bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Magnetic Resonance Imaging Pericardial Late Gadolinium Enhancement and Elevated Inflammatory Markers Can Predict the Reversibility of Constrictive Pericarditis After Antiinflammatory Medical Therapy
Authors: Feng DaLi , Glockner James , Kim Kyehun , Martinez Matthew , Syed Imran S. , Araoz Philip , Breen Jerome , Espinosa Raul E. , Sundt Thoralf , Schaff Hartzell V. , Oh Jae K.
Published: October 2011

Background—

Constrictive pericarditis (CP) is a disabling disease, and usually requires pericardiectomy to relieve heart failure. Reversible CP has been described, but there is no known method to predict the reversibility. Pericardial inflammation may be a marker for reversibility. As a pilot study, we assessed whether cardiac magnetic resonance imaging pericardial late gadolinium enhancement (LGE) and inflammatory biomarkers could predict the reversibility of CP after antiinflammatory therapy.

Method and Results—

Twenty-nine CP patients received antiinflammatory medications after cardiac magnetic resonance imaging. Fourteen patients had resolution of CP, whereas 15 patients had persistent CP after 13 months of follow-up. Baseline LGE pericardial thickness was greater in the group with reversible CP than in the persistent CP group (4±1 versus 2±1 mm,
P
=0.001). Qualitative intensity of pericardial LGE was moderate or severe in 93% of the group with reversible CP and in 33% of the persistent CP group (
P
=0.002). Cardiac magnetic resonance imaging LGE pericardial thickness ≥3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The group with reversible CP also had higher baseline C-reactive protein and erythrocyte sedimentation rate than the persistent CP group (59±52 versus 12±14 mg/L,
P
=0.04 and 49±25 versus 15±16 mm/h,
P
=0.04, respectively). Antiinflammatory therapy was associated with a reduction in C-reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the group with reversible CP but not in the persistent CP group.

Conclusions—

Reversible CP was associated with pericardial and systemic inflammation. Antiinflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiology and symptoms. Further studies in a larger number of patients are needed.
Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic Stenosis
Authors: Reynolds Matthew R. , Magnuson Elizabeth A. , Lei Yang , Leon Martin B. , Smith Craig R. , Svensson Lars G. , Webb John G. , Babaliaros Vasilis C. , Bowers Bruce S. , Fearon William F. , Herrmann Howard C. , Kapadia Samir , Kodali Susheel K. , Makkar Raj R. , Pichard Augusto D. , Cohen David J. ,   for the Placement of Aortic Transcatheter Valves (PARTNER) Investigators
Published: October 2011

Background—

Transcatheter aortic valve replacement (TAVR) has been shown to improve survival compared with standard therapy in patients with severe aortic stenosis who cannot have surgery. The effects of TAVR on health-related quality of life have not been reported from a controlled study.

Methods and Results—

The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgical valve replacement to TAVR (n=179) or standard therapy (n=179). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health Survey (SF-12). The primary end point was the KCCQ overall summary score (range, 0–100; higher=better). At baseline, mean KCCQ summary scores (35±20) and SF-12 physical summary scores (28±7) were markedly depressed. Although the KCCQ summary score improved from baseline in both groups, the extent of improvement was greater after TAVR compared with control at 1 month (mean between-group difference, 13 points; 95% confidence interval, 8–19;
P
<0.001) with larger benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15–27;
P
<0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19–33;
P
<0.001). At 12 months, TAVR patients also reported higher SF-12 physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (
P
<0.001 for both comparisons).

Conclusions—

Among inoperable patients with severe aortic stenosis, compared with standard care, TAVR resulted in significant improvements in health-related quality of life that were maintained for at least 1 year.

Clinical Trials Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00530894.
Association of Physical Activity With Vascular Endothelial Function and Intima-Media Thickness
Authors: Pahkala Katja , Heinonen Olli J. , Simell Olli , Viikari Jorma S.A. , Rönnemaa Tapani , Niinikoski Harri , Raitakari Olli T.
Published: October 2011

Background—

Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents.

Methods and Results—

FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (
P
for maximum FMD=0.0021,
P
for total FMD response=0.0036) and inversely with IMT (
P
=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (
P
=0.031) and decreased progression of IMT (
P
=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (
P
=0.0072).

Conclusions—

Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00223600 (STRIP19902010).
Gene Transfer of Neuronal Nitric Oxide Synthase to the Paraventricular Nucleus Reduces the Enhanced Glutamatergic Tone in Rats With Chronic Heart Failure
Authors: Zheng Hong , Liu Xuefei , Li Yifan , Sharma Neeru M. , Patel Kaushik P.
Published: October 2011

Our previous studies have shown that the decreased NO and increased glutamatergic mechanisms on sympathetic regulation within the paraventricular nucleus (PVN) may contribute to the elevated sympathoexcitation during chronic heart failure (CHF). In the present study, we investigated the effects of neuronal NO synthase (nNOS) gene transfer on
N
-methyl-
d
-aspartic acid receptor subunit NR
1
in the rats with a coronary ligation model of CHF. Adenovirus vectors encoding nNOS (AdnNOS) or adenovirus vectors encoding β-galactosidase were transfected into the PVN in vivo. Five days after application of AdnNOS, the increased expression of nNOS within the PVN was confirmed by NADPH-diaphorase staining, real-time PCR, and Western blot. In anesthetized rats, AdnNOS treatment significantly enhanced the blunted renal sympathetic nerve activity, blood pressure, and heart rate responses to NO synthase inhibitor
N
G
-monomethyl-
l
-arginine in the rats with CHF compared with CHF-adenovirus vectors encoding β-galactosidase group. AdnNOS significantly decreased the enhanced renal sympathetic nerve activity, blood pressure, and heart rate responses to
N
-methyl-
d
-aspartic acid in the rats with CHF (renal sympathetic nerve activity: 44±2% versus 79±6%;
P
<0.05) compared with CHF-adenovirus vectors encoding the β-galactosidase group. AdnNOS transfection significantly reduced the increased NR
1
receptor mRNA expression (Δ35±5%) and protein levels (Δ24±4%) within the PVN in CHF rats. Furthermore, in neuronal NG-108 cells, NR
1
receptor protein expression decreased in a dose-dependent manner after AdnNOS transfection. According to our results, nNOS downregulation enhances glutamate transmission in the PVN by increasing NR
1
subunit expression. This mechanism may enhance renal sympathetic nerve activity in CHF rats.
A Contribution to Situation Awareness Analysis
Authors: Mundutéguy Christophe , Ragot-Court Isabelle
Published: October 2011

Objective: The aim of the study was to clarify how knowledge elaborated by specific experience may lead to erroneous expectations during interactions between drivers and riders.

Background: Situation awareness is partly determined by prior knowledge. Unshared knowledge may cause difficulties in managing driving interactions, but there is still an important gap in the literature devoted to this field of research.

Method: There were 226 participants, distinguished according to their vehicle use (for drivers, type of vehicle driven and whether they were exclusive or dual drivers; for motorcycle and scooter riders, the type of powered two-wheeler [PTW] used and its engine size) and their driving experience. Focusing on the most vulnerable users, we studied prior representations to interactions using a series of closed questions on drivers’ performance relating to different stages of the interaction process from the perspective both of drivers’ self-reflection and of riders’ expectations.

Results: Although most drivers are self-confident, their abilities tend to be questioned by riders. Owners of medium or large motorbikes feel that drivers do not assess their approach speed accurately. Similarly, scooter riders doubt drivers’ ability to assess the distance that separates them from PTWs. Riders who use medium or large motorbikes are more likely to question drivers’ skills in relation to crossing situations. Scooter riders do so more often for overtaking situations.

Conclusion: The development of shared prior knowledge is essential to prevent accidents and incidents between drivers and riders.

Application: To help improve effectiveness, we re-commend specific ways of embedding each type of road user profile in training, prevention, and research.
Unpacking U.S. Democracy Promotion in Bolivia
Authors: Burron Neil
Published: October 2011

U.S. democracy promotion programs in Bolivia in the early 2000s originally sought to stabilize the neoliberal state through “soft” tactics whose origins were rooted in the “inclusive” neoliberal project of Gonzalo Sánchez de Lozada’s first presidency. As left indigenous social forces tipped the balance of power away from U.S. political allies, these programs were reconfigured to undermine the rise of Evo Morales’s Movement toward Socialism (MAS) through “hard” tactics including support for the right-wing departments of the western part of the country, where autonomist forces mobilized to destabilize the MAS after Morales won the presidential elections in December 2005. U.S. programs also continued to channel support to moderate civil society organizations and nongovernmental organizations that sought to confine the popular revolt within a liberal-institutional framework. Soft and hard tactics combined to promote neoliberal polyarchy.

Estados Unidos buscó promover la democracia en Bolivia durante principios de la década del 2000 para estabilizar al estado neoliberal; sus tácticas “suaves” de promoción democrática partían del proyecto neoliberal “inclusivo” de la primer presidencia de Gonzalo Sánchez de Lozada. Conforme las fuerzas sociales izquierdistas indígenas cobraron poder sobre los aliados de Estados Unidos, estos programas se reconfiguraron para contrarrestar la ascensión del Movimiento al Socialismo (MAS) de Evo Morales. En este caso se utilizaron tácticas “duras” como el apoyo a departamentos derechistas en la parte oeste del país, donde fuerzas autonomistas se movilizaron para desestabilizar al MAS después de que Morales ganara las elecciones de diciembre de 2005. Los programas estadounidenses continuaron canalizando apoyos a organizaciones civiles y no gubernamentales moderadas que buscaron confinar la revuelta popular dentro de un marco liberal e institucional. Las tácticas “suaves” y “duras” se combinaron para promover una poliarquía neoliberal.
Nonviolence and Sustainable Resource Use with External Support
Authors: Gray Vanessa Joan
Published: October 2011

A number of communities in rural Colombia are implementing nonviolence and sustainable resource projects with external support as a means of resisting displacement and dispossession. Practicing peace and rejecting relations with armed groups is a self-protective measure that raises the visibility of the communities’ neutrality and status as noncombatants. Community residents’ strong motivation to continue to live in a specific landscape and maintain small-scale, local-resource-based livelihoods opens potential sources of support beyond the realm of human rights, humanitarian relief, and solidarity organizations to groups interested in protecting traditional cultures and conserving natural landscapes.
BTB Readers' Guide: Social Memory
Authors: Williams Ritva
Published: October 2011

This guide introduces readers to social memory studies as developed by social scientists, and its conceptual relations with history and historiography. It then examines its applications to the study of the Hebrew Bible, New Testament, and Christian origins.
Issues and needs in end-of-life decision making: An international modified Delphi study
Authors: Raijmakers Natasja JH , van Zuylen Lia , Costantini Massimo , Caraceni Augusto , Clark Jean B , De Simone Gustavo , Lundquist Gunilla , Voltz Raymond , Ellershaw John E , van der Heide Agnes
Published: October 2011

Background:

end-of-life decision making is an important aspect of end-of-life care that can have a significant impact on the process of dying and patients’ comfort in the last days of life.

Aim:

the aim of our study was to identify issues and considerations in end-of-life decision making, and needs for more evidence among palliative care experts, across countries and professions.

Participants:

90 palliative care experts from nine countries participated in a modified Delphi study. Participants were asked to identify important issues and considerations in end-of-life decision making and to rate the need for more evidence.

Results:

experts mentioned 219 issues in end-of-life decision making related to the medical domain, 122 issues related to the patient wishes and 92 related to relatives’ wishes, regardless of profession or country ( p > 0.05). In accordance, more than 90% of the experts rated the comfort and wishes of the patient and the potential futility of treatment as important considerations in end-of-life decision making, although some variation was present. When asked about issues that are in need of more evidence, 87% mentioned appropriate indications for using sedatives and effects of artificial hydration at the end of life. A total of 83% mentioned adequate communication approaches.

Conclusions:

palliative care experts from different professions in different countries encounter similar issues in end-of-life decision making. Adequate communication about these issues is universally experienced as a challenge, which might benefit from increased knowledge. This shared experience enables and emphasizes the need for more international research.
Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption
Authors: Wolff Kim , Tsapakis Evangelia M , Pariante Carmine M , Kerwin Robert W , Forsling Mary L , Aitchison Katherine J
Published: October 2011

In this study we investigate the association of cytochrome P450 enzyme CYP2D6, catechol- O-methyl transferase (COMT, Val158Met) and serotonin transporter promoter ( 5-HTTLPR) genotypes on change in cortisol concentration following 3, 4-methylenedioxy-methamphetamine (MDMA, ‘ecstasy’) consumption. Forty-eight subjects (30 males, mean age 23 years), self-nominating regular clubbers provided ‘in the field’ pre- and post-clubbing biological samples and associated information. Of the 39 subjects who provided a post-clubbing urine sample, 21 were positive for MDMA. Plasma cortisol concentrations increased in subjects ( n = 48) tested for cortisol, with changes being significantly greater in the MDMA-positive group (736.9 ± 83.2 vs. 350.9 ± 34.5 mmol/l, p = 0.001). We found a positive association between the low activity COMT genotype (Met/Met) and MDMA-induced change in cortisol and also between this and change in cortisol in the whole sample ( p = 0.039, Bonferroni corrected). For CYP2D6, there was an association between genotype and change in cortisol, confined to subjects with MDMA-positive urine post-clubbing ( p = 0.003, Bonferroni corrected). There was no association with 5-HTTLPR genotype. These associations suggest that chronic use of MDMA may lead to HPA axis dysregulation and that the magnitude of this may be moderated by genetic polymorphism, and warrant further investigation in a larger sample of those who consume the drug on a regular basis.
Effects of amisulpride and aripiprazole on progressive-ratio schedule performance: comparison with clozapine and haloperidol
Authors: den Boon FS , Body S , Hampson CL , Bradshaw CM , Szabadi E , de Bruin N
Published: October 2011

Clozapine and some other atypical antipsychotics (e.g. quetiapine, olanzapine) have been found to exert a characteristic profile of action on operant behaviour maintained by progressive-ratio schedules, as revealed by Killeen’s Mathematical Principles of Reinforcement model of schedule-controlled behaviour. These drugs increase the value of a parameter that expresses the ‘incentive value’ of the reinforcer ( a) and a parameter that is inversely related to the organism’s ‘motor capacity’ (δ). This experiment examined the effects of two further atypical antipsychotics, aripiprazole and amisulpride, on progressive-ratio schedule performance in rats; the effects of clozapine and a conventional antipsychotic, haloperidol, were also examined. In agreement with previous findings, clozapine (4, 8 mg kg−1) increased a and δ, whereas haloperidol (0.05, 0.1 mg kg−1) reduced a and increased δ. Aripiprazole (3,30 mg kg−1) increased δ but did not affect a. Amisulpride (5, 50 mg kg−1) had a delayed and protracted effect: δ was increased 3–6 hours after treatment; a was increased 1.5 hours, and reduced 12–24 hours after treatment. Interpretation based on Killeen’s model suggests that aripiprazole does not share clozapine’s ability to enhance reinforcer value. Amisulpride produced a short-lived enhancement, followed by a long-lasting reduction, of reinforcer value. Both drugs impaired motor performance.
Art Lessons
Authors: Frohnmayer John
Published: October 2011

There’s a difference between being an advocate and a player in the free speech wars. John Frohnmayer reports on how to survive a political ambush
Sketches of Dissent
Authors: Genç Kaya
Published: October 2011

Artists in Turkey may face prosecution and even violence, but the contemporary scene is thriving. Kaya Genç talks to two generations of iconoclasts
Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review
Authors: Sinclair Alexandra J , Kuruvath Sarin , Sen Diptasri , Nightingale Peter G , Burdon Michael A , Flint Graham
Published: October 2011

Background: The role of cerebrospinal fluid (CSF) diversion in treating idiopathic intracranial hypertension (IIH) is disputed.

Method: We conducted a 10-year, retrospective case note review to evaluate the effects of CSF diversion in IIH. Symptoms, signs and details of shunt type, complications and revisions were documented at baseline, 6, 12 and 24 months post-operatively.

Results: Fifty-three IIH patients were shunted [predominantly lumboperitoneal (92%)]. The most common symptom pre-surgery was headache (96%). Post-operatively, significantly fewer patients experienced declining vision and visual acuity improved at 6 ( p = 0.001) and 12 months ( p = 0.016). Headache continued in 68% at 6 months, 77% at 12 months and 79% at 2 years post-operatively. Additionally, post-operative low-pressure headache occurred in 28%. Shunt revision occurred in 51% of patients, with 30% requiring multiple revisions.

Conclusion: We conclude that CSF diversion reduces visual decline and improves visual acuity. Unfortunately, headache remained in the majority of patients and low-pressure headache frequently complicated surgery. Over half of the patients required shunt revision with the majority of these requiring multiple revisions. We suggest that CSF shunting should be conducted as a last resort in those with otherwise untreatable, rapidly declining vision. Alternative treatments, such as weight reduction, may be more effective with less associated morbidity.
Protective properties of five newly synthesized cyclic compounds against sodium azide and N-methyl-N′-nitro-N-nitrosoguanidine genotoxicity
Authors: Turhan Kadir , Ozturkcan S Arda , Turgut Zuhal , Karadayi Mehmet , Gulluce Medine
Published: October 2011

The current study aims to determine the antimutagenic potential of five newly synthesized cyclic compounds against the genotoxic agents sodium azide (NaN3) and N-methyl- N′-nitro- N-nitrosoguanidine (MNNG). The mutant bacterial tester strains were NaN3-sensitive Salmonella typhimurium TA1535 and MNNG-sensitive Escherichia coli WP2 uvrA. According to the results, all the test compounds showed significant antimutagenic activity. The inhibition rates ranged from 26.05% (Compound 4—1 µg/plate) to 68.54% (Compound 5—0.01 µg/plate) for NaN3 and from 32.44% (Compound 3—1 µg/plate) to 60.77% (Compound 5—1 µg/plate) for MNNG genotoxicity. Moreover, the mutagenic potential of the test compounds was investigated using the same strains. The results showed that all the test compounds do not have mutagenic potential on the bacterial strains at the tested concentrations. Thus, the findings of the present study give valuable information about chemical prevention from NaN3 and MNNG genotoxicity.
Long-Term Diffusion Impairment of Cerebral White Matter in a Degenerative Disease of the Central and Peripheral Nervous System
Authors: Blum Katrin Sabine , Hagel Christian , Neuen-Jacob Eva , Herkenrath Peter , Fiehler Jens , Kohlschütter Alfried , Lanfermann Heinrich , Ding Xiao-Qi
Published: October 2011

The authors report an abnormal prolonged restricted magnetic resonance imaging (MRI) proton diffusion that persisted for more than 2 years in a 6.5-year-old boy with a progressive neurological disease characterized by developmental retardation, peripheral polyneuropathy, and bilateral optical nerve atrophy. The long-term restricted magnetic resonance imaging proton diffusion observed in diffusion-weighted magnetic resonance images indicates chronic metabolic tissue impairment in the affected white matter, whereas measurable lactate accumulation in proton magnetic resonance spectroscopy was absent, and no respiratory complex abnormality was found in muscle tissue. These findings are suggestive of a chronically disturbed regulation of energy supply triggering a “slow onset” excitotoxicity, causing chronic hypoxia and leading to slow cell death as has been postulated in certain neurodegenerative processes.
Efficient dynamic analysis of a whole aeroengine using identified nonlinear bearing models
Authors: Groves K H , Bonello P , Hai P M
Published: October 2011

Essential to effective aeroengine design is the rapid simulation of the dynamic performance of a variety of engine and non-linear squeeze-film damper (SFD) bearing configurations. Using recently introduced non-linear solvers combined with non-parametric identification of high-accuracy bearing models it is possible to run full-engine rotordynamic simulations, in both the time and frequency domains, at a fraction of the previous computational cost. Using a novel reduced form of Chebyshev polynomial fits, efficient and accurate identification of the numerical solution to the two-dimensional Reynolds equation (RE) is achieved. The engine analysed is a twin-spool five-SFD engine model provided by a leading manufacturer. Whole-engine simulations obtained using Chebyshev-identified bearing models of the finite difference (FD) solution to the RE are compared with those obtained from the original FD bearing models. For both time and frequency domain analysis, the Chebyshev-identified bearing models are shown to mimic accurately and consistently the simulations obtained from the FD models in under 10 per cent of the computational time. An illustrative parameter study is performed to demonstrate the unparalleled capabilities of the combination of recently developed and novel techniques utilised in this paper.
Control of shroud leakage flows to reduce mixing losses in a shrouded axial turbine
Authors: Gao J , Zheng Q , Yue G , Sun L
Published: October 2011

The losses caused by the leakage flows through the rotor tip clearance, and the mixing losses by the re-entering leakage into the main flow are considerable parts of the total losses in turbines. The main reason for the mixing losses is the different velocity components of main and leakage flows. This leads to shear stresses which cause increased turbulence and losses. This article presents a numerical investigation on three different configurations to control the leakage flows: (a) turning vanes are fixed onto the casing between the fins to turn the shroud leakage flow into the main flow direction in order to reduce the circumferential mixing losses; (b) honeycomb bands are inserted into the casing to weaken the leakage flow in the circumferential direction and reduce the circumferential mixing losses due to the special hexagon structure; and (c) downstream edge of the cavity is chamfered to reduce the radial velocity component of the leakage jet and the separation at the downstream edge, and also to reduce the streamwise mixing losses. A 1.5-stage axial turbine with high-aspect ratio blading was used in this study to investigate the sealing designs as mentioned. The flow simulation results of the three configurations were analysed and compared in this article.
Development of a comprehensive and flexible forward dynamic powertrain simulation tool for various hybrid electric vehicle architectures
Authors: Cheng C , McGordon A , Jones R P , Jennings P A
Published: October 2011

This paper presents a comprehensive and flexible forward dynamic powertrain simulation tool, WARwick Powertrain Simulation Tool for ARchitectures 2 (WARPSTAR2), for modelling of conventional internal combustion engine, hybrid, and pure electric vehicles. WARPSTAR2 includes physical powertrain component models and their controllers, a hybrid supervisory controller, the driver, and the environment model. The physical powertrain component models are developed in Dymola, while the component controllers, the hybrid supervisory controllers, and the driver model are realized in MATLAB/Simulink. Thus the power of these two software tools is combined.

A generalized fuzzy-logic-based supervisory controller is proposed for all hybrid electric vehicle (HEV) architectures so that all HEVs with different architectures share the same structure of supervisory controller. The generalized formation can be used for the supervisory controllers of different HEV architectures with varied parameter settings, thus facilitating the controller design process. The rule-based supervisory controller is also developed in WARPSTAR2. Simulation is carried out for different HEVs with these two supervisory controllers in the driving cycles. The results of engine and battery power usages with these two supervisory controllers are similar and the differences of predicted engine fuel consumptions between the two supervisory controllers are within 5 per cent.
Collaborate With Practitioners
Authors: Kieser Alfred , Leiner Lars
Published: October 2011

Collaborative research is seen as a promising approach for bridging the rigor-relevance gap. In this essay, the authors criticize that the proponents of this approach tend to downplay communication difficulties between practitioners and researchers. The authors apply psycholinguistic concepts of layperson–expert communication and system theory to demonstrate that it is extremely difficult to integrate knowledge that has been generated in the different contexts of science and practice. The authors argue that collaborative approaches like action research, consulting, or executive training are more effective than collaborative research in ridging the rigor-relevance gap. A critical review of reports on collaborative research projects discloses some evidence in support of their assumptions. We conclude by encouraging researchers and practitioners to inspire each other through different forms of collaboration. However, we argue that attempts to turn managers into coresearchers with the special responsibility for making sure that rigor is complemented by relevance are overvalued in the academic discourse.
Tau protein: a possible prognostic factor in optic neuritis and multiple sclerosis
Authors: Frederiksen J , Kristensen K , Bahl JMC , Christiansen M
Published: October 2011

Background: Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk of progression from ON to MS.

Objective: To investigate the association between tau protein concentration and 14-3-3 protein in the cerebrospinal fluid (CSF) of patients with monosymptomatic optic neuritis (ON) versus patients with monosymptomatic onset who progressed to multiple sclerosis (MS). To evaluate results against data found in a complete literature review.

Methods: A total of 66 patients with MS and/or ON from the Department of Neurology of Glostrup Hospital, University of Copenhagen, Denmark, were included. CSF samples were analysed for tau protein and 14-3-3 protein, and clinical and paraclinical information was obtained from medical records.

Results: The study shows a significantly increased concentration of tau protein in CSF from patients with relapsing–remitting MS and patients monosymptomatic at onset who progressed to MS, but interestingly no increased tau protein concentration in monosymptomatic ON. The concentration of tau protein was significantly correlated to Expanded Disability Status Scale score. No 14-3-3 protein was detected in any CSF sample.

Conclusions: The results of this study invite further exploration of the possible role of tau protein as a prognostic factor to predict progression from ON to MS in future studies.
Carotid stent fracture and restenosis management
Authors: Hynes Brian G , Ruggiero Nicholas J , Hirsch Joshua A , Rosenfield Kenneth
Published: October 2011

We report an unusual case of asymptomatic accelerated right carotid artery in-stent restenosis in a patient referred for revascularization of a de novo stenosis of her left internal carotid artery.
The prescription of oral contraceptives and its relation to the incidence of chlamydia and abortion in Sweden 1997–2005
Authors: Halvarsson Veronika , Ström Sara , Liljeros Fredrik
Published: October 2011

Aims: The aim of this study is to examine the association between the prescription of oral contraceptives and the incidence of chlamydia, and between the prescription of oral contraceptives and the number of abortions in a population-based ecological study. Methods: For this study we used register data from the Swedish Institute for Infectious Disease Control (chlamydia incidence), the Swedish National Board of Health and Welfare (number of abortions), Statistics Sweden (population data), and Apoteket (Swedish pharmacy) (prescriptions for oral contraceptives). We conducted ordinary least squares regression analysis of the association between chlamydia or abortions and the prescription of oral contraceptives. Results: The prescription of oral contraceptives has a positive association on both the incidence of chlamydia and the numbers of abortion. Our best model predicts that prescription of 100 yearly doses of oral contraceptives increase the abortions by 3.3 cases among 16-year-old women and 0.7 cases among 29-year-old women, while cases of chlamydia increase by 6.7 among 16-year-old women and 1.5 among 29-year-old women. Conclusions: Our findings indicate that the use of oral contraceptives among young people and young adults is positively associated with the chlamydia incidence and the abortion rate in these populations in Sweden.
Identifying fast-food restaurants using a central register as a measure of the food environment
Authors: Toft Ulla , Erbs-Maibing Peter , Glümer Charlotte
Published: October 2011

Objective: To validate the identification and location of fast-food restaurants according to a government list of inspected food stores and restaurants. Methods: Fast-food restaurants in the Capital Region of Denmark were identified using a government list of inspected food stores and restaurants (the Smiley register, spring 2010). Ground-truthing was used as the validation method and was performed in May and June 2010 in 125 randomly selected 250 × 250 m grid cells. Results: A total of 186 fast-food restaurants was identified by ground-truthing and 99% of these were registered in the same grid cell by the Smiley register. However, only 152 restaurants of these were categorised as fast-food restaurants by both methods. The sensitivity was 82% and the positive predictive value was 92%. The mean ± standard deviation position accuracy was 15 ± 24 m. Conclusions: Using a government list of inspected restaurants was found to be a valid and useful alternative to expensive and time-consuming field observation and provided a relatively accurate tool for identifying and locating fast-food restaurants in communities.
Association between hand grip/body weight ratio and disability pension due to musculoskeletal disorders: A population-based cohort study of 1 million Swedish men
Authors: Ropponen Annina , Silventoinen Karri , Tynelius Per , Rasmussen Finn
Published: October 2011

Aims: To investigate the predictive value of hand grip/body weight ratio and hand grip strength in early adulthood for obtaining a disability pension (DP) due to musculoskeletal disorders in later life. Methods: A nationwide population-based sample of men born 1951–76 ( n = 1,387,166) in Sweden and anthropometric and strength indicators from their conscription examination. Register data on the date and diagnoses of granted DP between the years 1971–2006. Cox proportional hazards regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). Results: The lowest quintile of hand grip/body weight ratio predicted a greatly increased risk (HR 2.51, 95% CI 2.40–2.63) for DP due to musculoskeletal disorders compared to the mid-quintile. The highest quintile of hand grip/body weight ratio predicted a decreased risk (HR 0.80, 95% CI 0.75–0.84). Stratification of the hand grip/body weight ratio with body mass index confirmed the results. However, the highest quintiles of hand grip strength adjusted for height and weight predicted a somewhat increased risk for DP due to musculoskeletal disorders (HR 1.25, 95% CI 1.18–1.32). Conclusions: This study indicates that the hand grip/body weight ratio in young adulthood is strongly and inversely associated with men's risk of obtaining a disability pension due to musculoskeletal disorders in later life. However, the risk seems to be mediated through the body weight. The properties of hand grip/body weight ratio should be further evaluated before it can be recommended for use in clinical and epidemiological studies.
Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia
Authors: Hijiya Nobuko , Thomson Blythe , Isakoff Michael S. , Silverman Lewis B. , Steinherz Peter G. , Borowitz Michael J. , Kadota Richard , Cooper Todd , Shen Violet , Dahl Gary , Thottassery Jaideep V. , Jeha Sima , Maloney Kelly , Paul Jo-Anne , Barry Elly , Carroll William L. , Gaynon Paul S.
Published: October 2011

The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.
Conditional Probability of Survival in Patients With Newly Diagnosed Glioblastoma
Authors: Polley Mei-Yin C. , Lamborn Kathleen R. , Chang Susan M. , Butowski Nicholas , Clarke Jennifer L. , Prados Michael
Published: October 2011

Purpose

The disease outcome for patients with cancer is typically described in terms of estimated survival from diagnosis. Conditional probability offers more relevant information regarding survival for patients once they have survived for some time. We report conditional survival probabilities on the basis of 498 patients with glioblastoma multiforme receiving radiation and chemotherapy. For 1-year survivors, we evaluated variables that may inform subsequent survival. Motivated by the trend in data, we also evaluated the assumption of constant hazard.

Patients and Methods

Patients enrolled onto seven phase II protocols between 1975 and 2007 were included. Conditional survival probabilities and 95% CIs were calculated. The Cox proportional hazards model was used to evaluate prognostic values of age, Karnofsky performance score (KPS), and prior progression 1-year post diagnosis. To assess the constant hazard assumption, we used a likelihood-ratio test to compare the Weibull and exponential distributions.

Results

The probabilities of surviving an additional year given survival to 1, 2, 3, and 4 years were 35%, 49%, 69%, and 93%, respectively. For patients who survived for 1 year, lower KPS and progression were significantly predictive of shorter survival (both P < .001), but age was not (hazard ratio, 1.22 for a 10-year increase; P = .25). The Weibull distribution fits the data significantly better than exponential (P = .02), suggesting nonconstant hazard.

Conclusion

Conditional probabilities provide encouraging information regarding life expectancy to survivors of glioblastoma multiforme. Our data also showed that the constant hazard assumption may be violated in modern brain tumor trials. For single-arm trials, we advise using individual patient data from historical data sets for efficacy comparisons.
Alternative End Points to Evaluate a Therapeutic Strategy in Advanced Colorectal Cancer: Evaluation of Progression-Free Survival, Duration of Disease Control, and Time to Failure of Strategy—An Aide et Recherche en Cancérologie Digestive Group Study
Authors: Chibaudel Benoist , Bonnetain Franck , Shi Qian , Buyse Marc , Tournigand Christophe , Sargent Daniel J. , Allegra Carmen J. , Goldberg Richard M. , de Gramont Aimery
Published: October 2011

Purpose

Progression-free survival (PFS) is not an optimal end point to evaluate therapeutic strategies in advanced colorectal cancer (ACRC). Therefore, composite end points have been proposed to evaluate a chemotherapy strategy when sequential treatments are available: duration of disease control (DDC) and time to failure of strategy (TFS). The goal of this study was to evaluate these alternative end points and their potential surrogacy for overall survival (OS).

Methods

We pooled individual patient data from three randomized trials evaluating chemotherapy strategy, which accrued 1,042 patients with previously untreated ACRC. In these trials, first-line treatment was either oxaliplatin- or irinotecan-based chemotherapy. Compared with TFS, DDC included neither time interval between progression and next sequence of treatment nor time to progression if the best result of the next sequence of treatment was progression.

Results

There was good correlation between DDC and OS (correlation of median: r, 0.62; correlation of hazard ratio [HR]: adjusted copula R2, 0.72) and between TFS and OS (correlation of median: r, 0.59; correlation of HR: adjusted copula R2, 0.67). There was no correlation between PFS and OS (correlation of median: r, 0.45; correlation of HR: adjusted copula R2, 0.47).

Conclusion

DDC and TFS roughly achieved the same results. Both are acceptable new end points to evaluate a therapeutic strategy in ACRC. Although TFS achieved a pragmatic evaluation of a multiline strategy, DDC captured the effect of a specific sequence in a therapeutic strategy.
Controlling the Lungs Via the Brain: A Novel Neurosurgical Method to Improve Lung Function in Humans
Authors: Hyam Jonathan A. , Brittain John-Stuart , Paterson David J. , Davies Robert J. O. , Aziz Tipu Z. , Green Alexander L.
Published: October 2011

BACKGROUND:

Deep brain stimulation (DBS) of subcortical brain areas such as the periaqueductal grey and subthalamic nucleus has been shown to alter cardiovascular autonomic performance. The supramedullary circuitry controlling respiratory airways is not well defined and has not been tested in humans.

OBJECTIVE:

To use direct electric stimulation via DBS macroelectrodes to test whether airway resistance could be manipulated by these areas in awake humans.

METHODS:

Thirty-seven patients with in-dwelling deep brain electrodes for movement disorders or chronic pain underwent spirometry according to the European Respiratory Society guidelines. Testing was performed randomly 3 times on stimulation and 3 times off stimulation; patients were blinded to the test. Thoracic diameter changes were measured by a circumferential pressure-sensitive thoracic band. Ten periaqueductal grey and 10 subthalamic nucleus patients were tested. To control for confounding pain and movement disorder relief, the sensory thalamus in 7 patients and globus pallidus interna in 10 patients, respectively, were also tested.

RESULTS:

Peak expiratory flow rate (PEFR) increased significantly with periaqueductal grey and subthalamic nucleus stimulation by up to 14% (P = .02 and .005, respectively, paired-samples Student t tests). Stimulation of control nuclei produced no significant PEFR change. Similarly, changes in thoracic diameter reflecting skeletal activity rather than airway caliber did not correlate with the improvement in PEFR. Forced expiratory volume in 1 second was unchanged by stimulation.

CONCLUSION:

DBS can improve PEFR in chronic pain and movement disorder patients. This finding provides insights into the neural modulation of respiratory performance and may explain some of the subjective benefits of DBS.
A Novel Scoring System for Assessing Chiari Malformation Type I Treatment Outcomes
Authors: Aliaga Leonardo , Hekman Katherine E. , Yassari Reza , Straus David , Luther Gaurav , Chen Judy , Sampat Ajay , Frim David
Published: October 2011

Background:

Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.

Objective:

We developed a novel scoring system and applied it retrospectively to 146 patients treated at our institution in order to create and verify a simple and quantifiable assessment of Chiari outcomes.

Methods:

The Chicago Chiari Outcome Scale (CCOS) uses 4 postoperative outcome categories (pain, nonpain symptoms, functionality, and complications) graded 1 to 4 for a total possible score of 16. As a comparison with current Chiari outcome methodology, each patient was also placed into a gestalt outcome group of “improved,” “unchanged,” or “worse” (I/U/W). Patients were stratified by CCOS scores and by I/U/W group.

Results:

Stratifying patients by total CCOS scores showed that patients who achieved CCOS scores between 13 and 16 were predominantly in the I/U/W improved group (n = 101, 69%); scores between 9 and 12 were predominantly I/U/W unchanged (n = 39, 27%), and scores between 4 and 8 were I/U/W worse (n = 6, 4%). Symptom subscore results provided insight into the specifics of the overall outcome in addition to the more quantitative nature of the 16-point scale.

Conclusion:

We describe a CCOS that assigns higher scores to patients judged improved by gestalt I/U/W ratings and lower scores to those who were unchanged or worse while defining outcome in 4 specific subcategories. As such, this CCOS should allow for a more unified and quantifiable outcome assessment after Chiari surgery.
Deep Brain Stimulation in Area LC Controllably Triggers Auditory Phantom Percepts
Authors: Larson Paul S. , Cheung Steven W.
Published: October 2011

BACKGROUND:

Tinnitus is predominantly viewed as the consequence of dysfunctional hyperactivity, plastic change, or synchronized oscillations in the central auditory system. An alternative to the current auditory-centric view of auditory phantom perception is the basal ganglia-centric view. Recent electrical stimulation experiments in area LC, a locus of the caudate nucleus positioned at its anterior body, has shown loudness modulation of existing tinnitus percepts.

OBJECTIVE:

To demonstrate that auditory phantoms are gated by the dorsal striatum.

METHODS:

Electrical stimulation in area LC via a deep brain stimulation lead was performed in 6 interactive adult subjects (3 with and 3 without chronic tinnitus) undergoing surgery to treat movement disorders. Tinnitus loudness was rated on a 0 to 10 scale, sound quality was described, and localization was referenced to 1 or both ears.

RESULTS:

Short-term area LC stimulation triggered new phantom tones, clicks, and frequency modulated sounds in 5 subjects and altered sound quality of an existing tinnitus percept in 1 subject. The results of this study indicate that perceptual awareness of auditory phantoms is contingent on satisfying a permission condition controlled by the dorsal striatum. Potential auditory phantoms are not automatically gated to reach perceptual awareness. A phantom percept gate control model is proposed.

CONCLUSION:

Neuromodulation of area LC can trigger temporary gate dysfunction and reversibly release new phantoms for conscious awareness. Restoration of restrictive dorsal striatal gate function to treat problematic phantom percepts may be realized by adopting long-term area LC neuromodulation and choosing optimal stimulation parameters.