Honeycutt Liu (turkeywood8)

Food and Drug Administration (FDA) rules restrict pharmaceutical manufacturers from promoting drugs for non-FDA-approved (off-label) indications. When manufacturers violate this rule, it has in many cases led to unsafe prescribing. However, in 2012, a federal circuit court ruled in United States v. Caronia that truthful off-label promotion was protected under the First Amendment, threatening government enforcement in this area. The authors extracted cases from the WestLawNext database that mentioned Caronia from 2012 to 2019. They collected information about plaintiff, procedural history, product and manufacturer involved, and case outcome. Cases were categorized as either "follows," "does not follow," or "distinguishes" from Caronia. The authors qualitatively reviewed the full text of each case to verify whether Caronia was given substantive discussion for perceptions of off-label promotion, application of commercial speech rights, and how courts interpreted Caronia. Among 42 cases in the study cohort, 22 (52%) followed Caronia's core holding that truthful, non-misleading off-label promotion was not actionable under FDA rules. By contrast, 20 cases (48%) treated Caronia negatively, either declining to follow (9 cases) or distinguishing it (11 cases). Enforcement of restrictions on off-label marketing became more challenging after Caronia. This gives manufacturers greater flexibility to promote drugs for unapproved uses despite the substantial public health risks. Enforcement of restrictions on off-label marketing became more challenging after Caronia. This gives manufacturers greater flexibility to promote drugs for unapproved uses despite the substantial public health risks. Many recent advancements in single molecule localisation microscopy exploit the stochastic photo-switching of fluorophores to reveal complex cellular structures beyond the classical diffraction limit. However, this same stochasticity makes counting the number of molecules to high precision extremely challenging, preventing key insight into the cellular structures and processes under observation. Modelling the photo-switching behaviour of a fluorophore as an unobserved continuous time Markov process transitioning between a single fluorescent and multiple dark states, and fully mitigating for missed blinks and false positives, we present a method for computing the exact probability distribution for the number of observed localisations from a single photo-switching fluorophore. This is then extended to provide the probability distribution for the number of localisations in a dSTORM experiment involving an arbitrary number of molecules. We demonstrate that when training data is available to estimate photoswitching rates, the unknown number of molecules can be accurately recovered from the posterior mode of the number of molecules given the number of localisations. Finally, we demonstrate the method on experimental data by quantifying the number of adapter protein Linker for Activation of T cells (LAT) on the cell surface of the T cell immunological synapse. Software available at https//github.com/lp1611/mol_count_dstorm. Supplementary data are available at Bioinformatics online. Supplementary data are available at Bioinformatics online. This article explains the policy process that occasioned the development of comprehensive tobacco control policies in Mauritius from 1980 to 2019. It does so by drawing theoretical insights from John Kingdon's streams framework, historical institutionalism, and ideational perspectives to explicate how tobacco control rose to the status of government policy agenda. The main sources of data are government documents, media reports, archival studies, grey literature, and published books and articles. Linsitinib These sources were supplemented by key informant interviews with government officials, civil society groups, and