540 research outputs found
Five Principles for Vertical Merger Enforcement Policy
There seems to be consensus that the Department of Justice’s 1984 Vertical Merger Guidelines do not reflect either modern theoretical and empirical economic analysis or current agency enforcement policy. Yet widely divergent views of preferred enforcement policies have been expressed among agency enforcers and commentators. Based on our review of the relevant economic literature and our experience analyzing vertical mergers, we recommend that the enforcement agencies adopt five principles: (i) The agencies should consider and investigate the full range of potential anticompetitive harms when evaluating vertical mergers; (ii) The agencies should decline to presume that vertical mergers benefit competition on balance in the oligopoly markets that typically prompt agency review, nor set a higher evidentiary standard based on such a presumption; (iii) The agencies should evaluate claimed efficiencies resulting from vertical mergers as carefully and critically as they evaluate claimed efficiencies resulting from horizontal mergers, and require the merging parties to show that the efficiencies are verifiable, merger-specific and sufficient to reverse the potential anticompetitive effects; (iv) The agencies should decline to adopt a safe harbor for vertical mergers, even if rebuttable, except perhaps when both firms compete in unconcentrated markets; (v) The agencies should consider adopting rebuttable anticompetitive presumptions that a vertical merger harms competition when certain factual predicates are satisfied. We do not intend these presumptions to describe all the ways by which vertical mergers can harm competition, so the agencies should continue to investigate vertical mergers that raise concerns about input and customer foreclosure, loss of a disruptive or maverick firm, evasion of rate regulation or other threats to competition, even if the specific factual predicates of the presumptions are not satisfied
Methods in literature-based drug discovery
This dissertation work implemented two literature-based methods for predicting new therapeutic uses for drugs, or drug reprofiling (also known as drug repositioning or drug repurposing). Both methods used data stored in ChemoText, a repository of MeSH terms extracted from Medline records and created and designed to support drug discovery algorithms. The first method was an implementation of Swanson's ABC paradigm that used explicit connections between disease, protein, and chemical annotations to find implicit connections between drugs and disease that could be potential new therapeutic drug treatments. The validation approach implemented in the ABC study divided the corpus into two segments based on a year cutoff. The data in the earlier or baseline period was used to create the hypotheses, and the later period data was used to validate the hypotheses. Ranking approaches were used to put the likeliest drug reprofiling candidates near the top of the hypothesis set. The approaches were successful at reproducing Swanson's link between magnesium and migraine and at identifying other significant reprofiled drugs. The second literature-based discovery method used the patterns in side effect annotations to predict drug molecular activity, specifically 5-HT6 binding and dopamine antagonism. Following a study design adopted from QSAR experiments, side effect information for chemicals with known activity was input as binary vectors into classification algorithms. Models were trained on this data to predict the molecular activity. When the best validated models were applied to a large set of chemicals in a virtual screening step, they successfully identified known 5-HT6 binders and dopamine antagonists based solely on side effect profiles. Both studies addressed research areas relevant to current drug discovery, and both studies incorporated rigorous validation steps. For these reasons, the text mining methods presented here, in addition to the ChemoText repository, have the potential to be adopted in the computational drug discovery laboratory and integrated into existing toolsets
Serologic Evidence of H1 Swine Influenza Virus Infection in Swine Farm Residents and Employees
We evaluated seropositivity to swine and human H1 influenza viruses in 74 swine farm owners, employees, their family members, and veterinarians in rural south-central Wisconsin, compared with 114 urban Milwaukee, Wisconsin, residents. The number of swine farm participants with positive serum hemagglutination-inhibition (HI) antibody titers >40 to swine influenza viruses (17/74) was significantly higher (p<0.001) than the number of seropositive urban control samples (1/114). The geometric mean serum HI antibody titers to swine influenza viruses were also significantly higher (p<0.001) among the farm participants. Swine virus seropositivity was significantly (p<0.05) associated with being a farm owner or a farm family member, living on a farm, or entering the swine barn >4 days/week. Because pigs can play a role in generating genetically novel influenza viruses, swine farmers may represent an important sentinel population to evaluate the emergence of new pandemic influenza viruses
Recommendations and Comments on the Draft Vertical Merger Guidelines
These recommendations and comments respond to the request by the Federal Trade Commission and the Department of Justice’s Antitrust Division for public comment on the draft 2020 Vertical Merger Guidelines. We commend the agencies for updating the 1984 non-horizontal merger guidelines by recognizing the substantial advances in economic thinking about vertical mergers in the thirty-five years since those guidelines were issued. Our comments emphasize four issues: (i) the treatment of the elimination of double marginalization (“EDM”), particularly that the draft vertical merger guidelines appear inappropriately to make proof of cognizability part of the agencies burden and that they appear to inappropriately treat the merging firm’s failure to have eliminated double marginalization pre-merger as proof that the merger would lead to EDM and that the post-merger EDM would be merger-specific; (ii) the seemingly arbitrary and inappropriately permissive safe harbor; (iii) the inappropriate (though perhaps unintended) apparent requirement that harms be quantified; and (iv) the inappropriate (though perhaps unintended) apparent requirement that the agencies show that foreclosure would not have been profitable before the merger. We are concerned that these features of the draft Guidelines will lead to under-enforcement and false negatives (including under-deterrence)
Mining connections between chemicals, proteins, and diseases extracted from Medline annotations
The biomedical literature is an important source of information about the biological activity and effects of chemicals. We present an application that extracts terms indicating biological activity of chemicals from Medline records, associates them with chemical name and stores the terms in a repository called ChemoText. We describe the construction of ChemoText and then demonstrate its utility in drug research by employing Swanson’s ABC discovery paradigm. We reproduce Swanson’s discovery of a connection between magnesium and migraine in a novel approach that uses only proteins as the intermediate B terms. We validate our methods by using a cutoff date and evaluate them by calculating precision and recall. In addition to magnesium, we have identified valproic acid and nitric oxide as chemicals which developed links to migraine. We hypothesize, based on protein annotations, that zinc and retinoic acid may play a role in migraine. The ChemoText repository has promise as a data source for drug discovery
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A critical knowledge pathway to low-carbon, sustainable futures: Integrated understanding of urbanization, urban areas, and carbon
Inequitable distribution of plastic benefits and burdens on economies and public health
Plastic heterogeneously affects social systems – notably human health and local and global economies. Here we discuss illustrative examples of the benefits and burdens of each stage of the plastic lifecycle (e.g., macroplastic production, consumption, recycling). We find the benefits to communities and stakeholders are principally economic, whereas burdens fall largely on human health. Furthermore, the economic benefits of plastic are rarely applied to alleviate or mitigate the health burdens it creates, amplifying the disconnect between who benefits and who is burdened. In some instances, social enterprises in low-wealth areas collect and recycle waste, creating a market for upcycled goods. While such endeavors generate local socioeconomic benefits, they perpetuate a status quo in which the burden of responsibility for waste management falls on downstream communities, rather than on producers who have generated far greater economic benefits. While the traditional cost-benefit analyses that inform decision-making disproportionately weigh economic benefits over the indirect, and often unquantifiable, costs of health burdens, we stress the need to include the health burdens of plastic to all impacted stakeholders across all plastic life stages in policy design. We therefore urge the Intergovernmental Negotiating Committee to consider all available knowledge on the deleterious effects of plastic across the entire plastic lifecycle while drafting the upcoming international global plastic treaty.publishedVersio
Case Report: Possible Links between Sickle Cell Crisis and Pentavalent Antimony
For over 60 years, pentavalent antimony (Sbv) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sbv revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sbv, and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sbv caused the SCC
Pluripotent stem cell assays: Modalities and applications for predictive developmental toxicity
This manuscript provides a review focused on embryonic stem cell-based models and their place within the landscape of alternative developmental toxicity assays. Against the background of the principles of developmental toxicology, the wide diversity of alternative methods using pluripotent stem cells developed in this area over the past half century is reviewed. In order to provide an overview of available models, a systematic scoping review was conducted following a published protocol with inclusion criteria, which were applied to select the assays. Critical aspects including biological domain, readout endpoint, availability of standardized protocols, chemical domain, reproducibility and predictive power of each assay are described in detail, in order to review the applicability and limitations of the platform in general and progress moving forward to implementation. The horizon of innovative routes of promoting regulatory implementation of alternative methods is scanned, and recommendations for further work are given
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