A case study of the relationship between public relations and collective bargaining at General Electric.

Thesis (M.S.)--Boston Universit

Maroon Archaeology Beyond the Americas: A View From Kenya

Archaeological research on Maroons—that is, runaway slaves—has been largely confined to the Americas. This essay advocates a more global approach. It specifically uses two runaway slave communities in 19th-century coastal Kenya to rethink prominent interpretive themes in the field, including “Africanisms,” Maroons’ connections to indigenous groups, and Maroon group cohesion and identity. This article’s analysis demonstrates that the comparisons enabled by a more globalized perspective benefit the field. Instead of eliding historical and cultural context, these comparisons support the development of more localized and historically specific understandings of individual runaway slave communities both in Kenya and throughout the New World

A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype.

Three founder transgenic mice were generated with a 108 kb human genomic fragment containing the entire autosomal dominant polycystic kidney disease (ADPKD) gene, PKD1, plus the tuberous sclerosis gene, TSC2. Two lines were established (TPK1 and TPK3) each with approximately 30 copies of the transgene. Both lines produced full-length PKD1 mRNA and polycystin-1 protein that was developmentally regulated, similar to the endogenous pattern, with expression during renal embryogenesis and neonatal life, markedly reduced at the conclusion of renal development. Tuberin expression was limited to the brain. Transgenic animals from both lines (and the TPK2 founder animal) often displayed a renal cystic phenotype, typically consisting of multiple microcysts, mainly of glomerular origin. Hepatic cysts and bile duct proliferation, characteristic of ADPKD, were also seen. All animals with two copies of the transgenic chromosome developed cysts and, in total, 48 of the 100 transgenic animals displayed a cystic phenotype. To test the functionality of the transgene, animals were bred with the Pkd1(del34) knockout mouse. Both transgenic lines rescued the embryonically lethal Pkd1(del34/del34) phenotype, demonstrating that human polycystin-1 can complement for loss of the endogenous protein. The rescued animals were viable into adulthood, although more than half developed hepatic cystic disease in later life, similar to the phenotype of older Pkd1(del34/+) animals. The TPK mice have defined a minimal area that appropriately expresses human PKD1. Furthermore, this model indicates that over-expression of normal PKD1 can elicit a disease phenotype, suggesting that the level of polycystin-1 expression may be relevant in the human disease

Absent otoacoustic emissions predict otitis media in young Aboriginal children: A birth cohort study in Aboriginal and non-Aboriginal children in an arid zone of Western Australia

Background: Otitis media (OM) is the most common paediatric illness for which antibiotics are prescribed. In Australian Aboriginal children OM is frequently asymptomatic and starts at a younger age, is more common and more likely to result in hearing loss than in non-Aboriginal children. Absent transient evoked otoacoustic emissions (TEOAEs) may predict subsequent risk of OM. Methods: 100 Aboriginal and 180 non-Aboriginal children in a semi-arid zone of Western Australia were followed regularly from birth to age 2 years. Tympanometry was conducted at routine field follow-up from age 3 months. Routine clinical examination by an ENT specialist was to be done 3 times and hearing assessment by an audiologist twice. TEOAEs were measured at ages <1 and 1-2 months. Cox proportional hazards model was used to investigate the association between absent TEOAEs and subsequent risk of OM. Results: At routine ENT specialist clinics, OM was detected in 55% of 184 examinations in Aboriginal children and 26% of 392 examinations in non-Aboriginal children; peak prevalence was 72% at age 5-9 months in Aboriginal children and 40% at 10-14 months in non-Aboriginal children. Moderate-severe hearing loss was present in 32% of 47 Aboriginal children and 7% of 120 non-Aboriginal children aged 12 months or more. TEOAE responses were present in 90% (46/51) of Aboriginal children and 99% (120/121) of non-Aboriginal children aged <1 month and in 62% (21/ 34) and 93% (108/116), respectively, in Aboriginal and non-Aboriginal children at age 1-2 months. Aboriginal children who failed TEOAE at age 1-2 months were 2.6 times more likely to develop OM subsequently than those who passed. Overall prevalence of type B tympanograms at field follow-up was 50% (n = 78) in Aboriginal children and 20% (n = 95) in non-Aboriginal children. Conclusion: The burden of middle ear disease is high in all children, but particularly in Aboriginal children, one-third of whom suffer from moderate-severe hearing loss. In view of the frequently silent nature of OM, every opportunity must be taken to screen for OM. Measurement of TEOAEs at age 1-2 months to identify children at risk of developing OM should be evaluated in a routine health service setting

Pharmacokinetics and Metabolism of 2-Aminothiazoles with Antiprion Activity in Mice

PURPOSE: To discover drugs lowering PrP(Sc) in prion-infected cultured neuronal cells that achieve high concentrations in brain to test in mouse models of prion disease and then treat people with these fatal diseases. METHODS: We tested 2-AMT analogs for EC(50) and PK after a 40 mg/kg single dose and 40–210 mg/kg/day doses for 3 days. We calculated plasma and brain AUC, ratio of AUC/EC(50) after dosing. We reasoned that compounds with high AUC/EC(50) ratios should be good candidates going forward. RESULTS: We evaluated 27 2-AMTs in single-dose and 10 in 3-day PK studies, of which IND24 and IND81 were selected for testing in mouse models of prion disease. They had high concentrations in brain after oral dosing. Absolute bioavailability ranged from 27–40%. AUC/EC(50) ratios after 3 days were >100 (total) and 48–113 (unbound). Stability in liver microsomes ranged from 30–>60 min. Ring hydroxylated metabolites were observed in microsomes. Neither was a substrate for the MDR1 transporter. CONCLUSIONS: IND24 and IND81 are active in vitro and show high AUC/EC(50) ratios (total and unbound) in plasma and brain. These will be evaluated in mouse models of prion disease