Entry in the ADHD drugs market: Welfare impact of generics and me-toos

Recent decades have seen a growth in treatments for attention deficit hyperactivity disorder (ADHD) including many branded and generic drugs. In the early 2000's, new drug entry dramatically altered market shares. We estimate a demand system for ADHD drugs and assess the welfare impact of new drugs. We find that entry induced large welfare gains by reducing prices of substitute drugs, and by providing alternative delivery mechanisms for existing molecules. Our results suggest that the success of follow-on patented drugs may come from unanticipated innovations like delivery mechanisms, a factor ignored by proposals to retard new follow-on drug approvals

MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments

MAP2 and tau exhibit microtubule-stabilizing activities that are implicated in the development and maintenance of neuronal axons and dendrites. The proteins share a homologous COOH-terminal domain, composed of three or four microtubule binding repeats separated by inter-repeats (IRs). To investigate how MAP2 and tau stabilize microtubules, we calculated 3D maps of microtubules fully decorated with MAP2c or tau using cryo-EM and helical image analysis. Comparing these maps with an undecorated microtubule map revealed additional densities along protofilament ridges on the microtubule exterior, indicating that MAP2c and tau form an ordered structure when they bind microtubules. Localization of undecagold attached to the second IR of MAP2c showed that IRs also lie along the ridges, not between protofilaments. The densities attributable to the microtubule-associated proteins lie in close proximity to helices 11 and 12 and the COOH terminus of tubulin. Our data further suggest that the evolutionarily maintained differences observed in the repeat domain may be important for the specific targeting of different repeats to either α or β tubulin. These results provide strong evidence suggesting that MAP2c and tau stabilize microtubules by binding along individual protofilaments, possibly by bridging the tubulin interfaces

A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes.

International audienceReactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of the β-dicarbonyl compounds with their enol forms, a 1,3-dipolar cycloaddition of the enol forms with the aryl azides (high activation energy), and a dehydration process (lower activation energy). The effect of non-conventional activation methods on the degradation of 1,2,3-triazolines was next studied experimentally. Finally, some of the 1,2,3-triazoles such synthesized were evaluated for their bactericidal and cytotoxic activities

Forgetting feelings: Opposite biases in reports of the intensity of past emotion and mood.

Memory for feelings is subject to fading and bias over time. In 2 studies, the authors examined whether the magnitude and direction of bias depend on the type of feeling being recalled: emotion or mood. A few days after the U.S. Presidential elections in 2008 and 2012, participants reported how they felt about the election outcome (emotion) and how they felt in general (mood). A month after the elections, participants recalled their feelings. The intensity of past emotion was recalled more accurately than the intensity of past mood. Participants underestimated the intensity of emotion but overestimated the intensity of mood. Participants' appraisals of the importance of the election, which diminished over time, contributed to underestimating the intensity of emotion. In contrast, participants' strong emotional response to the election contributed to overestimating the intensity of mood. These opposing biases have important implications for decision making and clinical assessment

Disease-related factors affecting timely lymphoma diagnosis : a qualitative study exploring patient experiences

Background Expediting cancer diagnosis is widely perceived as one way to improve patient outcomes. Evidence indicates that lymphoma diagnosis is often delayed, yet understanding of issues influencing this is incomplete. Aim To explore patients' and their relatives' perceptions of disease-related factors affecting time to diagnosis of Hodgkin and non-Hodgkin lymphoma. Design and setting Qualitative UK study involving patients with indolent and aggressive lymphomas, and their relatives, from an established population-based cohort in the north of England. Method Semi-structured interviews with 35 patients and 15 of their relatives. Interviews were audiorecorded and transcribed, and qualitative descriptive analysis was undertaken. Results Participant accounts suggest that certain features of lymphoma can impact on patients' and healthcare providers' (HCPs) responses to disease onset. Three characteristics stand out: disease occurrence (rare), manifestation (varied), and investigative options (often inconclusive). Interviewees described how they, and some HCPs, lacked familiarity with lymphoma, seldom considering it a likely explanation for their symptoms. Symptoms reported were highly variable, frequently non-specific, and often initially thought to be associated with various benign, self-limiting causes. Blood tests and other investigations, while frequently able to detect abnormalities, did not reliably indicate malignancy. Interviewees reported the potential for improvements among HCPs in information gathering, communication of uncertainty, and re-presentation advice for non-resolving/ progressive health changes. Conclusion This study demonstrates the complex characteristics of lymphoma, perceived by patients as prolonging time to diagnosis, often despite significant effort by themselves, their relatives, and HCPs to expedite this process. The findings also illustrate why simple solutions to delayed diagnosis of lymphoma are lacking