BEYOND THE INERTIA OF AFFLUENCE

O aquecimento global engendra perigos sem precedentes para a humanidade e é um produto de atividades humanas: a produção e o consumo de combustíveis fósseis, acompanhados de níveis cada vez maiores de gases de efeito estufa na atmosfera. Algumas das consequências previstas do aquecimento já se fazem presentes; efeitos ainda mais catastróficos serão experimentados no futuro. Dois processos comportamentais operam para manter o uso de combustíveis fósseis: 1) Estudos sobre descontos do atraso das consequências sugerem que resultados de valor relativamente menor que estão disponíveis agora (e.g., dirigir carros pessoais) são provavelmente preferidos frente ao valor de um planeta sustentável para toda a humanidade, a ser atingido em um futuro indefinido e 2) atividades atuais que envolvem o uso de combustíveis fósseis são, provavelmente, muito persistentes devido à longa e rica história de reforçamento para indivíduos (e.g., conforto e conveniência) e para a indústria de combustíveis fósseis como um todo (e.g., empregos e lucros). Uma maneira de confrontar essa persistência é taxar as emissões de gases de efeito estufa, o que pode transferir os incentivos atuais da energia baseada em combustíveis fósseis para as energias renováveis, mesmo que o abrandamento final das mudanças climáticas seja remoto. As contingências de taxação do carbono são semelhantes às empregadas para tratar o comportamento problema; descreve-se um exemplo bem-sucedido desta abordagem.Palavras-chave: aquecimento global, consumo de combustível fóssil, taxação do carbono, desvalorização pelo atraso, momento do comportamento. Global warming poses unprecedented dangers to humankind, and it is a product of human activities: Production and consumption of fossil fuels, accompanied by steadily increasing levels of greenhouse gasses in the atmosphere.  Some of the predicted consequences of warming are already upon us; yet more catastrophic effects will be experienced in the future.  Two behavioral processes operate to maintain fossil fuel use: 1) Delay discounting studies suggest that relatively lesser-valued outcomes (e.g., driving private cars) that are available now are likely to be preferred to the value of a sustainable planet for all humankind, to be achieved in the indefinite future; and 2) ongoing fossil-fueled activities are likely to be highly persistent because of the long and rich history of reinforcement for individuals (e.g., comfort and convenience) and for the fossil-fuel industry as a whole (e.g., jobs and profits). One way to counter that persistence is to tax greenhouse gas emissions, which can shift current incentives away from fossil-fuel based energy toward renewables, even though the ultimate slowing of climate change may be remote.  Carbon-tax contingencies are similar to those employed to treat problem behavior; a successful example of this approach is described.Key words:  Global warming, fossil fuel consumption, carbon tax, delay discounting, behavioral momentu

Behavioral Momentum Theory: Equations and Applications

Behavioral momentum theory provides a quantitative account of how reinforcers experienced within a discriminative stimulus context govern the persistence of behavior that occurs in that context. The theory suggests that all reinforcers obtained in the presence of a discriminative stimulus increase resistance to change, regardless of whether those reinforcers are contingent on the target behavior, are noncontingent, or are even contingent on an alternative behavior. In this paper, we describe the equations that constitute the theory and address their application to issues of particular importance in applied settings. The theory provides a framework within which to consider the effects of interventions such as extinction, noncontingent reinforcement, differential reinforcement of alternative behavior, and other phenomena (e.g., resurgence). Finally, the theory predicts some counterintuitive and potentially counterproductive effects of alternative reinforcement, and can serve as an integrative guide for intervention when its terms are identified with the relevant conditions of applied settings

Delayed Matching to Sample: Reinforcement has Opposite Effects on Resistance to Change in Two Related Procedures

The effects of reinforcement on delayed matching to sample (DMTS) have been studied in two within-subjects procedures. In one, reinforcer magnitudes or probabilities vary from trial to trial and are signaled within trials (designated signaled DMTS trials). In the other, reinforcer probabilities are consistent for a series of trials produced by responding on variable-interval (VI) schedules within multiple-schedule components (designated multiple VI DMTS). In both procedures, forgetting functions in rich trials or components are higher than and roughly parallel to those in lean trials or components. However, during disruption, accuracy has been found to decrease more in rich than in lean signaled DMTS trials and, conversely, to decrease more in lean than in rich multiple VI DMTS components. In the present study, we compared these procedures in two groups of pigeons. In baseline, forgetting functions in rich trials or components were higher than and roughly parallel to those in lean trials or components, and were similar between the procedures. During disruption by prefeeding or extinction, accuracy decreased more in rich signaled DMTS trials, whereas accuracy decreased more in lean multiple VI DMTS components. These results replicate earlier studies and are predicted by a model of DMTS from Nevin, Davison, Odum, and Shahan (2007)

The Momentum of Human Behavior in a Natural Setting

Adults with mental retardation in a group home received popcorn or coffee reinforcers for sorting plastic dinnerware. In Part 1 of the experiment, reinforcers were dispensed according to a variable-interval 60-s schedule for sorting dinnerware of one color and according to a variable-interval 240-s schedule for sorting dinnerware of a different color in successive components of a multiple schedule. Sorting rates were similar in baseline, but when a video program was shown concurrently, sorting of dinnerware was more resistant to distraction when correlated with a higher rate of reinforcement. In Part 2 of the experiment, popcorn or coffee reinforcers were contingent upon sorting both colors of dinnerware according to variable-interval 60-s schedules, but additional reinforcers were given independently of sorting according to a variable-time 30-s schedule during one dinnerware-color component. Baseline sorting rate was lower but resistance to distraction by the video program was greater in the component with additional variable-time reinforcers. These results demonstrate that resistance to distraction depends on the rate of reinforcers obtained in the presence of component stimuli but is independent of baseline response rates and response-reinforcer contingencies. Moreover, these results are similar to those obtained in laboratory studies with pigeons, demonstrating that the determination of resistance to change by stimulus-reinforcer relations is not confined to controlled laboratory settings or unique to the pigeon

Astrometry with the Keck-Interferometer: the ASTRA project and its science

The sensitivity and astrometry upgrade ASTRA of the Keck Interferometer is introduced. After a brief overview of the underlying interferometric principles, the technology and concepts of the upgrade are presented. The interferometric dual-field technology of ASTRA will provide the KI with the means to observe two objects simultaneously, and measure the distance between them with a precision eventually better than 100 uas. This astrometric functionality of ASTRA will add a unique observing tool to fields of astrophysical research as diverse as exo-planetary kinematics, binary astrometry, and the investigation of stars accelerated by the massive black hole in the center of the Milky Way as discussed in this contribution.Comment: 22 pages, 10 figures (low resolution), contribution to the summerschool "Astrometry and Imaging with the Very Large Telescope Interferometer", 2 - 13 June, 2008, Keszthely, Hungary, corrected authorlis

Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group

IntroductionMalignant pleural mesothelioma (MPM) is an aggressive malignancy that most often presents at an advanced, incurable stage. After the failure of standard first-line cisplatin/antifolate chemotherapy, there is no accepted treatment. The vascular endothelial growth factor pathway may be a relevant therapeutic target in MPM.MethodsThis open-labeled phase II trial evaluated single-agent sunitinib, an inhibitor of multiple receptor tyrosine kinases including the vascular endothelial growth factor receptors, given at 50 mg daily orally for 4 weeks followed by a 2-week rest, in patients with advanced MPM. Two cohorts were studied: cohort 1, in which patients had previously received cisplatin-based chemotherapy, and cohort 2, consisting of previously untreated patients. A two-stage design was used for both cohorts; the primary outcome was objective response rate as determined by the RECIST criteria modified for MPM. Secondary outcomes included rates and duration of disease control, progression-free survival and overall survival, and safety and tolerability.ResultsA total of 35 eligible patients were enrolled (17 to cohort 1 and 18 to cohort 2). Neither cohort met the criteria for continuing to the second stage of accrual; only one objective response, confirmed by independent review, was observed in a previously untreated patient. Median progression-free and overall survivals were 2.8 and 8.3 months in cohort 1, and 2.7 and 6.7 months in cohort 2, respectively. Observed toxicity was within that expected for sunitinib.ConclusionsSunitinib, similar to other angiogenesis inhibitors, has limited activity in MPM. Future trials of angiogenesis inhibitors given as single agents in unselected patients with MPM are not warranted

Longitudinal metabolite changes in progressive multiple sclerosis:A study of 3 potential neuroprotective treatments

Background: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. Study-type: Longitudinal. Population: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. Field strength/sequence: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. Assessment: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. Statistical tests: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. Results: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. Data conclusion: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. Level of evidence: 1 TECHNICAL EFFICACY: Stage 4

Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments

BACKGROUND: 1 H-magnetic resonance spectroscopy (1 H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS). PURPOSE: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by 1 H-MRS and their association with clinical disability in SPMS. STUDY-TYPE: Longitudinal. POPULATION: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%]. FIELD STRENGTH/SEQUENCE: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1. ASSESSMENT: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks. STATISTICAL TESTS: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant. RESULTS: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks. DATA CONCLUSION: 1 H-MRS demonstrated altered membrane turnover over 96-weeks in the placebo group. It also distinguished changes in neuro-metabolites related to gliosis and glutaminergic transmission, due to fluoxetine and riluzole, respectively. Data show tNAA is a potential marker for upper limb function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4

Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Gefitinib, a small molecule tyrosine kinase inhibitor of the Epidermal Growth Factor Receptor (<it>EGFR</it>), has shown limited efficacy in the treatment of lung cancer. Recognized clinical predictors of response to this drug, specifically female, non-smoker, Asian descent, and adenocarcinoma, together suggest a genetic basis for drug response. Recent studies have addressed the relationship between response and either sequence mutations or increased copy number of specific receptor tyrosine kinases. We set out to examine the relationship between response and the molecular status of two such kinases, <it>EGFR </it>and <it>HER2</it>, in 39 patients treated with gefitinib at the BC Cancer Agency.</p> <p>Methods</p> <p>Archival patient material was reviewed by a pathologist and malignant cells were selectively isolated by laser microdissection or manual recovery of cells from microscope slides. Genomic DNA was extracted from 37 such patient samples and exons 18–24, coding for the tyrosine kinase domain of <it>EGFR</it>, were amplified by PCR and sequenced. <it>EGFR </it>and <it>HER2 </it>copy number status were also assessed using FISH in 26 samples. Correlations between molecular features and drug response were assessed using the two-sided Fisher's exact test.</p> <p>Results</p> <p>Mutations previously correlated with response were detected in five tumours, four with exon 19 deletions and one with an exon 21 missense L858R point mutation. Increased gene copy number was observed in thirteen tumours, seven with <it>EGFR </it>amplification, three with <it>HER2 </it>amplification, and three with amplification of both genes. In our study cohort, a correlation was not observed between response and <it>EGFR </it>mutations (exon 19 deletion p = 0.0889, we observed a single exon 21 mutation in a non-responder) or increases in <it>EGFR </it>or <it>HER2 </it>copy number (p = 0.552 and 0.437, respectively).</p> <p>Conclusion</p> <p>Neither mutation of <it>EGFR </it>nor increased copy number of <it>EGFR </it>or <it>HER2 </it>was diagnostic of response to gefitinib in this cohort. However, validation of these features in a larger sample set is appropriate. Identification of additional predictive biomarkers beyond <it>EGFR </it>status may be necessary to accurately predict treatment outcome.</p