Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients

Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced intensity transplants can also achieve cure, and result in less treatment related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a Phase I/II trial to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24 hour area under the curve (AUC) of approximately 7095 uMmin which represents a 43% increase over the standard total daily AUC dose of 4800 uMmin given by intermittent schedules. DLTs at doses over 8000 uMmin were identified as a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary or other organ toxicies were seen while efficacy appeared to be improved at higher dose levels. Continuous infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy

Resolving Troubled Systemically Important Cross-Border Financial Institutions: Is a New Corporate Organizational Form Required?

This paper explores the advantages of a new financial charter for large, complex, internationally active financial institutions that would address the corporate governance challenges of such organizations, including incentive problems in risk decisions and the complicated corporate and regulatory structures that impede cross-border resolutions. The charter envisions a single entity with broad powers in which the extent and timing of compensation are tied to financial results, senior managers and risk takers form a new risk-bearing stakeholder class, and a home-country-based resolution regime operates for the benefit of all creditors. The proposal is offered 1) to highlight the point that even in the face of a more efficient and effective resolution process, incentives for excessive risk taking will continue unless the costs of risk decisions are internalized by institutions, 2) to suggest another avenue for moving toward a streamlined organizational structure and single global resolution process, and 3) to complement other proposals aimed at preserving a large role for market discipline and firm incentives in a post-reform financial system

The UK demand for steel

The paper suggests a short-run model of the demand for steel that may be used for forecasting future trends. The paper commences with consideration of a long-run model which is estimated using cointegration analysis. An error correction model is then developed to depict the short-run movements to equilibrium. This can be used for the purpose of ex-post forecasting

Zika virus and the nonmicrocephalic fetus: why we should still worry

Zika virus is a mosquito-transmitted flavivirus and was first linked to congenital microcephaly caused by a large outbreak in northeastern Brazil. Although the Zika virus epidemic is now in decline, pregnancies in large parts of the Americas remain at risk because of ongoing transmission and the potential for new outbreaks. This review presents why Zika virus is still a complex and worrisome public health problem with an expanding spectrum of birth defects and how Zika virus and related viruses evade the immune response to injure the fetus. Recent reports indicate that the spectrum of fetal brain and other anomalies associated with Zika virus exposure is broader and more complex than microcephaly alone and includes subtle fetal brain and ocular injuries; thus, the ability to prenatally diagnose fetal injury associated with Zika virus infection remains limited. New studies indicate that Zika virus imparts disproportionate effects on fetal growth with an unusual femur-sparing profile, potentially providing a new approach to identify viral injury to the fetus. Studies to determine the limitations of prenatal and postnatal testing for detection of Zika virus–associated birth defects and long-term neurocognitive deficits are needed to better guide women with a possible infectious exposure. It is also imperative that we investigate why the Zika virus is so adept at infecting the placenta and the fetal brain to better predict other viruses with similar capabilities that may give rise to new epidemics. The efficiency with which the Zika virus evades the early immune response to enable infection of the mother, placenta, and fetus is likely critical for understanding why the infection may either be fulminant or limited. Furthermore, studies suggest that several emerging and related viruses may also cause birth defects, including West Nile virus, which is endemic in many parts of the United States. With mosquito-borne diseases increasing worldwide, there remains an urgent need to better understand the pathogenesis of the Zika virus and related viruses to protect pregnancies and child health

Flexibles Fotolithographisches Prozesscenter (FFP). Teilprojekt: Qualifizierung Modul 6000 Ergebnisbericht

Available from TIB Hannover: FR 5128+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

"What We Breathe Impacts Our Health : Improving Understanding of the Link between Air Pollution and Health"

Air pollution contributes to the premature deaths of millions of people each year around the world, and air quality problems are growing in many developing nations. While past policy efforts have succeeded in reducing particulate matter and trace gases in North America and Europe, adverse health effects are found at even these lower levels of air pollution. Future policy actions will benefit from improved understanding of the interactions and health effects of different chemical species and source categories. Achieving this new understanding requires air pollution scientists and engineers to work increasingly closely with health scientists. In particular, research is needed to better understand the chemical and physical properties of complex air pollutant mixtures, and to use new observations provided by satellites, advanced in situ measurement techniques, and distributed micro monitoring networks, coupled with models, to better characterize air pollution exposure for epidemiological and toxicological research, and to better quantify the effects of specific source sectors and mitigation strategies