A bioassay for cyclophosphamide in blood, lung and tumour.

A bioassay has been developed to detect and quantify the concentration of cytotoxic metabolites of cyclophosphamide (CY) in blood, tumour, and lungs of mice. Extracts were made of blood or solid tissues taken from mice given CY and these were used to treat log phase Chinese Hamster V79 cells in culture for up to 24 h. The amount of cell killing was tested by colony formation 7 days later. The effects of incubation time, CY dose, and the time of tissue sampling after CY injection were investigated. The bioassay could detect cytotoxic metabolites in blood after doses as low as 10 mg kg-1 CY given i.p. The half life of these metabolites in blood after giving 400 mg kg-1 i.p. decreased over a 2 h period from 14 to 9 min. The method was then modified to define the pharmacokinetics of CY metabolites in two different types of tumour and in lung. The half life of the cytotoxic metabolites in the lung was longer than in blood, falling from 35 to 11 min over a 2 h period. In tumours, the half lives were longer again, i.e. approximately 61 min. The maximum metabolite levels achieved were similar in the two tumour types, although these differed markedly in their therapeutic response to CY. The bioassay for CY is a relatively simple and rapid procedure, and the extension of its application from body fluids to solid tissues makes it a useful tool in experimental pharmacokinetic studies

Operationalizing risk perception and preparedness behavior research for a multi-hazard context

Increasingly, citizens are being asked to take a more active role in disaster risk reduction (DRR), as decentralization of hazard governance has shifted greater responsibility for hazard preparedness actions onto individuals. Simultaneously, the taxonomy of hazards considered for DRR has expanded to include medical and social crises alongside natural hazards. Risk perception research emerged to support decision-makers with understanding how people characterize and evaluate different hazards to anticipate behavioral response and guide risk communication. Since its inception, the risk perception concept has been incorporated into many behavioral theories, which have been applied to examine preparedness for numerous hazard types. Behavioral theories have had moderate success in predicting or explaining preparedness behaviors; however, they are typically applied to a single hazard type and there is a gap in understanding which theories (if any) are suited for examining multiple hazard types simultaneously. This paper first reviews meta-analyses of behavioral theories to better understand performance. Universal lessons learnt are summarized for survey design. Second, theoretically based preparedness studies for floods, earthquakes, epidemics, and terrorism are reviewed to assess the conceptual requirements for a ‘multi-hazard’ preparedness approach. The development of an online preparedness self-assessment and learning platform is discussed

ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented

Chemical Tuning of Positive and Negative Magnetoresistances, and Superconductivity in 1222-type Ruthenocuprates

High critical-temperature superconductivity and large (colossal) magnetoresistances are two important electronic conducting phenomena found in transition metal oxides. High-Tc materials have applications such as superconducting magnets for MRI and NMR, and magnetoresistive materials may find use in magnetic sensors and spintronic devices. Here we report chemical doping studies of RuSr2(R2-xCex)Cu2O10-d ruthenocuprates which show that a single oxide system can be tuned between superconductivity at high hole dopings and varied magnetoresistive properties at low doping levels. A robust variation of negative magnetoresistance with hole concentration is found in the RuSr2R1.8-xY0.2CexCu2O10-d series, while RuSr2R1.1Ce0.9Cu2O10-d materials show an unprecedented crossover from negative to positive magnetoresistance with rare earth (R) ion radius

Cell kinetic analysis of murine squamous cell carcinomas: a comparison of single versus double labelling using flow cytometry and immunohistochemistry.

The study was originally set up to measure accurate cell kinetic parameters in two murine squamous cell carcinomas (scc) for comparison with radiobiological data on proliferation during radiotherapy. The tumours, AT84 and AT478, were both moderately well differentiated aneuploid scc. In the course of the study, several comparisons of techniques were made in two different centres. This paper reports on the results of those comparisons involving two different detection methods (flow cytometry and immunohistochemistry), single vs double labelling, and in vivo and in vitro labelling, the latter using tissue slices incubated under high pressure oxygen. Pulse labelling studies with bromodeoxyuridine (BrdUrd) showed that the labelling indices (LI) were not significantly different after in vitro or in vivo labelling. In addition, the flow cytometry (FCM) and immunohistochemistry (IHC) methods also gave labelling indices which were not significantly different. Only tumour cells were analysed in these studies by selecting cells on the basis of aneuploidy (FCM) or morphology (IHC). The DNA synthesis time of the tumour cells were analysed by both techniques. For FCM, the Relative Movement method was used (Begg et al., 1985). For IHC, a double labelling method was used, employing BrdUrd and triated thymidine (3H-TdR) administered several hours apart, detected simultaneously using immunoperoxidase and autoradiography, respectively. When both labels were administered in vivo, there was good agreement for Ts between the FCM and IHC methods. Attempts were also made to measure Ts in vitro using both techniques. With double labelling, it was found that cells did not take up the second label, implying a failure of cycle progression. This was confirmed by FCM results, showing no movement of labelled cells through the S-phase, despite an initially high uptake. This could not be influenced by lowering the DNA precursor concentration or by adding foetal calf serum. This indicates that DNA synthesis times are difficult or impossible to measure in vitro in fresh tumour explants. Finally, the double labelling IHC method allowed intratumoural variations of both LI and Ts to be studied. Both parameters were found to vary markedly throughout the tumour volume, particularly for larger tumours (600 mg), giving calculated local potential doubling time values (Tpot) ranging from 1-7 days

The Waipounamu Erosion Surface: questioning the antiquity of the New Zealand land surface and terrestrial fauna and flora

The Waipounamu Erosion Surface is a time-transgressive, nearly planar, wave-cut surface. It is not a peneplain. Formation of the Waipounamu Erosion Surface began in Late Cretaceous time following break-up of Gondwanaland, and continued until earliest Miocene time, during a 60 million year period of widespread tectonic quiescence, thermal subsidence and marine transgression. Sedimentary facies and geomorphological evidence suggest that the erosion surface may have eventually covered the New Zealand subcontinent (Zealandia). We can find no geological evidence to indicate that land areas were continuously present throughout the middle Cenozoic. Important implications of this conclusion are: (1) the New Zealand subcontinent was largely, or entirely, submerged and (2) New Zealand's present terrestrial fauna and flora evolved largely from fortuitous arrivals during the past 22 million years. Thus the modern terrestrial biota may not be descended from archaic ancestors residing on Zealandia when it broke away from Gondwanaland in the Cretaceous, since the terrestrial biota would have been extinguished if this landmass was submerged in Oligocene–Early Miocene time. We conclude that there is insufficient geological basis for assuming that land was continuously present in the New Zealand region through Oligocene to Early Miocene time, and we therefore contemplate the alternative possibility, complete submergence of Zealandia

Effect of Aging on the Reversibility of Pu(IV) Sorption to Goethite

Designing safe remediation and disposal strategies for plutonium (Pu) requires understanding the sorption affinity of Pu for soil minerals. Sorption of Pu(IV) was examined with respect to aging for a goethite system using batch sorption experiments. Sorption of Pu(IV) to iron oxides has been observed to be strong, rapid, and possibly irreversible or hysteretic. These observations may be explained by aging, a surface chemical process happening after initial sorption which causes a change in contaminant surface speciation over time. Measurements of Pu(IV) sorption are often complicated by oxidative leaching of Pu(IV) as Pu(V). Desferrioxamine B (DFOB) is a complexant capable of competing with the proposed strong surface complexes. Additionally, DFOB minimizes oxidative leaching by forming strong Pu(IV)-DFOB complexes, thereby stabilizing Pu(IV) as the dominant aqueous oxidation state. Pu(IV) was reacted in suspensions of 0.1g/L goethite and 10mM NaCl spanning pH 4–7 for various lengths of time (1,6,15,34 and 116 days). Supernatant was replaced with a 1.7µM DFOB solution and, after 34 more days, analyzed for aqueous Pu by liquid scintillation counting. Modeling sorption curves in FITEQL yielded logK values which increased from 0.078 to 0.953 over 116 days, indicating Pu(IV) sorption onto goethite becomes less reversible with aging

A comparison of age-standardised event rates for acute and chronic coronary heart disease in metropolitan and regional/remote Victoria: a retrospective cohort study

Abstract Background Acute and chronic coronary heart disease (CHD) pose different burdens on health-care services and require different prevention and treatment strategies. Trends in acute and chronic CHD event rates can guide service implementation. This study evaluated changes in acute and chronic CHD event rates in metropolitan and regional/remote Victoria. Methods Victorian hospital admitted episodes with a principal diagnosis of acute CHD or chronic CHD were identified from 2005 to 2012. Acute and chronic CHD age-standardised event rates were calculated in metropolitan and regional/remote Victoria. Poisson log-link linear regression was used to estimate annual change in acute and chronic CHD event rates. Results Acute CHD age-standardised event rates decreased annually by 2.9 % (95 % CI, −4.3 to −1.4 %) in metropolitan Victoria and 1.7 % (95 % CI, −3.2 to −0.1 %) in regional/remote Victoria. In comparison, chronic CHD age-standardised event rates increased annually by 4.8 % (95 % CI, +3.0 to +6.5 %) in metropolitan Victoria and 3.1 % (95 % CI, +1.3 to +4.9 %) in regional/remote Victoria. On average, age-standardised event rates for regional/remote Victoria were 30.3 % (95 % CI, 23.5 to 37.2 %) higher for acute CHD and 55.3 % (95 % CI, 47.1 to 63.5 %) higher for chronic CHD compared to metropolitan Victoria from 2005 to 2012. Conclusion Annual decreases in acute CHD age-standardised event rates might reflect improvements in primary prevention, while annual increases in chronic CHD age-standardised event rates suggest a need to improve secondary prevention strategies. Consistently higher acute and chronic CHD age-standardised event rates were evident in regional/remote Victoria compared to metropolitan Victoria from 2005 to 2012