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In their efforts to affect regulations, firms have developed specific strategies to exploit scientific uncertainty. They have manufactured doubt by hiring and funding dissenting scientists, by producing and publicizing favorable scientific findings and by generally concealing their involvement in biased research. We propose a new model to study the interplay between scientific uncertainty, firms' miscommunication and public policies. The government is benevolent but populist, and maximizes social welfare as perceived by citizens. The industry can produce costly reports showing that its activity is not harmful. Citizens are unaware of the industry's miscommunication. We first characterize the industry's optimal miscommunication policy. The industry notably ceases miscommunicating abruptly when scientists' belief reaches a critical threshold. We identify a natural condition under which miscommunication is stronger under a tax on emissions than under command and control. We then analyze research funding. A populist government may support research to enable firms to falsely reassure citizens. Establishing an independent research agency helps limit the welfare losses induced by populist policies. [ABSTRACT FROM AUTHOR]

We document strong and robust negative correlations between the length of the title of an economics article and different measures of scientific quality. Analyzing all articles published between 1970 and 2011 and referenced in EconLit , we find that articles with shorter titles tend to be published in better journals, to be more cited and to be more innovative. These correlations hold controlling for unobserved time-invariant and observed time-varying characteristics of teams of authors. [ABSTRACT FROM AUTHOR]

We study network games under strategic complementarities. Agents are embedded in a fixed network. They choose a positive, continuous action and interact with their network neighbors. Interactions are positive and actions are bounded from above. We first derive new sufficient conditions for uniqueness, covering all concave as well as some non-concave best responses. We then study the relationship between position and action and identify situations where a more central agent always plays a higher action in equilibrium. We finally analyze comparative statics. We show that a shock may not propagate throughout the entire network and uncover a general pattern of decreasing interdependence. [ABSTRACT FROM AUTHOR]

Abstract: A new flow-through system for the production of [11C]phosgene, a versatile labelling agent in radiochemistry for PET, is described. Cyclotron-produced [11C]CH4 is mixed with Cl2 and converted into [11C]CCl4 by passing the mixture through an empty quartz tube at 510°C. The outflow is directed through a Sb-filled guard that takes out Cl2 and then, without intentional O2 addition, through a second empty quartz tube at 750°C, giving rise to [11C]phosgene in 30–35% radiochemical yield. [Copyright &y& Elsevier]

Abstract: This paper considers the formation of risk-sharing networks. Following empirical findings, we build a model where pairs form links, but a population cannot coordinate links. As a benchmark, individuals commit to share monetary holdings equally with linked partners. We find efficient networks can (indirectly) connect all individuals and involve full insurance. But equilibrium networks connect fewer individuals. When breaking links, individuals do not consider negative externalities on others in the network. Thus identical individuals can end up in different positions in a network and have different outcomes. These results may help to explain empirical findings that risk-sharing is often asymmetric. [Copyright &y& Elsevier]

Abstract: This paper studies the first model of social interactions with anti-coordination. Agents have fixed partners with whom they play a common bilateral game of anti-coordination, like the chicken game. Partnerships are represented as links of a network. The paper asks: How do social interactions interplay with the incentives to anti-coordinate? How does the social network affect individual choices in equilibrium? The analysis shows that network effects are much stronger than when partners play a coordination game. The network notably affects how agents respond when a strategy becomes more advantageous. In the standard benchmark of complete interactions, more agents play the strategy. This result does not generally hold when the network is incomplete. On bipartite networks, agents'' choices are unaffected, while on core-periphery networks, less agents may play the strategy. [Copyright &y& Elsevier]

We study a setting in which individual players choose their partners as well as a mode of behavior in 2×2 anti-coordination games - games where a player’s best response is to choose an action unlike that of her partner. We characterize the equilibrium networks as well as study the effects of network structure on individual behavior. Our analysis shows that both network architecture and induced behavior crucially depend on the value of the cost of forming links. In general, equilibrium configurations are found to be neither unique nor efficient. [ABSTRACT FROM AUTHOR]

Abstract: Recently, a novel series of amidines has been described, exhibiting high NR2B-subtype selective N-methyl-D-aspartate (NMDA) antagonist activity with nanomolar or subnanomolar affinity. Within the styrylamidine subclass, (E)-N-(2-methoxybenzyl)-3-phenyl-acrylamidine (1), displayed the highest affinity (Ki=0.7nM versus [3H]ifenprodil) and was considered an appropriate candidate for isotopic labelling with carbon-11 (T 1/2: 20.38min) at its methoxy group for imaging of NMDA receptors with PET. Derivative 1 has been labelled from the corresponding nor-analogue using [11C]methyl triflate and the following experimental conditions : (1) trapping at −10°C of [11C]methyl triflate in 300μL of acetone containing 0.6–0.8mg of precursor 5 (2.4–3.2μmol) and 5μL of a 3M solution of NaOH in water (about 5eq.); (2) concentration to dryness of the reaction mixture (at 110°C, using a helium stream for 1–2min); (3) taking up the residue with 0.5mL of the HPLC mobile phase and (4) purification using semi-preparative HPLC (SymmetryPrep® C-18, Waters, 300×7.8mm). Typically, starting from a 1.5 Ci (55.5GBq) [11C]CO2 production batch, 120–240m Ci (4.44–8.88GBq) of [11C]-1 (20–40% decay-corrected radiochemical yield, ) was obtained within a total synthesis time of 25–30min. Specific radioactivities ranged from 0.8 to 1.2Ci/μmol (29.6–44.4GBq/μmol) at the end of radiosynthesis. No attempts were made to further optimise these reactions, as sufficient material was obtained to allow for preliminary pharmacological characterisation. [Copyright &y& Elsevier]

Background: Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results: [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions: Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low. [ABSTRACT FROM AUTHOR]

[11C]SL-25.1188 [(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[ d]isoxazol-3-yl]-oxazolidin-2-one], an oxazolidinone derivative, was characterized in baboons as a radioligand for the in vivo visualization of MAO-B using positron emission tomography (PET). After i.v. injection, [11C]SL25.1188 presented a rapid phase of distribution in blood (about 5 min), followed by a T1/2 elimination of 85 ± 14 min. Plasma metabolism analysis showed that [11C]SL25.1188 is stable in vivo at least for 30 min. Brain uptake was rapid with the highest one observed in the striatum and thalamus, and the lowest in the pons. Calculated distribution volumes ( VT) were as follows: striatum = 10.3, thalamus = 10.9, hippocampus = 8.9, temporal cortex = 7.7, occipital cortex = 7.2, parietal cortex = 7.4, frontal cortex = 7.4, white matter = 7.4, and pons = 6.1. Pretreatment with deprenyl (2 mg/kg, i.v.) or lazabemide (0.5 mg/kg, i.v.) reduced VT values in all brain areas up to 50%. In displacement experiments, injection of SL25.1188 or deprenyl (1 and 2 mg/kg, i.v., respectively) strongly reduced the specific uptake of [11C]SL25.1188 in all brain areas (85-100%), while a lesser displacement was observed with lazabemide (0.5 mg/kg, i.v.) (55-70% of specific binding depending on the brain area). Therefore, [11C]SL25.1188 is characterized in vivo by reversible binding, high brain uptake and very slow plasma metabolism, strongly suggesting that this radioligand is a potent tool for the in vivo study of brain MAO-B. Synapse 64:61-69, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this study was to quantify D2 receptors density and affinity in living rats using [11C]raclopride and to validate the multiinjection modelling approach. To this aim, we used an intracerebral β+-sensitive probe as a highly sensitive system to quantify the radioligand activity using a single three-injection experimental paradigm. The study was divided into three main parts: (i) [11C]raclopride catabolism evaluation without and with cimetidine pretreatment (cytochrome P450 inhibitor); (ii) quantification of kinetics parameters in the striatum, enthorinal cortex, and cerebellum of living rats using a three-compartment model with an arterial input function; (iii) correlation study of in vivo and in vitro binding density and affinity values in the same striatal tissues. (i) raclopride catabolism was very reproducible between individuals; cimetidine pre-treatment resulted in a 30% reduction of raclopride metabolites. (ii) D2 striatal B′max and KdVr estimates obtained by compartmental modelling were 19.87±6.45 and 6.2±3.3 nmol/L, respectively. Cerebellum is the best candidate as a reference region with no specific binding detectable in vivo. (iii) When comparing density (Bmax/B′max) and affinity (Kd/KdVr) values in vivo and in vitro for each striatum, a high strict correlation was found (r2=0.90 and 0.72, for density and affinity, respectively). These results validate the multi-injection modelling approach coupled to β-microprobe acquisitions as a mean to provide accurate and separate estimates of dopamine D2-receptor density and affinity, in the living rodent striatum.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1517–1527. doi:10.1038/sj.jcbfm.9600141; published online 25 May 2005 [ABSTRACT FROM AUTHOR]

Recently, a new series of potent and highly subtype-selective 1-(heteroarylalkynyl)-4-benzylpiperidine antagonists of the NMDA receptors has been described by Pfizer Laboratories. In this series, 5-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-one (1) was identified as a selective antagonist for the NR1A/2B subtype, displaying IC50 values for inhibition of the NMDA responses of 5.3 nM for this subtype (compared to NR1A/2A: 35 μM and NR1A/2C>100 μM) and was active in rat at a relatively low dosage (10 mg/kg po). Derivative 1 has been synthesized in four chemical steps in good overall yield and labelled with carbon-11 T1/2: 20.4 min at its benzoimidazolone ring using [11C]phosgene. The pharmacological profile of [11C]-1 was evaluated in vivo in rats with biodistribution studies and brain radioactivity monitored with intracerebral radiosensitive β-microprobes. The brain uptake of [11C]-1 was extremely low (0.07% I.D./mL on average at 30 min) and rather uniform across the different brain structures. This in vivo brain regional distribution of [11C]-1 did not match with autoradiographic or binding data obtained with other NR2B subtype-selective NMDA ligands. Competition studies with ifenprodil (20 mg/kg, ip, 30 min before the radiotracer injection) failed to demonstrate specific binding of the radiotracer in the brain. In view of these results, and especially considering the low brain penetration of the radiotracer, [11C]-1 does not have the required properties for imaging NMDA receptors using positron emission tomography. [Copyright &y& Elsevier]

Considerable efforts have been engaged in the design, synthesis and pharmacological characterization of radioligands for imaging the serotonin transporter, based on its implication in several neuropsychiatric diseases, such as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series, the fluoro derivative has been designed for positron emission tomography (PET). The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference compound have been synthesized. 5-[18F]Fluoro-6-nitroquipazine has been radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life) by nucleophilic aromatic substitution from the corresponding N-Boc protected 5-bromo- and 5-chloro-precursors using K[18F]F-K222 complex in DMSO by conventional heating (145 °C, 2 min) or microwave activation (50 W, 30–45 s), followed by removal of the protective group with TFA. Typically, 15–25 mCi (5.5–9.2 GBq) of 5-[18F]fluoro-6-nitroquipazine (1–2 Ci/μmol or 37–72 GBq/μmol) could be obtained in 70–80 min starting from a 550–650 mCi (20.3–24.0 GBq) aliquot of a cyclotron [18F]F− production batch (2.7–3.8% non decay-corrected yield based on the starting [18F]fluoride). Ex vivo studies (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5-[18F]fluoro-6-nitroquipazine ([18F]-1d) readily crossed the blood brain barrier and accumulated in the regions rich in 5-HT transporter (frontal- and posterial cortex, striata). However, the low accumulation of the tracer in the thalamus (rat and monkey) as well as the comparable displacement of the tracer observed with both citalopram, a -HT re-uptake inhibitor and maprotiline, a norepinephrine re-uptake inhibitor (rat), indicate that 5-[18F]fluoro-6-nitroquipazine ([18F]-1d) does not have the suggested potential for PET imaging of the serotin transporter (SERT). [Copyright &y& Elsevier]