Tracing the flows of copper and copper alloys in the Early Iron Age societies of the eastern Eurasian steppe

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Closed-loop control of continuous piperacillin delivery: an in silico study

Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described. Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-minute sampling period, targeting a serum piperacillin concentration between 32-64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam. Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches. Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis

Inclusion of a dithiadiazolyl radical in a seemingly non-porous solid

Inclusion of the dithiadiazolyl radical PhCNSSN• into the dynamically porous metallocycle [Cu2(L1)2Cl4], where L1 is the bidentate ligand 1,3-bis(imidazol-1-ylmethyl)-2,4,6- trimethylbenzene, has been achieved by gas phase diffusion. Single crystal X-ray diffraction, powder X-ray diffraction, UV-visible spectroscopy, EPR and SQUID magnetometry studies confirm inclusion of the radical into this seemingly non-porous material, and illustrate the presence of antiferromagnetic coupling between the paramagnetic host and guest species. The radical guest is readily released by heating or by the addition of solvent (CH2Cl2)

Exploring the pharmacokinetics of phenoxymethylpenicillin (Penicillin-V) in adults: a healthy volunteer study

This healthy volunteer study aimed to explore Phenoxymethylpenicillin (Penicillin-V) pharmacokinetics (PK) to support the planning of large, dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentration was determined and a base population PK model were fitted to the data

Experimental Determination of Salinity, Temperature, Growth, and Metabolic Effects on Shell Isotope Chemistry of Mytilus Edulis Collected from Maine and Greenland

To study the effects of temperature, salinity, and life processes (growth rates, size, metabolic effects, and physiological/ genetic effects) on newly precipitated bivalve carbonate, we quantified shell isotopic chemistry of adult and juvenile animals of the intertidal bivalve Mytilus edulis (Blue mussel) collected alive from western Greenland and the central Gulf of Maine and cultured them under controlled conditions. Data for juvenile and adult M. edulis bivalves cultured in this study, and previously by Wanamaker et al. (2006), yielded statistically identical paleotemperature relationships. On the basis of these experiments we have developed a species-specific paleotemperature equation for the bivalve M. edulis [T degrees C = 16.28 (+/- 0.10) -4.57 (+/- 0.15) {delta(18)O(c) VPBD - delta(18)O(w) VSMOW} + 0.06 (+/- 0.06) {delta(18)O(c) VPBD - delta(18)O(w) VSMOW}(2); r(2) = 0.99; N = 323; p \u3c 0.0001]. Compared to the Kim and O\u27Neil (1997) inorganic calcite equation, M. edulis deposits its shell in isotope equilibrium (delta(18)O(calcite)) with ambient water. Carbon isotopes (delta(13)C(calcite)) from sampled shells were substantially more negative than predicted values, indicating an uptake of metabolic carbon into shell carbonate, and delta(13)C(calcite) disequilibrium increased with increasing salinity. Sampled shells of M. edulis showed no significant trends in delta(18)O(calcite) based on size, cultured growth rates, or geographic collection location, suggesting that vital effects do not affect delta(18)O(calcite) in M. edulis. The broad modern and paleogeographic distribution of this bivalve, its abundance during the Holocene, and the lack of an intraspecies physiologic isotope effect demonstrated here make it an ideal nearshore paleoceanographic proxy throughout much of the North Atlantic Ocean

Nasal airflow and odorant transport modeling in patients with chronic rhinosimusitis

Poster presentation at Association for Chemoreception Sciences (ACHEMS) in Sarasota Florida April 25-29, 2007. Introduction: Our on-going clinical project aims to quantify the conductive mechanism contributing toolfactory loss in chronic rhinosinusitis (CRS) patients, in addition to other inflammatory causes(see Yee, et al, 200 and Feng, et al, 203). CRS, a common disease affecting 32 millionAmericans annually, is reportedly associated with at least 15% of all olfactory losses. Airwayconstriction as a result of inflammation or the presence of polyps may limit odor access to thereceptor sites and lead to olfactory dysfunction. As yet, the functional impact of various nasalobstructions as sequelae to CRS and their treatment outcomes have not been successfullyindexed by any existing clinical tools, such as acoustic rhinometry, or rhinomanometry.Computational fluid dynamics (CFD) techniques have shown great promises to simulate nasalairflow and predict odorant delivery rates to the olfactory epithelium based on CT scans. In thisreport, we provide additional support for the hypothesis that the CFD calculation is a betterpredictor of olfactory sensitivity among CRS patients than are conventional methods

Delivering precision antimicrobial therapy through closed-loop control systems

Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients

Assessment of smoking status based on cotinine levels in nasal lavage fluid

Cotinine is a principal metabolite of nicotine with a substantially longer half-life, and cotinine levels in saliva, urine or serum are widely used to validate self-reported smoking status. The nasal cavity and olfactory system are directly exposed to tobacco smoke in smokers and in non-smokers who live with or work around smokers. However, despite the potential for a direct impact of tobacco smoke on the nasal epithelium and olfactory neurons, no prior studies have assessed cotinine levels in nasal mucus. We sought to determine whether cotinine levels in nasal lavage fluid (NLF) would provide a reasonable estimate of smoke exposure. We assayed cotinine using a competitive immunoassay in NLF from 23 smokers, 10 non-smokers exposed to tobacco smoke (ETS) and 60 non-smokers who did not report smoke exposure. NLF cotinine levels were significantly higher in smokers than in non-smokers, regardless of their exposure to ambient tobacco smoke. Cotinine levels in this small group of exposed non-smokers were not significantly different than those of non-exposed non-smokers. A cutoff of 1 ng/ml provided a sensitivity of 91% and a specificity of 99% for smoking status in this sample. Data were consistent with self-reported smoking status, and a cutoff of 1.0 ng/ml NLF cotinine may be used to classify smoking status. While saliva is the most easily obtained body fluid, NLF can be used to provide an objective and precise indication of smoking status and more directly reflects smoke exposure in the nasal and olfactory mucosa