On the modeling of drug induced respiratory depression in the non-steady-state

The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.

[Study protocol of the VISEP study. Response of the SepNet study group]

In the commentary by Zander et al. the authors appear concerned about the methods and results of our, at that time, unpublished sepsis trial evaluating hydroxyethyl starch (HES) and insulin therapy. Unfortunately, the authors' concerns are based on false assumptions about the design, conduct and modes of action of the compounds under investigation. For instance, in our study the HES solution was not used for maintenance of daily fluid requirements, so that the assumption of the authors that this colloid was used "exclusively" is wrong. Moreover, the manufacturer of Hemohes, the HES product we used, gives no cut-off value for creatinine, thus the assumption that this cut-off value was "doubled" in our study is also incorrect. Other claims by the authors such as that lactated solutions cause elevated lactate levels, iatrogenic hyperglycemia and increase O(2) consumption are unfounded. There is no randomized controlled trial supporting such a claim - this claim is neither consistent with our study data nor with any credible published sepsis guidelines or with routine practice worldwide. We fully support open scientific debate. Our study methods and results have now been published after a strict peer-reviewing process and this data is now open to critical and constructive reviewing. However, in our opinion this premature action based on wrong assumptions and containing comments by representatives of pharmaceutical companies does not contribute to a serious, unbiased scientific discourse.

The Chromite Deposits of Stillwater and Sweetgrass Counties, Montana

In writing this report, two objects were kept in mind, (1) to explain, if possible, the origin of the chromite deposits found in Sweetgrass and Stillwater Counties, and (2) to bring up to date all information on these deposits which had thus far been available. The work done consisted of study of the rocks and ores of the area under the microscope, both as thin sections and as polished sections, practically all of which was done at the Montana State School of Mines, during the school year of 1928 - 1929. The rock specimens and much information as to their locations and probable compositions were obtained from Mr. P. F. Minister, of the East Butte Copper Company. United States Geological Survey Bulletin 725-A, Deposits of Chromite in California, Oregon, Washington, and Montana, and the unpublished report on the Chromite deposits of the Boulder River, prepared by Prof. C. H. Clapp of the University of Montana, were frequently referred to and considerable material was drawn from them. The map of the Boulder River area is from Clapp's report.

Research Partnerships for Addressing Global Challenges: Opening Speech

Humankind today is challenged by numerous threats brought about by global change. Climate has been and is being modified by human activities, which calls for mitigation and adaptation measures at an unprecedented scale. Natural resources have been degraded by human development by means of land cover and land use changes, for which protective and restoration measures have to be taken by land users and governments in most countries of the North and South. Low levels of economic development and insufficient policies in most developing countries have led to widespread poverty, which affects nearly half of the world’s population and directly threatens almost one billion people. Finally, uncontrolled economic growth has increased disparities between and within populations and has led to widespread environmental problems in many nations. Generating and sharing knowledge is a key to addressing such global challenges. Knowledge can be used to develop the best solutions and to avoid or repair threats. Research partnerships have proven to be suitable means to bridge the divides and disparities between knowledge societies and developing countries, thereby reducing gaps. Research partnerships are tools for further capacity development and thereby lead to societal empowerment. Institutional settings allowing for research partnerships are needed both in the North and the South, so that the different networks can work together in a long-term enabling environment.