BackgroundQuantum dots (QDs) are autofluorescent semiconductor nanocrystals that can be used for in vivo biomedical imaging. However, we know little about their in vivo disposition and health consequences.ObjectivesWe assessed the tissue disposition and pharmacokinetics of QD705 in mice.MethodsWe determined quantitatively the blood and tissue kinetics of QD705 in mice after single intravenous (iv) injection at the dose of 40 pmol for up to 28 days. Inductively coupled plasma–mass spectrometry (ICP-MS) measurement of cadmium was the primary method of quantification of QD705. Fluorescence light microscopy revealed the localization of QD705 in tissues.ResultsPlasma half-life of QD705 in mice was short (18.5 hr), but ICP-MS analyses revealed QD705 persisted and even continued to increase in the spleen, liver, and kidney 28 days after an iv dose. Considerable time-dependent redistribution from body mass to liver and kidney was apparent between 1 and 28 days postdosing. The recoveries at both time points were near 100%; all QD705s reside in the body. Neither fecal nor urinary excretion of QD705 was detected appreciably in 28 days postdosing. Fluorescence microscopy demonstrated deposition of QD705 in the liver, spleen, and kidneys.ConclusionJudging from the continued increase in the liver (29–42% of the administered dose), kidney (1.5–9.2%), and spleen (4.8–5.2%) between 1 and 28 days without any appreciable excretion, QD705 has a very long half-life, potentially weeks or even months, in the body and its health consequences deserve serious consideration.

We conducted pharmacokinetic and toxicology studies on Quantum Dot 705 (QD705) in male ICR mice for up to 6 months after a single intravenous dose. Time-course sacrifices were carried out at 1, 4, and 24 h; 3, 7, 14, and 28 days; and 6 months on groups of six mice per time point. Mass balance studies were also carried out at 24 h, 28 days, and 6 months. Using inductively coupled plasma mass spectrometry, various tissues, urine, and feces were analyzed for cadmium (Cd111), which is a major (46%) component of QD705. On the basis of these experimental studies, a physiologically based pharmacokinetic computer simulation model was developed with excellent predictive capability for the time-dependent kinetic and distributional changes of QD705 in tissues. QD705 persisted and accumulated in the spleen, liver, and kidneys for at least 28 days with little or no disposition but was gradually and partially eliminated by 6 months. Although histological alterations of the spleen, liver, and kidney by light microscopy are unremarkable, investigation using electron microscopy on numerous renal samples revealed definitive mitochondrial alterations in renal tubular epithelial cells at 28 days and 6 months postdosing. Health implications and potential beneficial applications of QD705 are suggested.

A frequent problem in estimating logistic regression models is a failure of the likelihood maximization algorithm to converge. In most cases, this failure is a consequence of data patterns known as complete or quasi-complete separation. For these patterns, the maximum likelihood estimates simply do not exist. In this paper, I examine how and why complete or quasi-complete separation occur, and the effects they produce in output from SAS ® procedures.I then describe and evaluate several possible solutions.

There is evidence indicating that ingestion of arsenic may predispose the development of diabetes mellitus in arsenic-endemic areas in Taiwan. However, the prevalence of diabetes and related vascular diseases in the entire southwestern arseniasis-endemic and nonendemic areas remains to be elucidated. We used the National Health Insurance Database for 1999-2000 to derive the prevalence of non-insulin-dependent diabetes and related vascular diseases by age and sex among residents in southwestern arseniasis-endemic and nonendemic areas in Taiwan. The study included 66,667 residents living in endemic areas and 639,667 in nonendemic areas, all ≥ 25 years of age. The status of diabetes and vascular diseases was ascertained through disease diagnosis and treatment prescription included in the reimbursement claims of clinics and hospitals. The prevalence of non-insulin-dependent diabetes, age-and gender-adjusted to the general population in Taiwan, was 7.5% (95% confidence interval, 7.4-7.7%) in the arseniasis-endemic areas and 3.5% (3.5-3.6%) in the nonendemic areas. Among both diabetics and nondiabetics, higher prevalence of microvascular and macrovascular diseases was observed in arseniasis-endemic than in the nonendemic areas. Age-and gender-adjusted prevalence of microvascular disease in endemic and nonendemic areas was 20.0% and 6.0%, respectively, for diabetics, and 8.6% and 1.0%, respectively, for nondiabetics. The corresponding prevalence of macrovascular disease was 25.3% and 13.7% for diabetics, and 12.3% and 5.5% for nondiabetics. Arsenic has been suggested to increase the risk of non-insulin-dependent diabetes mellitus and its related micro-and macrovascular diseases.