New Zealand place names shared with Central East Polynesia

Place names shared between New Zealand and elsewhere in the Pacific can be used to infer spheres of pre-European Māori contact, a fact used by Best (1917) to support a theory that the ancestors of Māori had sailed as a fleet from a single origin in the Society Islands. The present article is the third in a series that sets out the results of a more open-minded study that surveys shared place names across a wider region. The first two drew attention to the surprisingly high incidence of New Zealand Māori place names shared with southern islands along the Tropic of Capricorn (Crowe 2012), and with the Hawaiian Islands (Crowe 2013). This third article shows how toponyms on several islands in Central East Polynesia manifest similarly strong links to New Zealand, pinpointing the islands on which the strongest links occur. The relevant names are listed by archipelago. Their incidence is also analyzed in the context of other evidence pertaining to contact between each island group and New Zealand, confirming an association not only with the Society, Southern Cook and Austral Islands, but also with three neglected regions, namely the Tuāmotu Archipelago, the Northern Cook Islands and Rapa Iti (Bass Islands)

Effect of nutrition survey 'cleaning criteria' on estimates of malnutrition prevalence and disease burden: secondary data analysis.

Tackling childhood malnutrition is a global health priority. A key indicator is the estimated prevalence of malnutrition, measured by nutrition surveys. Most aspects of survey design are standardised, but data 'cleaning criteria' are not. These aim to exclude extreme values which may represent measurement or data-entry errors. The effect of different cleaning criteria on malnutrition prevalence estimates was unknown. We applied five commonly used data cleaning criteria (WHO 2006; EPI-Info; WHO 1995 fixed; WHO 1995 flexible; SMART) to 21 national Demographic and Health Survey datasets. These included a total of 163,228 children, aged 6-59 months. We focused on wasting (low weight-for-height), a key indicator for treatment programmes. Choice of cleaning criteria had a marked effect: SMART were least inclusive, resulting in the lowest reported malnutrition prevalence, while WHO 2006 were most inclusive, resulting in the highest. Across the 21 countries, the proportion of records excluded was 3 to 5 times greater when using SMART compared to WHO 2006 criteria, resulting in differences in the estimated prevalence of total wasting of between 0.5 and 3.8%, and differences in severe wasting of 0.4-3.9%. The magnitude of difference was associated with the standard deviation of the survey sample, a statistic that can reflect both population heterogeneity and data quality. Using these results to estimate case-loads for treatment programmes resulted in large differences for all countries. Wasting prevalence and caseload estimations are strongly influenced by choice of cleaning criterion. Because key policy and programming decisions depend on these statistics, variations in analytical practice could lead to inconsistent and potentially inappropriate implementation of malnutrition treatment programmes. We therefore call for mandatory reporting of cleaning criteria use so that results can be compared and interpreted appropriately. International consensus is urgently needed regarding choice of criteria to improve the comparability of nutrition survey data

The role of crustal contamination and volatiles in the genesis of the Marathon PGE-copper deposit, Ontario: Constraints from micometre scale LA-ICP-MS lead isotope systematics and PGE distribution

The Marathon deposit is a platinum group element (PGE)-Cu deposit hosted by the Coldwell intrusive complex, located on the north shore of Lake Superior, Ontario. Contradictory models have been proposed for the genesis of the deposit. This paper investigates the relative importance of different ore forming processes responsible for the PGE and Cu enrichment in the deposit and tests these contradictory models. A method has been developed for the precise determination of Pb isotope ratios in solid materials using quadrupole LA-ICP-MS. The advantages of this method are several, including; micrometer-scale spatial resolution, rapid analysis time, and low risk of contamination during sample preparation. Importantly, in samples with low Pb concentrations (∼2 ppm), quadrupole LA-ICP-MS, with N2 added to the nebulizer gas, can yield Pb isotope ratio measurements with a precision (0.2% RSE) that is comparable to LA-MC-ICP-MS. (Abstract shortened by UMI.)Dept. of Earth Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2003 .C76. Source: Masters Abstracts International, Volume: 42-05, page: 1647. Advisers: Iain Samson; Brian Fryer. Thesis (M.Sc.)--University of Windsor (Canada), 2003

Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses

The influence of passage number for Caco2 cell models when evaluating P-gp mediated drug transport

Caco2 cells are a human adenocarcinoma cell line that forms tight junctions and are widely used to examine bidirectional drug transport as well as P-glycoprotein mediated efflux. Unfortunately Caco2 cell lines can be very heterogeneous in nature. Our aim was to improve the Caco2 cell model for determination of P-glycoprotein mediated drug transport. Young passage Caco2 from ATCC had inadequate expression of P-glycoprotein, therefore three approaches were adopted to upregulate Caco2 P-glycoprotein expression to mimic that in vivo; a) incubation of mature Caco2 monolayer with rifampicin, b) prolonged exposure of Caco2 cells to vinblastine (generating the Caco2 VIN line), and c) splitting cells every 7 to 9 days until late passage numbers (over P80) were available. Upon development of the models, P-gp expression and activity was determined using western blotting and bidirectional transport studies of rhodamine123. All four models exhibited P-gp mediated efflux transport for rhodamine123. Incubation with rifampicin did not alter bidirectional transport compared to passage 44 cells. Increased passage number altered P-glycoprotein expression and the efflux ratio increased to 4.7 for passage 80 from 1.4 of passage 44. The highest basolateral to apical transport was observed for both passage 89 Caco2 and the Caco2 VIN model with an efflux ratio of 13 to 14. Western blot images confirmed the increased P-glycoprotein expression of late passage and Caco2 VIN. Caco2 cells are not ready for P-gp related research when first acquired from ATCC (Passage 18). Late passage Caco2 cell monolayers or Caco2 VIN models are needed to determine P-gp mediated efflux transport

Inhibition of P-glycoprotein - Mediated Efflux of Digoxinand Its Metabolites by Macrolide Antibiotics

This study was conducted to determine the rate of P-glycoprotein (P-gp) mediated efflux of digoxin analogues and metabolites, and to assess the effects of macrolide antibiotics on this efflux. Bidirectional transport studies were conducted using our Caco-2 sub clone with high P-gp expression (CLEFF9). HPLC methods were employed to measure drug transport. All digoxin metabolites were P-gp substrates, although digoxin had the greatest efflux ratio. Erythromycin had no effect on the transport of digoxin, maintaining a Basolateral to apical efflux ratio of 14.8, although it did reduce the efflux ratio of dihydrodigoxin and digoxigenin by 34% and 43%, respectively. Azithromycin also had little effect on the transport of digoxin or any of its metabolites. In contrast, clarithromycin and roxithromycin almost eliminated basolateral targeted efflux. Using paclitaxel as a known P-gp substrate, erythromycin demonstrated only partial P-gp inhibitory capacity maintaining an efflux ratio over 100. In contrast, clarithromycin and roxithromycin were 10 fold greater P-gp inhibitors. Clarithromycin and roxithromycin are likely to exhibit drug interactions with digoxin via inhibition of efflux mechanisms. Azithromycin appears to have little influence on P-gp mediated digoxin absorption or excretion and would be the safest macrolide to use concurrently with oral digoxin

Development of a Model for Functional Studies of ABCG2 (Breast Cancer Resistance Protein) Efflux Employing a Standard BeWo Clone (B24)

Human choriocarcinoma-derived BeWo cells express high levels of breast cancer resistance protein (BCRP/ABCG2) with no functional P-glycoprotein (P-gp) (ABCB1) activity, making them a potential model to study bidirectional ABCG2-mediated drug transport. However, the original BeWo clone (B24) available to researchers does not form confluent monolayers with tight junctions required by the model. Our aim was to adapt culture conditions to attempt to generate confluent BeWo monolayers for drug transport studies using the standard B24 clone. BeWo cells (B24; American Type Culture collection [ATCC]) were cultured in six-well plates or polycarbonate millicell inserts in a number of media formulations, growth supplements, and basement membrane substitutes. Cells were examined for confluence by microscopy, and transepithelial electrical resistance (TEER) was measured daily; monolayer permeability was assessed when TEER had stabilized. Optimal growth rates were achieved in culture conditions consisting of Medium 199 (M199) supplemented with epidermal growth factor (EGF; 20 ng/mL), vitamin supplements, and 10% fetal calf serum (FCS) with collagen coating. A TEER of 170 Ω in 0.6 cm2 inserts was achieved 2 weeks after seeding under optimal conditions. The cell-impermeable diffusion marker 5(6) carboxy-2,7dichlorodihydrofluorescein (C-DCDHF) had a permeability coefficient of 3.5 x 10-6 cm/s, indicative of minimal paracellular permeability. ABCG2 expression, as determined by immunoblotting, remained unaffected by confluency. In conclusion, we describe culture conditions for the B24 BeWo clone that facilitate the formation of monolayers with tighter junctions and reduced paracellular transport compared to previously published models. These growth conditions provide a good model of ABCG2-mediated drug transport in a human placental cell line

Teucrium polium: Potential Drug Source for Type 2 Diabetes Mellitus

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed

Pharmacological role of efflux transporters: Clinical implications for medication use during breastfeeding

The World Health Organisation recommends exclusive breastfeeding for the first six months of an infant’s life and in combination with solid food thereafter. This recommendation was introduced based on research showing numerous health benefits of breastfeeding for both the mother and the infant. However, there is always concern regarding the transfer of medications from mother to their breastfed baby via milk. Pharmacokinetic properties of a drug are usually used to predict its transferability into breast milk. Although most drugs are compatible with breastfeeding, cases of toxic drug exposure have been reported. This is thought to be due to active transport mechanisms whereby efflux transporter proteins expressed in the epithelial cells of the mammary gland actively secrete drugs into milk. An example of such efflux transporters including the breast cancer resistance protein which is strongly induced during lactation and this could result in contamination of milk with the substrates of this transporter which may place the suckling infant at risk of toxicity. Furthermore, there is little known about the substrate specificity of most efflux transporters as we have highlighted in this review. There also exists some degree of contradiction between in vivo and in vitro studies which makes it difficult to conclusively predict outcomes and drug-drug interactions