bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of splenic marginal zone lymphoma of the CNS with high-dose therapy and allogeneic stem cell transplantation
Authors: Busemann Christoph , Gudzuhn Andrej , Hirt Carsten , Kirsch Michael , Vogelgesang Silke , Schmidt Christian A , Dölken Gottfried , Krüger William H
Published: October 2012

Therapy of indolent lymphomas with involvement of the central nervous system (CNS) has not been standardized so far. A 42-year old male patient presented with neurological signs because of leukemic splenic marginal zone lymphoma (SMZL) manifested in bone marrow, lymph nodes and CNS. Due to the aggressiveness of the disease and the young age of the patient, an intensive immunochemotherapy followed by high-dose therapy with busulfan, thiotepa and fludarabine and subsequent unrelated allogeneic stem cell transplantation (alloSCT) was performed. The haemopoietic stem cells engrafted in time and the patient is doing well (ECOG 0) without evidence for active lymphoma three years after transplantation. Highly sensitive tests by specific quantitative real-time polymerase chain reaction for presence of lymphoma cells in blood and bone marrow indicated also a molecular remission. The reported case shows the feasibility of high-dose therapy and allogeneic stem cell transplantation in high-risk patients with CNS-involvement of indolent non-Hodgkin’s lymphoma. In addition, the case supports the hypothesis that the graft-versus lymphoma effect after alloSCT is also active within the CNS.
Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood–brain barriers studied with (R)-[11C]verapamil positron emission tomography
Authors: Müllauer Julia , Kuntner Claudia , Bauer Martin , Bankstahl Jens P , Müller Markus , Voskuyl Rob A , Langer Oliver , Syvänen Stina
Published: October 2012

Background

This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET).

Methods

Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Q
in and Q
out) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood–brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (V
T-NLME) was calculated.

Results

Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Q
out. The reduction in Q
out in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Q
out in humans was apparent during and immediately after tariquidar administration (twofold reduction in Q
out) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment V
br1. Tariquidar treatment lead to an increase in V
T-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment.

Conclusions

Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans.
Late pharmacologic conditioning with volatile anesthetics after cardiac surgery
Authors: Steurer Marc P , Steurer Martina A , Baulig Werner , Piegeler Tobias , Schläpfer Martin , Spahn Donat R , Falk Volkmar , Dreessen Pamela , Theusinger Oliver M , Schmid Edith R , Schwartz David , Neff Thomas A , Beck-Schimmer Beatrice
Published: October 2012

Introduction

The aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.

Methods

Anesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.

Results

Fifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).

Conclusions

The data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.

Trial registration

ClinicalTrials.gov: NCT00924222.
Complication rates as a trauma care performance indicator: a systematic review
Authors: Moore Lynne , Stelfox Henry Thomas , Turgeon Alexis F
Published: October 2012

Introduction

Information on complication rates is essential to trauma quality improvement efforts. However, it is unclear which complications are the most clinically relevant. The objective of this study was to evaluate whether there is consensus on the complications that should be used to evaluate the performance of acute care trauma hospitals.

Methods

We searched the Medline, EMBASE, Cochrane Central, CINAHL, BIOSIS, TRIP and ProQuest databases and included studies using at least one nonfatal outcome to evaluate the performance of acute care trauma hospitals. Data were extracted in duplicate using a piloted electronic data abstraction form. Consensus was considered to be reached if a specific complication was used in ≥ 70% of studies (strong recommendation) or in ≥ 50% of studies (weak recommendation).

Results

Of 14,521 citations identified, 22 were eligible for inclusion. We observed important heterogeneity in the complications used to evaluate trauma care. Seventy-nine specific complications were identified but none were used in ≥ 70% of studies and only three (pulmonary embolism, deep vein thrombosis, and pneumonia) were used in ≥ 50% of studies. Only one study provided evidence for the clinical relevance of complications used and only five studies (23%) were considered of high methodological quality.

Conclusion

Based on the results of this review, we can make a weak recommendation on three complications that should be used to evaluate acute care trauma hospitals; pulmonary embolism, deep vein thrombosis, and pneumonia. However, considering the observed disparity in definitions, the lack of clinical justification for the complications used, and the low methodological quality of studies, further research is needed to develop a valid and reliable performance indicator based on complications that can be used to improve the quality and efficiency of trauma care.
Probability of Metachronous Testicular Cancer in Patients With Biopsy-Proven Intratubular Germ Cell Neoplasia Depends on First-Time Treatment of Germ Cell Cancer
Authors: Brabrand Sigmund , Fosså Sophie D. , Cvancarova Milada , Axcrona Ulrika , Lehne Gustav
Published: October 2012

Purpose

To evaluate the probability of subsequent testicular cancer (STC) in patients with intratubular germ cell neoplasia unclassified (IGCNU) treated for first-time invasive germ cell cancer.

Patients and Methods

Sixty-one patients with germ cell testicular cancer or extragonadal germ cell cancer received follow-up from diagnosis of IGCNU to development of STC, initiation of IGCNU-definitive treatment (orchiectomy/radiotherapy), emigration, death, or end of follow-up. The probability of STC was assessed in subgroups according to chemotherapy burden.

Results

The probability of STC in the nonexposed patients was significantly increased compared with those exposed to chemotherapy (P = .05; 5-year probability of 54% [95% CI, 33% to 78%] and 23% [95% CI, 11% to 45%], respectively). In the group of patients treated with one to three cycles or no chemotherapy, the probability of STC was significantly increased compared with those exposed to four or more cycles (P = .03; 5-year probability of 42% [95% CI, 27% to 62%] and 22% [95% CI, 8% to 54%], respectively). Twenty-two of 22 patients were tumor-free and alive at a median of 56 months (range, 2 to 184 months) after diagnosis of STC.

Conclusion

Platinum-based chemotherapy may reduce the probability of STC in patients with IGCNU, particularly in those treated with four or more cycles of chemotherapy. A watch-and-wait strategy for patients with IGCNU may be justified in selected patients with future plans for paternity.
Role of Comparative Effectiveness Research in Cancer Funding Decisions in Ontario, Canada
Authors: Hoch Jeffrey S. , Hodgson David C. , Earle Craig C.
Published: October 2012

Recently, the evidence-based drug funding process in Ontario, Canada, was challenged by a young mother with a breast tumor too small, based on the evidence that existed at the time, to qualify for an expensive drug. In reality, this is only the latest in a number of challenges the publicly funded health care system has had to deal with in the face of an evolving drug policy landscape. This article defines comparative effectiveness research (CER), considering how it is viewed differently in the United States and Canada. It also reviews the role CER now plays in the Ontario drug funding process and concludes with a review of the challenges and opportunities of using observational data to conduct CER and incorporate it into policy making within a universal health care system. Many of the issues faced by Ontario are relevant beyond Canada, including in the United States during this period of health care reform.
Randomized Controlled Trials and Comparative Effectiveness Research
Authors: Hahn Olwen M. , Schilsky Richard L.
Published: October 2012

Comparative effectiveness research (CER) has been promoted as a way to improve the translation gap between clinical research and everyday clinical practice as well as to deliver more cost-effective health care. CER will account for a significant portion of funding allocated by the US government for health care research. Oncology has a rich history of improving clinical outcomes and advancing research through randomized controlled trials (RCTs). In this article, we review the role of RCTs in achieving the goals of CER, with particular emphasis on the role of publicly funded clinical trials.
Using Health Technology Assessment to Identify Gaps in Evidence and Inform Study Design for Comparative Effectiveness Research
Authors: Tunis Sean R. , Turkelson Charles
Published: October 2012

Health technology assessment (HTA) is primarily used as a tool to ensure that clinical and policy decisions are made with the benefit of a systematic analysis of all completed research. This article describes the progress and potential for HTA reports to improve the quality and relevance of future research and to better serve the information needs of patients, clinicians, payers, and other decision makers. We conducted a review of the current published literature and working papers describing past, ongoing, and future initiatives that rely on HTA reports to identify gaps in evidence and improve the design of future research. Although still in a developmental stage, significant progress is under way to improve methods for using HTA reports for the systematic identification of research gaps, prioritization of future research, and improvement of study designs. Several well-defined frameworks have been developed to assist those who produce HTA to become more effective in these additional domains of work. A recurring element of this work is the importance of meaningfully involving stakeholders in the process of defining future research needs and designing studies to address them. Patients, clinicians, and payers are important audiences for completed research and are now recognized as serving an important role in determining what future research is needed. There are substantial opportunities to improve the quality, relevance, and efficiency of clinical research. Recent efforts are beginning to demonstrate the potential to build on the work invested in developing HTA reports to provide a roadmap toward these objectives.
Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors
Authors: Merchant Melinda S. , Geller James I. , Baird Kristin , Chou Alexander J. , Galli Susana , Charles Ava , Amaoko Martha , Rhee Eunice H. , Price Anita , Wexler Leonard H. , Meyers Paul A. , Widemann Brigitte C. , Tsokos Maria , Mackall Crystal L.
Published: October 2012

Purpose

Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor–related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors.

Patients and Methods

This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age ≤ 21 years with recurrent or progressive solid tumors.

Results

Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response.

Conclusion

Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.
TNF-α Up-Regulates Protein Level and Cell Surface Expression of the Leptin Receptor by Stimulating Its Export via a PKC-Dependent Mechanism
Authors: Gan Lixia , Guo Kaiying , Cremona Maria Laura , McGraw Timothy E. , Leibel Rudolph L. , Zhang Yiying
Published: October 2012

Increasing evidence suggests that inflammation/cytokines may modulate hypothalamic responses to leptin, which is a key regulator of energy homeostasis and inflammatory/stress responses. We investigated a possible role of TNF-α, a key early mediator of inflammation, in regulating the expression and trafficking of the long-isoform leptin receptor (LEPRb), the primary mediator of leptin signaling, in cultured cells. We found that TNF-α in a wide range of concentrations up-regulated LEPRb protein level and soluble LEPR (sLEPR) release via ectodomain shedding of LEPRb in multiple cell types, including neuronal cells. TNF-α also acutely increased LEPRb cell surface expression and leptin-induced STAT3 phosphorylation. In contrast, TNF-α had no significant effects on the protein level or cell surface expression of several other transmembrane proteins, including the transferrin receptor and cadherin. The stimulatory effects of TNF-α on LEPRb cell surface expression and sLEPR release were not dependent on de novo protein synthesis or functional lysosomes but were blocked by brefeldin A, suggesting that an intact Golgi or continuous endoplasmic reticulum to Golgi transport of newly synthesized proteins is required for these effects. However, TNF-α did not increase the half-life of cell surface LEPRb. Protein kinase C (PKC) inhibitor GF109203X abrogated the effects of TNF-α, whereas the pan-PKC activator phorbol 12-myristate 13-acetate mimicked the TNF-α effects. Taken together, our results suggest that TNF-α, via activation of PKC, regulates anterograde trafficking and/or degradation of LEPRb in the biosynthetic pathway, leading to concomitant increases in LEPRb protein level, cell surface expression, and sLEPR production. The finding that LEPRb cell surface expression and sLEPR production, key modulators of leptin sensitivity and bioavailability, are direct targets of TNF-α signaling could have a potentially important implication in the regulation of leptin signaling activity in different pathophysiological conditions as diverse as obesity and sepsis.
Large Conductance Ca2+-Activated and Voltage-Activated K+ Channels Contribute to the Rise and Maintenance of Estrogen-Induced Uterine Vasodilation and Maintenance of Blood Pressure
Authors: Rosenfeld Charles R. , Roy Timothy
Published: October 2012

Uterine blood flow (UBF) increases greater than 4-fold 90 min after systemic estradiol-17β (E2β) in nonpregnant sheep and remains elevated longer than 6–8 h; mean arterial pressure (MAP) is unchanged. Large-conductance Ca+2-activated (BKCa) and voltage-activated (KV) K+ channels contribute to the acute rise in UBF; their role in maintaining UBF and MAP longer than 90 min is unknown. We examined this in five nonpregnant, ovariectomized ewes with uterine artery (UA) flow probes and catheters in a UA for infusion of K+ channel inhibitors and uterine vein to sample venous effluent. Animals received systemic E2β (1.0 μg/kg; control), E2β+UA tetraethylammonium (TEA; 0.4–0.8 mm, n = 4), and E2β+UA 4-aminopyridine (4-AP; 0.01–0.08 mm, n = 4) to block BKCa and KV, respectively, while monitoring MAP, heart rate, and UBF. Uterine cGMP synthesis was measured. Ninety minutes after E2β, UBF rose 4.5-fold, uterine vascular resistance (UVR) fell greater than 5-fold and MAP was unchanged [78 ± 0.8 (sem) vs. 77 ± 1.5 mm Hg] in control studies and before UA inhibition with TEA and 4-AP. Between 90 and 120min, UBF, UVR, and MAP were unchanged after E2β alone. E2β+TEA dose dependently decreased ipsilateral UBF and increased UVR (24 ± 8.9 and 38 ± 16%, respectively, at 0.8 mm; P < 0.03); MAP was unchanged. Contralateral UBF/UVR were unaffected. E2β+4-AP also dose dependently decreased ipsilateral UBF and increased UVR (27 ± 5.3 and 76 ± 18%, respectively, at 0.08 mm; P < 0.001); however, MAP rose 27 ± 6.9% (P ≤ 0.006). E2β increased uterine cGMP synthesis greater than 3.5-fold and was unaffected by local K+ channel inhibition. BKCa and KV contribute to the rise and maintenance of E2β-induced uterine vasodilation, which is partially cGMP dependent. Systemic vascular KV also contributes to maintaining MAP after systemic E2β.
An Approach to Pyrazoline-Fused Chlorins by Dipolar [3 + 2]-Cycloaddition of Iminonitriles to meso-Tetrakis(pentafluorophenyl)porphyrin: Synthesis of New PDT Photosensitizers
Authors: Wyrebek Przemysaw , Ostrowski Stanisaw
Published: October 2012

meso-Tetrakis(pentafluorophenyl)porphyrin reacts at higher temperature with unstable iminonitriles (R–C≡N+–N−–Ar), affording pyrazoline-fused chlorins, according to dipolar [3 + 2]-cycloaddition pathway. The respective iminonitriles were in situ generated from the corresponding functionalized α-halogenohydrazine derivatives by 1,3-elimination of HX in the presence of base (NEt3, DABCO). This method allows synthesis of very attractive moieties which may be of potential use as sensitizers in photodynamic therapy (PDT).
Novel mutations in the Dubin–Johnson syndrome gene ABCC2/MRP2 and associated biochemical changes
Authors: Devgun Manjit S , El-Nujumi Adil M , O'Dowd Geraldine J , Barbu Véronique , Poupon Raoul
Published: October 2012

A patient with sepsis and jaundice was admitted for diagnosis and treatment. Associated biochemical changes included increased C-reactive protein, conjugated bilirubin and gamma-glutamyltransferase, the duration of which was protracted. High urine coproporphyrin isomer-1 and immunostaining of liver tissue suggested Dubin–Johnson syndrome. DNA sequencing using polymerase chain reaction amplification of the ABCC2 gene revealed the patient to have a compound heterozygous variant of MRP2, a molecule involved in canalicular transport of bilirubin. There was a history of jaundice since infancy.
Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma
Authors: Eisenhofer Graeme , Lattke Peter , Herberg Maria , Siegert Gabriele , Qin Nan , Därr Roland , Hoyer Jana , Villringer Arno , Prejbisz Aleksander , Januszewicz Andrzej , Remaley Alan , Martucci Victoria , Pacak Karel , Ross H Alec , Sweep Fred C G J , Lenders Jacques W M
Published: October 2012

Background

Measurements of plasma normetanephrine and metanephrine provide a useful diagnostic test for phaeochro-mocytoma, but this depends on appropriate reference intervals. Upper cut-offs set too high compromise diagnostic sensitivity, whereas set too low, false-positives are a problem. This study aimed to establish optimal reference intervals for plasma normetanephrine and metanephrine.

Methods

Blood samples were collected in the supine position from 1226 subjects, aged 5-84 y, including 116 children, 575 normotensive and hypertensive adults and 535 patients in whom phaeochromocytoma was ruled out. Reference intervals were examined according to age and gender. Various models were examined to optimize upper cut-offs according to estimates of diagnostic sensitivity and specificity in a separate validation group of 3888 patients tested for phaeochromocytoma, including 558 with confirmed disease.

Results

Plasma metanephrine, but not normetanephrine, was higher (P < 0.001) in men than in women, but reference intervals did not differ. Age showed a positive relationship (P < 0.0001) with plasma normetanephrine and a weaker relationship (P = 0.021) with metanephrine. Upper cut-offs of reference intervals for normetanephrine increased from 0.47 nmol/L in children to 1.05 nmol/L in subjects over 60 y. A curvilinear model for age-adjusted compared with fixed upper cut-offs for normetanephrine, together with a higher cut-off for metanephrine (0.45 versus 0.32 nmol/L), resulted in a substantial gain in diagnostic specificity from 88.3% to 96.0% with minimal loss in diagnostic sensitivity from 93.9% to 93.6%.

Conclusions

These data establish age-adjusted cut-offs of reference intervals for plasma normetanephrine and optimized cut-offs for metanephrine useful for minimizing false-positive results.
Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery
Authors: Patle R , Dubb S , Alaghband-Zadeh J , Sherwood R A , Tam F , Frankel A , Moniz C , Bueter M , Vincent R P , le Roux C W
Published: October 2012

Background

Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery.

Methods

Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery.

Results

Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg ( P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg ( P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 μmol/L ( P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 μmol/L ( P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant ( P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO.

Conclusions

After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO–ADMA axis. Other causes for the changes in BP should therefore be considered.
A Seminar for Solving Client Problems in Project Teams
Authors: Salo Ahti
Published: October 2012

We describe the course “Seminar on Case Studies in Operations Research” in which teams of four or five students work on real problems posed by firms and governmental research institutions. In this course, which is taught at Aalto University School of Science, students use operations research to solve these problems and also develop teamwork, communication, and project management skills. Since 2001, the student teams have carried out more than 60 projects of which many have had significant business and societal impacts. We discuss experiences from this course and consider implementation details that have contributed to the attainment of learning objectives.
Bi-Objective Bus Routing: An Application to School Buses in Rural Areas
Authors: Pacheco Joaquín , Caballero Rafael , Laguna Manuel , Molina Julián
Published: October 2012

The min-max vehicle routing problem (VRP) is a variant of the classical VRP in which the objective is to minimize the duration of the longest route. Examination of the VRP literature indicates that the min-max VRP has received less attention than other variants have over the years. However, the problem has important practical applications, such as those related to routing school buses. In this setting, in addition to the min-max criterion imposed on the time it takes to complete the longest route, school districts are concerned with the minimization of the total distance traveled, which is the objective of the classical VRP. Hence, the problem is formulated as a bi-objective optimization model that trades off service (i.e., the minimization of the longest route) and operational cost (i.e., the minimization of the total distance traveled). We develop a solution procedure for this problem by applying tabu search within the framework of Multiobjective Adaptive Memory Programming and compare it to an implementation of the Non-dominated Sorting Genetic Algorithm—a well-known approach to multiobjective optimization. We also assess the merit of the solution method by comparing our approximations with solution frontiers obtained with an ε-constraint implementation.
Determining the Number of Airport Arrival Slots
Authors: Churchill Andrew M. , Lovell David J. , Mukherjee Avijit , Ball Michael O.
Published: October 2012

At many congested airports, access rights are governed by a system of slot controls. A slot conveys to its owner the right to schedule an operation (flight arrival or departure). In this paper, stochastic optimization models are developed to determine the numbers of slots to make available over the course of a day, controlling for the long-term uncertainty induced in arrival or departure capacities because of weather conditions. Three related integer programming formulations for this problem are presented, which vary both in their computational properties and the economic trade-offs modeled. The models are compared both analytically and computationally. Experiments using data from New York's LaGaurdia Airport are reported to demonstrate the impact of these models on optimizing slot profiles while considering long-term capacity uncertainty and several policy objectives.
Determining Stochastic Airspace Capacity for Air Traffic Flow Management
Authors: Clarke John-Paul B. , Solak Senay , Ren Liling , Vela Adan E.
Published: October 2012

Deterministic air traffic flow management (TFM) decisions—the state of the art in terms of implementation—often result in unused airspace capacity. This is because the inherent uncertainties in weather predictions make it difficult to determine the number of aircraft that can be safely accommodated in a region of airspace during a given period. On the other hand, stochastic TFM algorithms are not amenable to implementation in practice due to the lack of valid stochastic mappings between weather forecasts and airspace capacity to serve as inputs to these algorithms. To fill this gap, we develop a fast simulation-based methodology to determine the stochastic capacity of a region of airspace using integrated weather-traffic models. The developed methodology consists of combining ensemble weather forecast information with an air traffic control algorithm to generate capacity maps over time. We demonstrate the overall methodology through a novel conflict resolution procedure and a simple weather scenario generation tool, and also discuss the potential use of ensemble weather forecasts. An operational study based on comparisons of the generated capacity distributions with observed impacts of weather events on air traffic is also presented.
Prime Ministers and political narratives for policy change: towards a heuristic
Authors: Grube Dennis
Published: October 2012

Political narratives play a central role in modern governance. They explain a government’s driving principles, and underpin their ability to implement policy change. Rhetoric is the tool that Prime Ministers use to articulate and frame political narratives to support their policy prescriptions. This article examines four case studies of how Prime Ministers in Westminster systems have used political rhetoric to create narratives capable of making a persuasive case for policy change. Common themes are explored to provide the basis for a heuristic that encapsulates contemporary prime ministerial practice in articulating political narratives for policy change.
Policy learning? Crisis, evidence and reinvention in the making of public policy
Authors: Hulme Rob , Hulme Moira
Published: October 2012

This article considers the role of evidence and prospects for collective deliberation in shaping policy and practice in straitened times. It draws on critical policy sociology to enhance existing perspectives on policy transfer. The article explores how ‘new professionalism’ in the public services intersects with the ‘new localism’ and current realities of public policy management. In recognising the limitations of ‘presentism’ in policy analysis, attention is afforded to the recuperation and selective reinvention of policy discourses deployed in previous systemic crises. In contrast to rational linear models of problem solving, alternative recursive deliberative approaches are suggested.
Use of sulfur fragments for the synthesis of nitrogen heterocycles
Authors: Padwa Albert
Published: October 2012

This contribution contains a representative sampling from the Padwa laboratory of the conjugate addition of oximes with 2,3-bis(phenylsulfonyl)-1,3-butadiene followed by a subsequent dipolar cycloaddition cascade to produce a variety of alkaloids. The resulting cycloadducts are cleaved reductively to provide azapolycyclic scaffolds with strategically placed functionality for further manipulation of the target compounds.
El nacimiento de un nuevo poder social
Authors: Fernández-Savater Amador
Published: October 2012

La cultura consensual (o "Cultura de la Transición"), que ha gobernado sin réplica en España durante los años ochenta y noventa, es un sistema de información centralizado y unidireccional, en el que los expertos y los intelectuales mediáticos tienen el monopolio de la palabra, las audiencias están sometidas y existen temas intocables. Pero desde el "No a la guerra" en 2003 hasta el 15-M en 2011, movimientos sociales de nuevo tipo erosionan su legitimidad y subvierten su reparto de lo posible y lo imposible, lo visible y lo invisible, el sentido y el ruido, lo real y lo irreal. La crisis de la representación atraviesa hoy todos los órdenes: cultural, político, mediático, intelectual, educativo, etc. Por todos lados surgen nuevos "colectivos de enunciación": voces inesperadas. Y "enunciados imposibles": miradas imprevistas y subversivas sobre el mundo. Son voces "fuera de lugar", que rebosan por fuera de los límites de las instituciones tradicionales (partido, media , sindicato, museo, universidad) y democratizan la producción de sentido. El 15-M ha hecho definitivamente visible para todo el mundo esta crisis, esta apertura y este nuevo poder social.
La imaginación sostenible: culturas y crisis económica en la España actual
Authors: Moreno-Caballud Luis
Published: October 2012

Estudiar el contexto cultural de la actual crisis económica en España permite comprender las formas de vida que la propiciaron y también las que ahora intentan sobrevivir a ella. Frente al modelo del beneficio individual como fin último de la existencia que potenció la burbuja económica, se han desarrollado redes de colaboración y apoyo mutuo que han producido un rico sustrato cultural, favorecido por la expansión del acceso ciudadano a las nuevas tecnologías. En él germinan multitud de proyectos que entienden la cultura como un "procomún", es decir, como un bien compartido por quienes sostienen y disfrutan esos proyectos en cada caso (bibliotecas digitales, colectivos musicales, cooperativas de producción cultural, proyectos transmedia o redes de investigación colaborativa). Estas culturas procomunes generan una "imaginación sostenible", en tanto que apuestan por la reproducción de la vida en común frente a la burbuja individualista y productivista.
Las vidas subprime : la circulación de historias de vida como tecnología de imaginación política en la crisis española (2007-2012)
Authors: Méndez Germán Labrador
Published: October 2012

Este trabajo analiza la circulación de historias de vida en la España de hoy como un género capaz de expresar vidas precarias , entendidas como aquellas que internalizan de modo particular las condiciones históricas y materiales específicas de la temporalidad de crisis o temporalidad de excepción que se abre en el país a partir de 2008. Se argumenta que tal circulación opera como una respuesta a esa misma crisis, en tanto que crisis política y en tanto que crisis de representación, contemplando los efectos que el 15-M, como movimiento social y como mundo discursivo, desarrolla. Esas historias de vida, en su modo de informar y conformar una experiencia de dicha temporalidad, cristalizan en formalizaciones narrativas y ofrecen un género de microrrelato que llamaremos historia de vida subprime. Su intensa circulación en múltiples canales informativos y medios de comunicación y los efectos que alcanzan sobre la producción de actualidad afectan las imágenes colectivas de la vida social contemporánea en la España actual, planteando una redescripción del ámbito de las experiencias políticas y una importante pregunta por las expectativas sociales que definen la cultura española hegemónica.
The Potentiality of the Commons: A Materialist Critique of Cognitive Capitalism from the Cyberbracer@s to the Ley Sinde
Authors: Martín-Cabrera Luis
Published: October 2012

This essay is a critique of immaterial and affective labor, cognitive capitalism and other terms that have been theorized by post-autonomous thinkers such as Antonio Negri, Michael Hardt, Maurizzio Lazzarato, and others. According to these thinkers, under the new wave of financial capitalism, labor has become immaterial and capitalism has become more dependent on cognitive processes in order to enclose external labor and material and symbolic commons. In order to test the validity of these ideas, this essay analyzes the science fiction film Sleep Dealer (2008) by Alex Rivera and the debates triggered by the passing of the so-called Ley Sinde in Spain. The analysis of these seemingly disparate critical terrains reveals a more nuanced picture, one that points to the interdependence of material and immaterial labor, and the need of a less abstract and more intersectional theorization of the commons.
Formas de resistencia en el documental español contemporáneo: en busca de los gestos radicales perdidos
Authors: Benavente Fran
Published: October 2012

1979 es un año decisivo en el ocaso de los gestos comunales de resistencia reactualizados tras las revueltas del 68. El neoliberalismo se abre paso como pensamiento único, aplastando los restos de las utopías sociales. El cineasta español Joaquín Jordá documenta con precisión ese proceso en lo que concierne a España en su filme Numax presenta . . . (1979), una pregnante reflexión sobre el final del cine militante que se ofrece como materialización sangrante de las promesas traicionadas de la Transición española. En 2011 reaparecen gestos de revuelta que reactivan la memoria de algunas prácticas del 68. En este contexto histórico, el presente artículo pretende explorar formas documentales herederas de las de Jordá, que articulan el fantasma de la política para encontrar nuevas estrategias de resistencia ante el discurso totalizador, y determinar de qué modo esa práctica productiva entra en sintonía con los movimientos de los "indignados".
Destello paciente de un escape: notas para una literatura española contemporánea que se fuga
Authors: Fernández Eva
Published: October 2012

¿Desde dónde escribir cuando nuestro mundo está herido y nuestra literatura enferma? Es la pregunta que se plantea una narradora que valora que la reciente narrativa española diagnostica pero no sana. La realidad se había vuelto una con el capitalismo, dijeron, y las siguientes verdades para refundar ya no existen. La narradora se pregunta si a lo mejor no se trata de tener la verdad, sino de serlo. Este artículo explora lo otro que no existe: la verdad, sea esta derrotada, estéloca o a la fuga. La narradora presupone que la literatura tiene la capacidad precisa de imaginar un horizonte que nos posibilite. Para lograrlo, el desafío, que no sabemos imposible , se dirimirá en el terreno de lo material, en las formas de vida y de producir arte corriendo la línea del mar, dado que las múltiples declinaciones del capital parecieron conquistar nuestro horizonte entero.
Virgil Starkwell en la Puerta del Sol: públicos en revuelta, políticas hacia el ser por venir
Authors: Lara Ángel Luis
Published: October 2012

El 15 de mayo de 2011 miles de personas acamparon en el kilómetro cero de España para construir una ciudad dentro de la ciudad. Pronto la energía se propagó por todo el país y las otras ciudades comenzaron a surgir por toda la geografía. Amén de constituir uno de los acontecimientos más relevantes en la historia reciente de España, el 15-M funciona como analizador tanto de la emergencia multitudinaria de nuevas formas de subjetivación y de práctica política, como de la profunda crisis por la que atraviesan en nuestros días las pautas tradicionales de la representación política y de la democracia. El 15-M puede ser analizado tal vez como la primera gran revuelta de los públicos: el viaje multitudinario de los públicos desde su calidad de sujetos del enunciado hacia su condición de sujetos de la enunciación.
Aristotle on Natural Character and Its Implications for Moral Development
Authors: Leunissen Mariska
Published: October 2012

This paper analyzes two components of Aristotle’s physiological discussion of natural character in the biological works: its close causal connection to a living being’s material nature and its changeability due to external environmental factors. As I shall argue, both components are important for our understanding of Aristotle’s views about the moral development of human beings in his ethical treatises. Starting with Aristotle’s ethnographical passage in the Politics ( Pol VII 7, 1327b18–38), according to which differences among the natural character traits of the various nations of human beings—and hence of the ease with which lawgivers can lead them to virtue—are related to the different climates in which they live, this paper fleshes out some of Aristotle’s most prominent views about natural character and its implications for who can and who cannot become virtuous and happy.
Animals, Animal Parts, and Hylomorphism: John Duns Scotus’s Pluralism about Substantial Form
Authors: Ward Thomas M.
Published: October 2012

This paper presents an original interpretation of John Duns Scotus’s theory of hylomorphism. I argue that Scotus thinks, contrary to Aristotle and Thomas Aquinas, that at least some of the extended parts of a substance—paradigmatically the organs of an animal—are themselves substances. Moreover, Scotus thinks that the form of corporeity is nothing more than the substantial forms of these organic parts. I offer an account of how Scotus thinks that the various extended parts of an animal are substantially unified. First, a plurality of substances can become parts of a complex substance if they are essentially ordered to one another in the order of final causality. Second, a plurality of substances do become parts of a complex substance if they are together informed by a soul. The paper closes with some reflections on some of the ramifications of the substancehood of organic parts on the function of soul.
Eve’s Perfection: Spinoza on Sexual (In)Equality
Authors: Sharp Hasana
Published: October 2012

This paper outlines Spinoza’s two diametrically opposed views on the question of sexual equality. In the Political Treatise, he contends that women are naturally inferior to men, and that they are unable to practice virtue. Yet, he presents an antithetical portrait of Eve in his retelling of the Fall in the Ethics. There, Eve’s nature accords perfectly with Adam’s, and their relationship might have promoted virtue in each of them. Attention to Spinoza’s version of the Fall reveals the profound importance of the human bond for the enjoyment of freedom, and the possibility that women are not categorically excluded from Spinoza’s vision of virtue.
Intelligibility and Subjectivity in Peirce: A Reading of His “New List of Categories”
Authors: Gartenberg Zachary Micah
Published: October 2012

It is widely agreed that in his 1867 paper, “On a New List of Categories,” C.S. Peirce performs a transcendental deduction of the categories à la Kant. I argue that he does not. The problem of establishing the veridicality of the categories, the precise aim of Kant’s transcendental deduction, is absent from Peirce’s argument, which in addition does not ground intelligibility in the constitutive acts of a subjective consciousness. The “New List” re-envisions a traditional notion of “representation”—denoting a putative relation between a subjective thought-entity and an objective subject matter—to comprehend instead any system of relations . For Peirce, intelligibility is founded on such systems of relations.
Inventing Intermediates: Mathematical Discourse and Its Objects in Republic VII
Authors: Franklin Lee
Published: October 2012

Plato is commonly taken to be committed to the existence of intermediates , ideal mathematical particulars distinct from Forms. But the main argument by which he is thought to arrive at this commitment makes a problematic assumption about mathematical discourse. By examining the role of mathematics in the philosopher’s education of Republic Bk. VII, I show that Plato does not accept this assumption, and therefore does not endorse the argument for intermediates attributed to him. I then offer a new account on which Plato regards the objects of mathematics as theoretical fictions , objects invented by mathematicians to further their theoretical aims.
European Disintegration?: The Sources of Extremism
Authors: Espada João Carlos
Published: October 2012

Abstract:
The EU is experiencing a somewhat paradoxical phenomenon. On the one hand, it has been a tremendously successful club, promoting democracy and open societies within its borders and in its neighborhoods. On the other hand, the language of national rivalry and of class struggle is re-entering public discourse, especially within the eurozone. The way to solve the paradox is to democratize, or trivialize, the issue of the euro. This means that the euro ought to have a clear exit clause. This, in its turn, means that European democratic elites should learn from their counterparts in the English-speaking democracies—where democracy is a way of life and not a means to achieving a particular purpose. European democrats should me more open to losing an argument about specific purposes, including the euro in its present format, if they really want to strengthen democracy in Europe.
The Opening in Burma: The Need for a Political Pact
Authors: Diamond Larry
Published: October 2012

Abstract:
Burma today is in the midst of what will likely be a drawn-out game of political transition. It is going from a highly authoritarian military regime to something else. It is by no means clear that this will be a transition to democracy—or that the long-ruling military intends genuine democracy to be the destination. If the 2015 elections are to produce a viable democracy rather than a repeat of the 1990 calamity or a deeply resented and unstable semiauthoritarian regime, Burma has a lot of political work to do in the next two years. The good news is that national elections are still three years away. The worrisome news is that the hardest political work of the transition—the negotiation of political pacts—has not yet begun.
Resilient Royals: How Arab Monarchies Hang On
Authors: Yom Sean L. , Gause F. Gregory
Published: October 2012

No monarchy fell to revolution in the Arab Spring. What accounts for this monarchical exceptionalism? Analysts have argued that royal autocracies are inherently more resilient than authoritarian republics due to their cultural foundations and institutional structure. By contrast, this paper leverages comparative analysis to offer a different explanation emphasizing deliberate regime strategies made in circumstances of geographic fortuity. The mobilization of cross-cutting coalitions, hydrocarbon wealth, and foreign patronage account for the resilience of monarchical dictatorships in the Middle East. Without these factors, kingships are just as vulnerable to overthrow as any other autocracy—something that history indicates, given the long list of deposed monarchies in the region over the past half-century.
European Disintegration?: A Fraying Union
Authors: Krastev Ivan
Published: October 2012

Abstract:
Once we acknowledge that disintegration of the EU is a “thinkable” option, it becomes important to grasp what “the collapse of the Union” would mean. How can the “disintegration” of the Union be defined or conceptualized? Would the departure of just one country from the eurozone or from the EU itself amount to “disintegration”? Contrary to the expectations of some democratic theorists, the EU will not collapse because of the “democratic deficit” of European institutions. Nor will it be saved by the democratic mobilization of civil society. Paradoxically, it is widespread disillusionment with democracy—the shared belief that national governments are powerless in the face of global markets—that may be the best hope for reconciling the growing tension between the goal of further European integration and the goal of deepening democracy in Europe.
Politics in Crisis?
Authors: Hassner Pierre
Published: October 2012

Politics is dying, politics is dead! This funeral oration is delivered time and again, but what is it that is being mourned? The classless society and the withering away of the state predicted by Marx? The advent of Nietzsche’s “last man,” of a world resembling a herd with no shepherd, where everyone finds it too burdensome to rule or to obey, or to enter into conflict with others? Or is it the arrival, denounced by Hannah Arendt, of a society in which action defined by politics (that is, by public dialogue and by war) has been displaced by production, and then by consumption—in other words, by a purely biological life in which politics is revived only fleetingly in the rare revolutionary moments when citizens meet and talk?