pathways, the ErbB and IGF family of receptors, mitotic check points, and also the folate receptor. Here, single-agent therapy may play a role in selected cases but essential components of future strategies should include combination treatments aimed at dealing with the key problem of drug resistance, together with rational approaches to patient selection. Clin Cancer Res; 19(5); 961–8. ©2013 AACR.
The influence of factor V Leiden and G20210A prothrombin mutation on the presence of residual vein obstruction after idiopathic deep-vein thrombosis of the lower limbs
Authors: Legnani Cristina , Pengo Vittorio , Ghirarduzzi Angelo , Testa Sophie , Poli Daniela , Prisco Domenico , Tripodi Armando , Palareti Gualtiero , Cosmi Benilde ,   for the PROLONG Investigators FCSA, Italian Federation of Anticoagulation Clinics
Published: January 2013

SummaryIt was our aim to assess whether factor V Leiden (FVL) and G20210A prothrombin (FII) mutation are associated with the presence of residual vein obstruction (RVO) after a standard course of anticoagulation for a first episode of idiopathic proximal deep-vein thrombosis (DVT) of the lower limbs, with or without symptomatic pulmonary embolism (PE). Patients were enrolled in two prospective multicentre studies: PROLONG and PROLONG II. RVO was detected by compression ultra-sonography according to the method of Prandoni on the day of anticoagulation withdrawal. Patients were also screened for FVL and FII mutation. The presence of FVL and/or FII mutation was determined in 872/963 (90.5%) patients, in 753 of whom RVO was assessed. FVL was significantly less frequent among subjects with isolated PE (7/176:4%) than among patients with either DVT and PE (15/133:11.3%; p=0.0018) or isolated DVT (89/563:15.8%; p<0.0001), confirming the FVL paradox. The rate of FII mutation was similar among patients with isolated PE (11/176:6.2%) and patients with either DVT and PE (12/133:9%) or isolated DVT (52/563:9.2%). FVL and FII mutation were not significantly associated with RVO at the multivariate analysis in all patients, although data suggest that FVL and FII mutation may have a differential effect on RVO in the subgroups of patients with DVT and DVT plus PE patients. Male sex and isolated DVT were significantly associated with RVO in all patients. In conclusion, male sex and isolated DVT are associated with RVO, while FVL and FII mutations are not significantly associated with RVO in this study.
Vascular Function During Prolonged Progression and Regression of Atherosclerosis in Mice
Authors: Miller Jordan D. , Chu Yi , Castaneda Lauren E. , Serrano Kristine M. , Brooks Robert M. , Heistad Donald D. 
Published: January 2013

Objective—
Endothelial dysfunction is associated with atherosclerosis in mice, but it is difficult to reduce cholesterol levels enough to study regression of atherosclerosis in genetically modified mice. The goal of this study was to examine vascular structure and function before and after reducing elevated plasma lipid levels with a genetic switch in Reversa mice, and identify novel mechanisms contributing to structural and functional improvements in the vasculature after reduction of blood lipids.

Methods and Results—
After 6 months of hypercholesterolemia, endothelial function (maximum relaxation to acetylcholine) in aorta was impaired and responses to nitric oxide were unaffected. Further impairment in endothelial function was observed after 12 months of hypercholesterolemia and was associated with reductions in sensitivity to nitric oxide. Expression of dihydrofolate reductase was reduced at 6 and 12 months, and addition of the tetrahydrobiopterin precursor sepiapterin significantly improved endothelial function. Reducing cholesterol levels at 6 months normalized dihydrofolate reductase expression and prevented further impairment in endothelial function. Similar functional changes were observed after 12 months of hypercholesterolemia followed by 2 months of lipid lowering.

Conclusion—
Our data suggest that endothelial dysfunction after prolonged hypercholesterolemia is the result of both impairment of sensitivity to nitric oxide and reduced nitric oxide synthase cofactor bioavailability. Both of these changes can be prevented by normalizing blood lipids during moderately severe or advanced atherosclerosis.
Diabetes Causes Bone Marrow Endothelial Barrier Dysfunction by Activation of the RhoA–Rho-Associated Kinase Signaling Pathway
Authors: Mangialardi Giuseppe , Katare Rajesh , Oikawa Atsuhiko , Meloni Marco , Reni Carlotta , Emanueli Costanza , Madeddu Paolo 
Published: January 2013

Objective—
Diabetes mellitus causes bone marrow (BM) microangiopathy. This study aimed to investigate the mechanisms responsible for BM endothelial dysfunction in diabetes mellitus.

Methods and Results—
The analysis of differentially expressed transcripts in BM endothelial cells (BMECs) from type-1 diabetic and nondiabetic mice showed an effect of diabetes mellitus on signaling pathways controlling cell death, migration, and cytoskeletal rearrangement. Type-1 diabetic-BMECs displayed high reactive oxygen species levels, increased expression and activity of RhoA and its associated protein kinases Rho-associated kinase 1/Rho-associated kinase 2, and reduced Akt phosphorylation/activity. Likewise, diabetes mellitus impaired Akt-related BMEC functions, such as migration, network formation, and angiocrine factor-releasing activity, and increased vascular permeability. Moreover, high glucose disrupted BMEC contacts through Src tyrosine kinase phosphorylation of vascular endothelial cadherin. These alterations were prevented by constitutively active Akt (myristoylated Akt), Rho-associated kinase inhibitor Y-27632, and Src inhibitors. Insulin replacement restored BMEC abundance, as assessed by flow cytometry analysis of the endothelial marker MECA32, and endothelial barrier function in BM of type-1 diabetic mice.

Conclusion—
Redox-dependent activation of RhoA/Rho-associated kinase and Src/vascular endothelial cadherin signaling pathways, together with Akt inactivation, contribute to endothelial dysfunction in diabetic BM. Metabolic control is crucial for maintenance of endothelial cell homeostasis and endothelial barrier function in BM of diabetic mice.
T-Helper 2 Immunity Is Associated With Reduced Risk of Myocardial Infarction and Stroke
Authors: Engelbertsen Daniel , Andersson Linda , Ljungcrantz Irena , Wigren Maria , Hedblad Bo , Nilsson Jan , Björkbacka Harry 
Published: January 2013

Objective—
Experimental studies in mice have attributed T-helper (Th) 1 and Th2 cells important roles in atherosclerosis, but the clinical importance of these cells in cardiovascular disease (CVD) remains to be clarified. Here, we investigated associations between Th1 and Th2 cells, carotid intima-media thickness, and cardiovascular risk.

Methods and Results—

Blood drawn at baseline and incident cardiovascular events during 15-year follow-up were assessed in 700 participants. Baseline Th1 (CD3
+
CD4
+
interferon-γ
+
) and Th2 (CD3
+
CD4
+
interleukin-4
+
) cells were analyzed by flow cytometry, and cytokine-release from activated mononuclear leukocytes was measured by multiplex technology. High numbers of Th2 cells were independently associated with decreased mean common carotid intima-media thickness. High numbers of Th2 cells were also independently associated with a reduced risk of acute myocardial infarction in women (hazard ratio, 0.19; 95% confidence interval, 0.06–0.56;
P
=0.002 for the highest versus the lowest tertile of Th2 cells). Moreover, release of the Th2 cytokine interleukin-4 from activated mononuclear leukocytes was independently associated with a reduced risk of CVD. No independent associations between Th1 cells and carotid intima-media thickness or CVD risk were found.

Conclusion—
Our observations provide the first clinical evidence for a protective role of Th2 immunity in CVD. They also suggest this protection is more prominent in women than in men. In spite of convincing evidence from experimental studies, we found no support for a role of Th1 immunity in CVD.
Effect of Low-Dose Aspirin on Functional Outcome From Cerebral Vascular Events in Women
Authors: Rist Pamela M. , Buring Julie E. , Kase Carlos S. , Kurth Tobias 
Published: January 2013

Background and Purpose—
Although aspirin is effective in prevention of stroke, fewer studies have examined the impact of aspirin on stroke morbidity.

Methods—
The Women’s Health Study is a completed randomized, placebo-controlled trial designed to test the effect of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer, which enrolled 39 876 women. We used multinomial logistic regression to evaluate the relationship between randomized aspirin assignment and functional outcomes from stroke. Possible functional outcomes were neither stroke nor transient ischemic attack (TIA), modified Rankin scale (mRS) score 0 to 1, 2 to 3, and 4 to 6.

Results—
After a mean of 9.9 years of follow-up, 460 confirmed strokes (366 ischemic, 90 hemorrhagic, and 4 unknown type) and 405 confirmed TIAs occurred. With regard to total and ischemic stroke, women who were randomized to aspirin had a nonsignificant decrease in risk of any outcome compared to women not randomized to aspirin. This decrease in risk only reached statistical significance for those experiencing TIA compared to participants without stroke or TIA (odds ratio=0.77; 95% confidence interval, 0.63–0.94). For hemorrhagic stroke, a nonsignificant increase in the risk of achieving an mRS score 2 to 3 or 4 to 6 compared with no stroke or TIA was observed for the women randomized to aspirin compared to those randomized to placebo.

Conclusions—
Results from this large randomized clinical trial provide evidence that 100 mg of aspirin every other day may reduce the risk of ischemic cerebral vascular events but does not have differential effects on functional outcomes from stroke.
Carotid Atherosclerosis and Risk of Subsequent Coronary Event in Outpatients With Atherothrombosis
Authors: Sirimarco Gaia , Amarenco Pierre , Labreuche Julien , Touboul Pierre-Jean , Alberts Mark , Goto Shinya , Rother Joachim , Mas Jean-Louis , Bhatt Deepak L. , Steg Philippe Gabriel 
Published: January 2013

Background and Purpose—
The presence of carotid plaque reflects overall atherosclerotic burden and may predict coronary artery disease events. We examined the association among carotid atherosclerosis, history of atherothrombotic events, and risk of coronary events.

Methods—
Among 45 227 patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry with 4-year follow-up, 23 364 patients with information on carotid atherosclerosis at baseline were analyzed. The primary outcome was the composite of first occurrence of cardiovascular death, myocardial infarction, or coronary hospitalization.

Results—

The carotid atherosclerosis was present in 46% of patients (n=10 725) and was associated with increasing conventional cardiovascular risk factors and extent of symptomatic vascular disease. During 4-year follow-up, 4304 patients experienced ≥1 coronary event. After adjustment for cardiovascular risk factors and geographic region, the risk of coronary events increased by 22% (95% confidence interval [CI], 14%–30%) in patients with versus without carotid atherosclerosis. The relative increase was 18% (95% CI, –7%–51%) in patients enrolled with multiple risk factors only, 25% (95% CI,16%–35%) in patients with coronary artery disease, 46% (95% CI,28%–65%) in patients with cerebrovascular disease, and 37% (95% CI,17%–60%) in patients with peripheral artery disease. Carotid atherosclerosis was associated with increased risk, even among patients with previous myocardial infarction but no known stroke (
P
=0.001) or among patients with previous stroke but no known myocardial infarction (
P
<0.001).

Conclusions—
Carotid atherosclerosis was an independent predictor of coronary events across all types of symptomatic vascular disease and had an incremental effect on risk regardless of risk factors or location of vessel disease.