The emergence and decline of the Delaware Indian nation in western Pennsylvania and the Ohio country, 1730--1795

Many past and current generations of historians, anthropologists, and literary writers have acknowledged the existence of a Delaware Indian nation. They, however, have failed to thoroughly understand or address the historical and cultural dynamics that contributed to both the formation and quick decline of this Indian nation. This multidisciplinary study includes the oral traditions and oratory of Delaware Indians, the observances of Moravian missionaries and colonial-revolutionary officials, and contemporary anthropological and historical sources, to construct the building of the Delaware nation during the eighteenth century.;Once decentralized and living in the Delaware River watershed, three phratries or animal tribes (Turtle, Turkey, and Wolf) of Delawares, in response to their unfair treatment at the hands of the Pennsylvania-Iroquois alliance of 1732, moved west to the Allegheny Valley of western Pennsylvania and eventually across the Ohio River into the Muskingum River valley. Western Delawares developed a sense of common cause and weathered the turmoil of imperial conflict between the French and British during the Seven Years\u27 War in western Pennsylvania. A regional identity was greatly enhanced when western Delawares by 1765 separated themselves politically from their eastern kin who remained on the Susquehanna.;This dissertation also considers the creation of a National Council or Lupwaaeenoawuk, the influence of Moravian missionaries, and the importance of visionary leaders, such as Tamaqua, White Eyes, and Captain Pipe---three important factors, imperative to the story of Delaware centralization and nationhood in the Ohio. The stability of a lasting political Delaware nation, however, was undermined by the stress of factionalism in the Great Council as the American Revolution divided Delaware leaders in 1780.;This study will also examine the processes, which led to the fractured state of the Delawares after Washington\u27s Indian War in the Old Northwest Territory and the subsequent Treaty of Greenville that followed in 1795. The story of the Delawares from 1730-1795 demonstrates a dramatic and arduous struggle for autonomy, identity, and political union. In the end, however, the Delaware nation became weakened and broken, driven from the Ohio and forced to migrate west once again

Lithium Regulates Glycogen Synthase Kinase-3β in Human Peripheral Blood Mononuclear Cells: Implication in the Treatment of Bipolar Disorder

Background: Bipolar disorder has been linked to alterations in the multifunctional enzyme glycogen synthase kinase-3β (GSK3β). The mood stabilizer lithium inhibits GSK3β in vitro and in mouse brain, and this is currently the strongest known potential therapeutic target of lithium. We tested whether lithium modified GSK3β in vivo or in vitro in peripheral blood mononuclear cells (PBMCs) from healthy control and bipolar disorder subjects. Methods: The PBMCs were obtained from 23 healthy control subjects, 9 bipolar subjects currently treated with lithium, and 13 lithium-free bipolar subjects. Immunoblot analyses were used to measure the inhibited, serine9-phosphorylated GSK3β. Results: The level of phospho-Ser9-GSK3β in PBMCs was regulated by agents that modified kinases and phosphatases acting on GSK3β and was increased by in vitro lithium treatment. More important, phospho-Ser9-GSK3β levels were eightfold higher in PBMCs from lithium-treated bipolar than healthy control subjects. Conclusions: Signaling pathways regulating serine9-phosphorylation of GSK3β can be studied in human PBMCs. Both in vitro and in vivo therapeutic lithium treatment is associated with a large increase in phospho-Ser9-GSK3β in PBMCs. Therefore, the inhibitory serine9-phosphorylation of GSK3β in human PBMCs may provide a biochemical marker to evaluate the association between GSK3β inhibition and therapeutic responses to lithium treatment

Identifying hypothetical genetic influences on complex disease phenotypes

<p>Abstract</p> <p>Background</p> <p>Statistical interactions between disease-associated loci of complex genetic diseases suggest that genes from these regions are involved in a common mechanism impacting, or impacted by, the disease. The computational problem we address is to discover relationships among genes from these interacting regions that may explain the observed statistical interaction and the role of these genes in the disease phenotype.</p> <p>Results</p> <p>We describe a heuristic algorithm for generating hypothetical gene relationships from loci associated with a complex disease phenotype. This approach, called Prioritizing Disease Genes by Analysis of Common Elements (PDG-ACE), mines biomedical keywords from text descriptions of genes and uses them to relate genes close to disease-associated loci. A keyword common to, and significantly over-represented in, a pair of gene descriptions may represent a preliminary hypothesis about the biological relationship between the genes, and suggest the role the genes play in the disease phenotype.</p> <p>Conclusion</p> <p>Our experimentation shows that the approach finds previously published relationships, while failing to find relationships that don't exist. The results also indicate that the approach is robust to differences in keyword vocabulary. We outline a brief case study in which results from a recently published Type 2 Diabetes association study are used to identify potential hypotheses.</p

Latent Tuberculosis among Persons at Risk for Infection with HIV, Tijuana, Mexico

Interventions that prevent HIV transmission and TB reactivation are needed

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men

CONTEXT: The development of a safe and effective reversible method of male contraception is still an unmet need. OBJECTIVE: Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. DESIGN: Prospective multicentre study. SETTING: Ten study centers. PARTICIPANTS: Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. INTERVENTION: Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. MAIN OUTCOMES MEASURES: Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. RESULTS: Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. CONCLUSIONS: The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high