Two-axis bend measurement with Bragg gratings in multicore optical fiber

We describe what is to our knowledge the first use of fiber Bragg gratings written into three separate cores of a multicore fiber for two-axis curvature measurement. The gratings act as independent, but isothermal, fiber strain gauges for which local curvature determines the difference in strain between cores, permitting temperature-independent bend measurement. (C) 2003 Optical Society of America

Stereoselective pharmacokinetics of stable isotope (+/-)-[13C]-pantoprazole: Implications for a rapid screening phenotype test of CYP2C19 activity

AIMS: We have previously shown that the (±)-[(13) C]-pantoprazole breath test is a promising noninvasive probe of CYP2C19 activity. As part of that trial, plasma, breath test indices and CYP2C19 (*2, *3, and *17) genotype were collected. Here, we examined whether [(13) C]-pantoprazole exhibits enantioselective pharmacokinetics and whether this enantioselectivity is correlated with indices of breath test. METHODS: Plasma (-)- and (+)-[(13) C]-pantoprazole that were measured using a chiral HPLC were compared between CYP2C19 genotypes and correlated with breath test indices. RESULTS: The AUC( 0-∞) of (+)-[(13) C]-pantoprazole in PM (*2/*2, n = 4) was 10.1- and 5.6-fold higher that EM (*1/*1or *17, n = 10) and IM (*1/*2or *3, n = 10) of CYP2C19, respectively (P < 0.001). The AUC( 0-∞) of (-)-[(13) C]-pantoprazole only significantly differed between PMs and EMs (1.98-fold; P = 0.05). The AUC( 0-∞) ratio of (+)-/(-)-[(13) C]-pantoprazole was 3.45, 0.77, and 0.67 in PM, IM, and EM genotypes, respectively. Breath test index, delta over baseline show significant correlation with AUC( 0-∞) of (+)-[(13) C]-pantoprazole (Pearson's r = 0.62; P < 0.001). CONCLUSIONS: [(13) C]-pantoprazole exhibits enantioselective elimination. (+)-[(13) C]-pantoprazole is more dependent on CYP2C19 metabolic status and may serve as a more attractive probe of CYP2C19 activity than (-)-[(13) C]-pantoprazole or the racemic mixture

Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach

Myopathy is a group of muscle diseases that can be induced or exacerbated by drug-drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine-simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System

The effects of climatic warming on the phenology of Arctic plants and their principal herbivore

There is mounting evidence that many plants and animals may be unable to adjust the timing of their various life cycle events rapidly enough to adjust to predicted rates of climate change. For example, the close synchronisation between bud-burst and herbivore emergence may be disrupted by increased temperatures. However, many experimental studies demonstrating these effects have only used short term temperature manipulations, despite the possibility that strong selection pressure could lead to rapid adaptation to a changing climate over several years. This study therefore investigated whether phenological synchrony between plants and their herbivores was disrupted after five years of simulated climate change. A series of warming chambers was set up across the forest-tundra ecotone in Arctic Sweden. The chambers increased temperatures relative to control plots in line with average predictions from climate change models. The warming chambers did not affect the timing of snow melt, suggesting that hydrological conditions were broadly similar in warming chambers and control plots. Plants growing in areas with a late-melting snow pack showed accelerated development and growth in comparison with plants in early-melting areas, so that plants in all areas completed development at about the same time. However, invertebrate herbivores were more closely synchronised to their host plants in areas where immature foliage was only available for a short period of time. Experimental warming advanced the onset of leaf development and also increased the area of leaf tissue available to herbivores. However, phenological synchrony between invertebrate herbivores and their host plants was not affected by warming, as the lag between leaf emergence and the onset of herbivory was similar in warming chambers and control plots. This suggests that herbivores may be able to respond relatively rapidly to changes in host plant phenology. However, elevated temperatures were associated with an increase in defoliation, with potentially severe consequences for the birch forests of northern Fennoscandia

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Background: Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy. Methods: Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment. Results: Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed. Conclusion: Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes

Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy

To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration’s role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist’s role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy

Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100

Background: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. Methods: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3–5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. Results: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10−8OR=3.3) and in the cumulative dose model (P=4.7 × 10−8HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3–5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037OR=2.4). Conclusions: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials

Estimating the annual distribution of monarch butterflies in Canada over 16 years using citizen science data

Monarch butterflies (Danaus plexippus, Linnaeus, 1758) are comprised of two migratory populations separated by the Rocky Mountains and are renowned for their long-distance movements among the United States, Canada, and Mexico. Both populations have declined over several decades across North America prompting all three countries to evaluate conservation efforts. Monitoring monarch distribution and abundance is a necessary aspect of ongoing management in Canada where they are a species at risk. We used presence-only data from two citizen science data sets to estimate the annual breeding distribution of monarch butterflies in Canada between 2000 and 2015. Monarch breeding distribution in Canada varied widely among years owing to natural variation, and when considering the upper 95% of the probability of occurrence, the annual mean breeding distribution in Canada was 484 943 km(2) (min: 173 449 km(2); max: 1 425 835 km(2)). The area of occurrence was approximately an order of magnitude larger in eastern Canada than in western Canada. Habitat restoration for monarch butterflies in Canada should prioritize productive habitats in southern Ontario where monarchs occur annually and, therefore, likely contribute most to the long-term viability of monarchs in eastern North America. Overall, our assessment sets the geographic context to develop successful management strategies for monarchs in Canada.Liber Ero Postdoctoral Fellowship; University Research Chair from the University of GuelphOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting

This manuscript provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward

Gene expression profiles of 4‐hydroxy‐N‐desmethyl‐tamoxifen (endoxifen)‐ and 4‐hydroxy‐tamoxifen (4OHTAM)‐treated human breast cancer cells determined by CDNA microarray analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109798/1/cptclpt2004192.pd