Population PK modelling and simulation based on fluoxetine and norfluoxetine concentrations in milk: a milk concentration-based prediction model

AIMS: Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration-time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk

Gene therapy for carcinoma of the breast: Pro-apoptotic gene therapy

The dysregulation of apoptosis contributes in a variety of ways to the malignant phenotype. It is increasingly recognized that the alteration of pro-apoptotic and anti-apoptotic molecules determines not only escape from mechanisms that control cell cycle and DNA damage, but also endows the cancer cells with the capacity to survive in the presence of a metabolically adverse milieu, to resist the attack of the immune system, to locally invade and survive despite a lack of tissue anchorage, and to evade the otherwise lethal insults induced by drugs and radiotherapy. A multitude of apoptosis mediators has been identified in the past decade, and the roles of several of them in breast cancer have been delineated by studying the clinical correlates of pathologically documented abnormalities. Using this information, attempts are being made to correct the fundamental anomalies at the genetic level. Fundamental to this end are the design of more efficient and selective gene transfer systems, and the employment of complex interventions that are tailored to breast cancer and that are aimed concomitantly towards different components of the redundant regulatory pathways. The combination of such genetic modifications is most likely to be effective when combined with conventional treatments, thus robustly activating several pro-apoptotic pathways

A Tiny Problem with Huge Implications - Nanotech Agents as Enablers or Substitutes for Banned Chemical Weapons: Is a New Treaty Needed?

The underlying thesis of this Article is that while smaller-sized particles and separate nano-sized carriers of known agents are clearly covered by the CWC, nanomimics are not as squarely within the relevant provisions. The bulk of this Article deals with that question. Despite the invitation to woolgather, this Article is limited to the tightest possible analytical approach. Part I begins with definitions of chemical and biological agents within existing treaties, and of nanoproducts, including those existing beyond presently-known technical capabilities, but which are at least reasonably conceivable (“nanobots”). Part II provides an overview of treaty law that is potentially applicable to nanobots. It first examines current treaties that are facially applicable to nanoproducts. Because of the possibility that the “all analogous . . . devices” language of the 1925 Geneva Protocol bans nanobots, the Article examines very closely the origin, application, and meaning of that language. A close inspection necessarily involves considerable discussion of pre-1914 treaties, as well as the battles, weapons, tactics, and legal analyses in World War I, and the mass reaction to them, which resulted in a series of treaties implicating chemical weapons after the war ended. Part II then looks briefly at other treaties, conventions, and doctrines of international law that may impact the use of nanobots. Part III briefly examines current theories regarding good faith treaty interpretation and their implications for the utilization of antique (but not necessarily antiquated) doctrines and documents to interpret current law. Part IV then applies the current treaties to nanoproducts, both existing and potential, in light of the preceding discussion, and then turns to a discussion of whether a new treaty, or modifications or clarifications to existing treaties, are advisable

THE ECONOMIC CALCULUS OF FIELDING AUTONOMOUS FIGHTING VEHICLES COMPLIANT WITH THE LAWS OF ARMED CONFLICT

The U.S. military and others worldwide have undergone a rapid evolution in the numbers, sophistication and lethality of the robotic weaponry that they deploy to the battlefield. The rate of transformation in the field of robotics and weapons technology raises numerous questions about what legal considerations should be made as we approach the step beyond remotely controlled drone weaponry to fully autonomous fighting vehicles as human operated weapons evolve into self-directed warriors