Correlating Bedrock Folds to Higher Rates of Arsenic Detection in Groundwater, Southeast Wisconsin, USA.

Arsenic in private drinking water wells is a significant problem across much of eastern Wisconsin, USA. The release mechanism and stratigraphic distribution of sulfide and iron (hydr)oxide sources of arsenic in bedrock aquifers are well understood for northeastern Wisconsin. However, recent geologic mapping has identified numerous small bedrock folds to the south, and the impact of these geologic structures on local groundwater flow and well contamination has been little studied.

Human altruism, evolution and moral philosophy.

This paper has two central aims. The first is to explore philosophical complications that arise when we move from (i) explaining the evolutionary origins of genetically influenced traits associated with human cooperation and altruism, to (ii) explaining present manifestations of human thought, feeling and behaviour involving cooperation and altruism. While the former need only appeal to causal factors accessible to scientific inquiry, the latter must engage also with a distinctive form of explanation, i.

Discovery of (S,E)-3-(2-fluorophenyl)-N-(1-(3-(pyridin-3-yloxy)phenyl)ethyl)-acrylamide as a potent and efficacious KCNQ2 (Kv7.2) opener for the treatment of neuropathic pain.

Acrylamide (S)-6, a potent and efficacious KCNQ2 (Kv7.2) opener, demonstrated significant activity in two models of neuropathic pain and in the formalin test, suggesting that KCNQ2 openers may be useful in the treatment of neuropathic pain including diabetic neuropathy.

Negotiation: a necessary art for dental practice.

This brief paper explains why the art of negotiation has become far more important for general dental practitioners. It explains that negotiations take place with patients, with practice staff, and with funding agencies such as Primary Care Trusts. It sets out the principles for successful negotiation and gives two examples of how they can be applied.

Safety of concurrent administration of dexrazoxane and doxorubicin in the canine cancer patient.

Doxorubicin may cause a rare but serious cardiotoxicity. Dexrazoxane is a cardioprotectant drug used to reduce the risk of cardiotoxicity in human patients. In this study, 25 tumour-bearing dogs were treated with concurrent doxorubicin and dexrazoxane.

PLEDs: clinical correlates.

Objective: We reviewed our experience in 96 consecutive patients exhibiting periodic lateralized epileptiform discharges (PLEDs) on EEG.

Methods: EEG reports from January 1, 1999 to September 30, 2006 were screened for the term 'PLEDs' and its variants. A retrospective chart review, including examination of neuroimaging and other investigations, was conducted on each patient identified.

Synthesis and KCNQ2 opener activity of N-(1-benzo[1,3]dioxol-5-yl-ethyl, N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl, and N-[1-(2,3-dihydro-1H-indol-5-yl)-ethyl acrylamides.

Bioisosteric replacement studies led to the identification of N-(1-benzo[1,3]dioxol-5-yl-ethyl)-3-(2-chloro-phenyl)-acrylamide ((S)-3) as a highly potent KCNQ2 opener, and 3-(2,6-difluoro-phenyl)-N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl]-acrylamide ((S)-4), and N-[1-(2,3-dihydro-1H-indol-5-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-5) as highly efficacious KCNQ2 openers. In contrast, their respective R enantiomers showed significantly less or no appreciable KCNQ2 opener activity even at the highest concentration tested (10 microM). Because of its high potency and moderate efficacy as well as its convenient synthesis, (+/-)-3 was selected as a reference compound for analyzing efficacies of KCNQ openers in electrophysiology studies.

Ethical pluralism without complementarity.

Grinnell, Bishop, and McCullough (2002) have proposed extending Bohr's notion of complementarity from the realm of quantum physics to that of bioethics, arguing that many ethical disputes cannot in principle be resolved. On this view, we should give up the aim of reaching all-things-considered moral verdicts on a variety of disputed questions, settling instead for a holism of irreducibly complementary perspectives. I discuss a number of difficulties with this proposal, and argue that the desire for inclusiveness that motivates it is properly captured through a different approach to ethical pluralism already familiar in moral philosophy, which does allow for resolution.

(S)-N-[1-(4-cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide is a potent and efficacious KCNQ2 opener which inhibits induced hyperexcitability of rat hippocampal neurons.

(S)-N-[1-(4-Cyclopropylmethyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-2) was identified as a potent and efficacious KCNQ2 opener. This compound demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices, and the inhibition mediated by (S)-2 was reversed by the KCNQ blocker linopirdine.

Fluorine substitution can block CYP3A4 metabolism-dependent inhibition: identification of (S)-N-[1-(4-fluoro-3- morpholin-4-ylphenyl)ethyl]-3- (4-fluorophenyl)acrylamide as an orally bioavailable KCNQ2 opener devoid of CYP3A4 metabolism-dependent inhibition.

The formation of a reactive intermediate was found to be responsible for CYP3A4 metabolism-dependent inhibition (MDI) observed with (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (1). Structure-3A4 MDI relationship studies culminated in the discovery of a difluoro analogue, (S)-N-[1-(4-fluoro-3-morpholin-4-ylphenyl)ethyl]-3-(4-fluoro-phenyl)acrylamide (2), as an orally bioavailable KCNQ2 opener free of CYP3A4 MDI.

Surplus embryos, nonreproductive cloning, and the intend/foresee distinction.

There is, as some public figures have asserted, a real moral difference between creating embryos expressly for medical research and conducting research on embryos that are left over from infertility treatments. To create an embryo intending all along to destroy it is worse. But in the end, it isn't so much worse that we should ban all nonreproductive cloning.

Cost-effectiveness of cardioversion and antiarrhythmic therapy in nonvalvular atrial fibrillation.

Background: Physicians managing patients with nonvalvular atrial fibrillation must consider the risks, benefits, and costs of treatments designed to restore and maintain sinus rhythm compared with those of rate control with antithrombotic prophylaxis.

Objective: To compare the cost-effectiveness of cardioversion, with or without antiarrhythmic agents, with that of rate control plus warfarin or aspirin.

Design: A Markov decision-analytic model was designed to simulate long-term health and economic outcomes.

Quality and customers: Type 2 change in mental health delivery within health care reform.

The traditional separation of mental health and medical programs is problematic because mental health issues are inseparable from the larger medical system. By contrast, a collaborative primary care model of mental health care, augmented and supported by secondary specialty mental health services, has the potential to optimize quality and cost goals while reinforcing health care reform principles. The flexibility of mental health treatment in this delivery structure provides opportunities to customize services according to patient and purchaser expectations.

Regulation of cell growth by recombinant oncostatin M.

Oncostatin M is a novel growth regulator originally isolated from differentiated human histiocytic lymphoma cells and activated T-lymphocytes based on its ability to inhibit the growth of A375 melanoma cells. We report here that oncostatin M is a widely acting regulator which alters the growth and/or morphology of cells derived from a variety of cancer cell types. At picomolar concentrations, recombinant oncostatin M inhibited the growth of 13/24 tumor cell lines.

Bile acid binding to dietary casein: a study in vitro and in vivo.

1. Studies were carried out in vitro using an ultracentrifugation method to quantify bile acid binding to the different components of a Lundh test meal, and to determine what factors influence bile acid binding to one of the components (casein). We validated the ultracentrifugation method by showing good agreement with the equilibrium dialysis method.

Ileal resection: effect of cimetidine and taurine on intrajejunal bile acid precipitation and lipid solubilisation.

We have investigated whether pH-dependent bile acid precipitation limits lipid solubilisation after ileal resection, and whether treatment with cimetidine, or taurine improves solubilisation. Nine ileal resection patients were treated with placebo, cimetidine and taurine in random order for two weeks each. Upper jejunal content was aspirated and pooled according to pH for three hours after a standard Lundh test meal.