Project description:King Philip II was the father of Alexander the Great. He suffered a notorious penetrating wound by a lance through his leg that was nearly fatal and left him lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977 and 1978 two male skeletons were excavated in the Royal Tombs II and I of Vergina, Greece, respectively. Tomb I also contained another adult (likely a female) and a newborn skeleton. The current view is that Philip II was buried in Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that would indicate lameness. We investigated the skeletal material of Tomb I with modern forensic techniques. The male individual in Tomb I displays a conspicuous case of knee ankylosis that is conclusive evidence of lameness. Right through the overgrowth of the knee, there is a hole. There are no obvious signs that are characteristic of infection and osteomyelitis. This evidence indicates that the injury was likely caused by a severe penetrating wound to the knee, which resulted in an active inflammatory process that stopped years before death. Standard anthropological age-estimation techniques based on dry bone, epiphyseal lines, and tooth analysis gave very wide age ranges for the male, centered around 45 y. The female would be around 18-y-old and the infant would be a newborn. It is concluded that King Philip II, his wife Cleopatra, and their newborn child are the occupants of Tomb I.
Project description:Objectives. To investigate the transfer of marketing knowledge and infrastructure for targeting racial/ethnic minorities from the tobacco to the food and beverage industry in the United States.Methods. We analyzed internal industry documents between April 2018 and April 2019 from the University of California San Francisco Truth Tobacco Industry Documents Library, triangulated with other sources.Results. In the 1980s, Philip Morris Companies purchased General Foods and Kraft Foods and created Kraft General Foods. Through centralized marketing initiatives, Philip Morris Companies directly transferred expertise, personnel, and resources from its tobacco to its food subsidiaries, creating a racial/ethnic minority-targeted food and beverage marketing program modeled on its successful cigarette program. When Philip Morris Companies sold Kraft General Foods in 2007, Kraft General Foods had a "fully integrated" minority marketing program that combined target marketing with racial/ethnic events promotion, racial/ethnic media outreach, and corporate donations to racial/ethnic leadership groups, making it a food industry leader.Conclusions. The tobacco industry directly transferred racial/ethnic minority marketing knowledge and infrastructure to food and beverage companies. Given the substantial growth of food and beverage corporations, their targeting of vulnerable populations, and obesity-related disparities, public policy and community action is needed to address corporate target marketing.
Project description:The cartoon Fidgety Philip, the banner of Western-ADHD diagnosis, depicts a 'restless' child exhibiting hyperactive-behaviors with hyper-arousability and/or hypermotor-restlessness (H-behaviors) during sitting. To overcome the gaps between differential diagnostic considerations and modern computing methodologies, we have developed a non-interpretative, neutral pictogram-guided phenotyping language (PG-PL) for describing body-segment movements during sitting (Journal of Psychiatric Research). To develop the PG-PL, seven research assistants annotated three original Fidgety Philip cartoons. Their annotations were analyzed with descriptive statistics. To review the PG-PL's performance, the same seven research assistants annotated 12 snapshots with free hand annotations, followed by using the PG-PL, each time in randomized sequence and on two separate occasions. After achieving satisfactory inter-observer agreements, the PG-PL annotation software was used for reviewing videos where the same seven research assistants annotated 12 one-minute long video clips. The video clip annotations were finally used to develop a machine learning algorithm for automated movement detection (Journal of Psychiatric Research). These data together demonstrate the value of the PG-PL for manually annotating human movement patterns. Researchers are able to reuse the data and the first version of the machine learning algorithm to further develop and refine the algorithm for differentiating movement patterns.
Project description:The identification of sites on receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and modes of pharmacology for target modulation. Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numerous advantages, as well as caveats (e.g., flat structure-activity relationships, species differences, "molecular switches"), have been identified. For multiple receptors and proteins, numerous examples have been described where unprecedented levels of selectivity are achieved along with improved physiochemical properties. While not a panacea, these novel approaches represent exciting opportunities for tool compound development to probe the pharmacology and therapeutic potential of discrete molecular targets, as well as new medicines. In this Perspective, in commemoration of the 2013 Philip S. Portoghese Medicinal Chemistry Lectureship ( Lindsley , C. W. Adventures in allosteric drug discovery . Presented at the 246th National Meeting of the American Chemical Society, Indianapolis, IN, September 10, 2013 ; The 2013 Portoghese Lectureship ), several vignettes of drug discovery campaigns targeting novel allosteric mechanisms will be recounted, along with lessons learned and guidelines that have emerged for successful lead optimization.
Project description:BackgroundIn 1996 Massachusetts proposed regulations that would require tobacco companies to disclose information about the ingredients in their products on a by-brand basis. This paper examines the strategies employed by Philip Morris to stop these regulations from being implemented.Methods and findingWe used previously secret tobacco industry documents and published literature to examine the activities of the tobacco companies after the regulations were proposed. Philip Morris hired a public relations firm to establish a coalition that was instructed to oppose the regulations by linking them to other industrial sectors (the slippery slope) and stating they would damage the state's economy. Philip Morris also retained a polling firm to test the popularity of specific arguments against ingredient disclosure and developed a strategic plan for opposing similar regulations in Vermont.ConclusionTobacco companies have historically used third parties to form coalitions to oppose ingredient disclosure regulations. These coalitions have had success preventing regulations from being implemented after they are initially proposed by creating the appearance of local opposition. With countries around the world currently implementing ingredient disclosure regulations in the WHO Framework Convention on Tobacco, governments and regulatory agencies should be aware of the political strategies that the tobacco companies have used to create the impression of popular opposition to these measures.
Project description:In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations.We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as "Project MIX." Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect.The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.