Policy and Social Factors Influencing Diabetes among Pima Indians in Arizona, USA

The Pima Indians have the highest rate of type 2 diabetes in the world. While biomedical studies have identified a genetic variable associated with the high prevalence of diabetes among Pima Indians, genetics is only one factor that encompasses an individual’s risk for developing a disease. Information on the social factors relating to the development of type 2 diabetes amongst this population is necessary. The purpose of this analysis is to review policy, social and historical factors associated with diabetes among Pima Indians. Governmental policies have affected this population’s ability to eat a diet native to their culture. For example, the damming of the Gila River in the early 1920s resulted in diet and lifestyle changes, reducing traditional low fat, high fiber intake and physical activity, among the Pima population. U.S. Department of Agriculture (USDA) policies in place in the 1970s and 1980s did not allow Native Americans, the Pima included, to get farm help such as agricultural loans in times of need. These policies led to many Pima finding sedentary jobs, if they could find work at all, and adopting unhealthy lifestyles. While genetic factors have shown to be important predictors of diabetes incidence, the historical and social factors that changed US Pima Indians’ lifestyles are significant factors which have contributed to the high prevalence of diabetes among this group. In order to address the high rates of diabetes among the Pima Indians, it is vital that emphasis be placed upon culturally appropriate interventions. U.S. government agencies, tribal leaders, and community elders would benefit from working together to establish healthier food sources, encourage physical activity, and utilize existing community networks to spread information on diabetes prevention and management practices. Future studies on diabetes among Pima Indians would include more policy, social and historical factors, develop programs with reflection of these factors, and evaluate the programs. Keywords: Pima Indians, type 2 diabetes, Native American policies, social factors, US

Worm Epidemics in Wireless Adhoc Networks

A dramatic increase in the number of computing devices with wireless communication capability has resulted in the emergence of a new class of computer worms which specifically target such devices. The most striking feature of these worms is that they do not require Internet connectivity for their propagation but can spread directly from device to device using a short-range radio communication technology, such as WiFi or Bluetooth. In this paper, we develop a new model for epidemic spreading of these worms and investigate their spreading in wireless ad hoc networks via extensive Monte Carlo simulations. Our studies show that the threshold behaviour and dynamics of worm epidemics in these networks are greatly affected by a combination of spatial and temporal correlations which characterize these networks, and are significantly different from the previously studied epidemics in the Internet

Generation of a Kupffer Cell-evading Adenovirus for Systemic and Liver-directed Gene Transfer

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated \u3e10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to escape Kupffer cell uptake as evidenced by producing no Kupffer cell death in vivo, not requiring predosing in vivo, and being phagocytosed less efficiently by macrophages in vitro compared to Ad5. When tested as a helper-dependent adenovirus (Ad) vector, Ad5/6 mediated higher luciferase and factor IX transgene expression than either helper-dependent adenoviral 5 (HD-Ad5) or HD-Ad6 vectors. These data suggest that the Ad5/6 hexon-chimera evades Kupffer cells and may have utility for systemic and liver-directed therapies

Generation of a Kupffer Cell-evading Adenovirus for Systemic and Liver-directed Gene Transfer

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated \u3e10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to escape Kupffer cell uptake as evidenced by producing no Kupffer cell death in vivo, not requiring predosing in vivo, and being phagocytosed less efficiently by macrophages in vitro compared to Ad5. When tested as a helper-dependent adenovirus (Ad) vec- tor, Ad5/6 mediated higher luciferase and factor IX trans- gene expression than either helper-dependent adenoviral 5 (HD-Ad5) or HD-Ad6 vectors. These data suggest that the Ad5/6 hexon-chimera evades Kupffer cells and may have utility for systemic and liver-directed therapies

Species D Adenoviruses as Oncolytics against B-cell Cancers

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we mined the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers. Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers for their ability to infect, replicate in, and kill these cells. Select viruses were also tested against B-cell cancer xenografts in immunodeficient mice. Results: Species D adenoviruses mediated most robust killing against a range of B-cell cancer cell lines, against primary patient marginal zone lymphoma cells, and against primary patient CD138þ myeloma cells in vitro. When injected into xenografts in vivo, single treatment with select species D viruses Ad26 and Ad45 delayed lymphoma growth. Conclusions: Relatively unstudied species Dadenoviruses have a unique ability to infect and replicate in B-cell cancers as compared with other adenovirus species. These data suggest these viruses have unique biology in B cells and support translation of novel species D adenoviruses as oncolytics against B-cell cancers

Oxidation of Thiols to Disulfides using an Environmentally “Green” Organocatalyst and New Mechanistic Insights

The selective oxidation of thiols to disulfides is an area of great importance in the areas of materials and medicinal chemistry research. The production of polymers, rubber, pharmaceuticals, and the folding of proteins in biological systems all rely on the formation of disulfide bonds. Herein, we introduce a stoichiometric and electrocatalytic method for the oxidation of various pharmaceutically and biologically relevant thiols into their respective disulfides in more environmentally benign solvents such as water and alcohol solvents. The scope of the transformation was evaluated and a detailed mechanistic study involving control experiments, experimental kinetic studies, and computational investigations led to new insights into how the oxidation takes place via an unusual anionic process

Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy

"Meaning" as a sociological concept: A review of the modeling, mapping, and simulation of the communication of knowledge and meaning

The development of discursive knowledge presumes the communication of meaning as analytically different from the communication of information. Knowledge can then be considered as a meaning which makes a difference. Whereas the communication of information is studied in the information sciences and scientometrics, the communication of meaning has been central to Luhmann's attempts to make the theory of autopoiesis relevant for sociology. Analytical techniques such as semantic maps and the simulation of anticipatory systems enable us to operationalize the distinctions which Luhmann proposed as relevant to the elaboration of Husserl's "horizons of meaning" in empirical research: interactions among communications, the organization of meaning in instantiations, and the self-organization of interhuman communication in terms of symbolically generalized media such as truth, love, and power. Horizons of meaning, however, remain uncertain orders of expectations, and one should caution against reification from the meta-biological perspective of systems theory

The Road to Servomechanisms: The Influence of Cybernetics on Hayek from the Sensory Order to the Social Order

This paper explores the ways in which c ybernetics influenced the works of F. A. Hayek from the late 1940s onwar d. It shows that the concept of negative feedback, borrowed from cybernetics, was central to Hayek's attempt of giving an explanation of the principle to the emergence of human purposive behavior. Next, the paper discusses Ha yek's later uses of cybernetic ideas in his works on the spontaneous formation of social orders. Finally, Hayek's view on the appropriate scope of the use of cybernetics is considered