RESUMO
In laboratory experiments, e-cigarettes generated aerosols containing nickel, lead, arsenic, manganese, and other toxic metals. None of the MODs, P ODs, or d-P ODs tested delivered completely metalfree aerosol.
Assuntos
Arsênio , Sistemas Eletrônicos de Liberação de Nicotina , Nicotina , Aerossóis , ManganêsAssuntos
Nefropatias Diabéticas , Etnicidade , Disparidades em Assistência à Saúde , Grupos Raciais , Humanos , Nefropatias Diabéticas/epidemiologia , Etnicidade/legislação & jurisprudência , Etnicidade/estatística & dados numéricos , Acesso aos Serviços de Saúde/legislação & jurisprudência , Acesso aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/legislação & jurisprudência , Disparidades em Assistência à Saúde/estatística & dados numéricos , Grupos Raciais/legislação & jurisprudência , Grupos Raciais/estatística & dados numéricosRESUMO
Many hospital supply chains in the US follow a "stockless" structure, often implemented with the acquisition of new systems promising improved efficiencies and responsiveness. Despite vendor promises, supply chain gains from new technology are often unfulfilled or result in a reduction of performance. A critical component of achieving promised gains is the hospital's ability to accurately and consistently capture hospital inventory use. In practice, recording demand with perfect, 100% accuracy is infeasible, so our models condition on the level of accuracy in a particular hospital department, or point-of-use (POU) inventory location. Similar to previous literature, we consider actual net inventory and recorded net inventory in developing the system performance measures. We develop two models, optimizing either cost or service level, and we assume a periodic-review, base-stock (or par-level) inventory policy with full backordering. In addition to choosing the optimal order-up-to level, we seek the optimal frequency of inventory counts to reconcile inaccurate records. Results from both models provide insights for supply chain managers in the hospital setting, as well as hospital administrators considering the adoption of similar technologies or systems.
Assuntos
Equipamentos e Provisões Hospitalares , Inventários Hospitalares , Comércio , HumanosRESUMO
MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population.