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  1. Article ; Online: Identifying potential high-risk zones for land-derived plastic litter to marine megafauna and key habitats within the North Atlantic.

    Garrard, Samantha L / Clark, James R / Martin, Nicola / Nelms, Sarah E / Botterell, Zara L R / Cole, Matthew / Coppock, Rachel L / Galloway, Tamara S / Green, Dannielle S / Jones, Megan / Lindeque, Pennie K / Tillin, Heidi M / Beaumont, Nicola J

    The Science of the total environment

    2024  Volume 922, Page(s) 171282

    Abstract: The pervasive use of plastic in modern society has led to plastic litter becoming ubiquitous within the ocean. Land-based sources of plastic litter are thought to account for the majority of plastic pollution in the marine environment, with plastic bags, ...

    Abstract The pervasive use of plastic in modern society has led to plastic litter becoming ubiquitous within the ocean. Land-based sources of plastic litter are thought to account for the majority of plastic pollution in the marine environment, with plastic bags, bottles, wrappers, food containers and cutlery among the most common items found. In the marine environment, plastic is a transboundary pollutant, with the potential to cause damage far beyond the political borders from where it originated, making the management of this global pollutant particularly complex. In this study, the risks of land-derived plastic litter (LDPL) to major groups of marine megafauna - seabirds, cetaceans, pinnipeds, elasmobranchs, turtles, sirenians, tuna and billfish - and a selection of productive and biodiverse biogenic habitats - coral reefs, mangroves, seagrass, saltmarsh and kelp beds - were analysed using a Spatial Risk Assessment approach. The approach combines metrics for vulnerability (mechanism of harm for megafauna group or habitat), hazard (plastic abundance) and exposure (distribution of group or habitat). Several potential high-risk zones (HRZs) across the North Atlantic were highlighted, including the Azores, the UK, the French and US Atlantic coasts, and the US Gulf of Mexico. Whilst much of the modelled LDPL driving risk in the UK originated from domestic sources, in other HRZs, such as the Azores archipelago and the US Gulf of Mexico, plastic originated almost exclusively from external (non-domestic) sources. LDPL from Caribbean islands - some of the largest generators of marine plastic pollution in the dataset of river plastic emissions used in the study - was noted as a significant input to HRZs across both sides of the Atlantic. These findings highlight the potential of Spatial Risk Assessment analyses to determine the location of HRZs and understand where plastic debris monitoring and management should be prioritised, enabling more efficient deployment of interventions and mitigation measures.
    MeSH term(s) Environmental Monitoring ; Plastics ; Ecosystem ; Environmental Pollution ; Environmental Pollutants ; Waste Products/analysis
    Chemical Substances Plastics ; Environmental Pollutants ; Waste Products
    Language English
    Publishing date 2024-02-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2024.171282
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The development and evaluation of dose-prediction tools for allopurinol therapy (Easy-Allo tools).

    Wright, Daniel F B / Hishe, Hailemichael Z / Stocker, Sophie L / Dalbeth, Nicola / Horne, Anne / Drake, Jill / Haslett, Janine / Phipps-Green, Amanda J / Merriman, Tony R / Stamp, Lisa K

    British journal of clinical pharmacology

    2024  Volume 90, Issue 5, Page(s) 1268–1279

    Abstract: Aims: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient ... ...

    Abstract Aims: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient dose-escalation strategies. The aim of this research was to develop and externally evaluate allopurinol dosing tools, one for use when the pre-urate-lowering therapy serum urate is known (Easy-Allo1) and one for when it is not known (Easy-Allo2).
    Methods: A revised population pharmacokinetic-pharmacodynamic model was developed using data from 653 people with gout. Maintenance doses to achieve the serum urate target of <0.36 mmol L
    Results: Allopurinol doses were predicted by total body weight, baseline urate, ethnicity and creatinine clearance. Easy-Allo1 produced unbiased and suitably precise dose predictions (MPE 2 mg day
    Conclusions: The Easy-Allo tools provide a guide to the allopurinol maintenance dose requirement to achieve the serum urate target of <0.36 mmol L
    MeSH term(s) Allopurinol/administration & dosage ; Allopurinol/pharmacokinetics ; Humans ; Gout/drug therapy ; Gout/blood ; Gout Suppressants/administration & dosage ; Gout Suppressants/pharmacokinetics ; Uric Acid/blood ; Dose-Response Relationship, Drug ; Models, Biological ; Male ; Female ; Middle Aged ; Aged ; Adult ; Drug Dosage Calculations ; Computer Simulation
    Chemical Substances Allopurinol (63CZ7GJN5I) ; Gout Suppressants ; Uric Acid (268B43MJ25)
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.16005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The evolving role of medical geneticists in the era of gene therapy: An urgency to prepare.

    Vockley, Jerry / Brunetti-Pierri, Nicola / Chung, Wendy K / Clarke, Angus J / Gold, Nina / Green, Robert C / Kagan, Stephen / Moroz, Tara / Schaaf, Christian P / Schulz, Martin / De Baere, Elfride

    Genetics in medicine : official journal of the American College of Medical Genetics

    2023  Volume 25, Issue 4, Page(s) 100022

    MeSH term(s) Humans ; Genetics, Medical ; Surveys and Questionnaires ; Genetic Therapy ; Physicians
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1455352-1
    ISSN 1530-0366 ; 1098-3600
    ISSN (online) 1530-0366
    ISSN 1098-3600
    DOI 10.1016/j.gim.2023.100022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Response to Beretich and Beretich.

    Vockley, Jerry / Brunetti-Pierri, Nicola / Chung, Wendy K / Clarke, Angus J / Gold, Nina / Green, Robert C / Kagan, Stephen / Moroz, Tara / Schaaf, Christian P / Schulz, Martin / De Baere, Elfride

    Genetics in medicine : official journal of the American College of Medical Genetics

    2023  Volume 25, Issue 10, Page(s) 100903

    Language English
    Publishing date 2023-05-25
    Publishing country United States
    Document type Letter
    ZDB-ID 1455352-1
    ISSN 1530-0366 ; 1098-3600
    ISSN (online) 1530-0366
    ISSN 1098-3600
    DOI 10.1016/j.gim.2023.100903
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.

    Melillo, Nicola / Scotcher, Daniel / Kenna, J Gerry / Green, Claudia / Hines, Catherine D G / Laitinen, Iina / Hockings, Paul D / Ogungbenro, Kayode / Gunwhy, Ebony R / Sourbron, Steven / Waterton, John C / Schuetz, Gunnar / Galetin, Aleksandra

    Pharmaceutics

    2023  Volume 15, Issue 3

    Abstract: ... modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (k ...

    Abstract Gadoxetate, a magnetic resonance imaging (MRI) contrast agent, is a substrate of organic-anion-transporting polypeptide 1B1 and multidrug resistance-associated protein 2. Six drugs, with varying degrees of transporter inhibition, were used to assess gadoxetate dynamic contrast enhanced MRI biomarkers for transporter inhibition in rats. Prospective prediction of changes in gadoxetate systemic and liver AUC (AUCR), resulting from transporter modulation, were performed by physiologically-based pharmacokinetic (PBPK) modelling. A tracer-kinetic model was used to estimate rate constants for hepatic uptake (k
    Language English
    Publishing date 2023-03-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15030896
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Impact of Chronic Multi-Generational Exposure to an Environmentally Relevant Atrazine Concentration on Testicular Development and Function in Mice.

    Kolaitis, Nicola D / Finger, Bethany J / Merriner, D Jo / Nguyen, Joseph / Houston, Brendan J / O'Bryan, Moira K / Stringer, Jessica M / Zerafa, Nadeen / Nguyen, Ngoc / Hutt, Karla J / Tarulli, Gerard A / Green, Mark P

    Cells

    2023  Volume 12, Issue 4

    Abstract: A common herbicide, atrazine, is associated with poor health. Atrazine acts as an endocrine disruptor at supra-environmental levels. Little research, however, has been conducted regarding chronic exposure to environmental atrazine concentrations across ... ...

    Abstract A common herbicide, atrazine, is associated with poor health. Atrazine acts as an endocrine disruptor at supra-environmental levels. Little research, however, has been conducted regarding chronic exposure to environmental atrazine concentrations across generations. This study utilized comprehensive endpoint measures to investigate the effects of chronic exposure to a conservative atrazine concentration (0.02 ng/mL), measured in Australian waterways, on male mice fertility across two generations. Mice were exposed through the maternal line, from the pre-conception period and through the F1 and F2 generations until three or six months of age. Atrazine did not impact sperm function, testicular morphology nor germ cell parameters but did alter the expression of steroidogenic genes in the F1, down-regulating the expression of
    MeSH term(s) Male ; Mice ; Animals ; Atrazine/pharmacology ; Australia ; Semen ; Herbicides/pharmacology ; Testis
    Chemical Substances Atrazine (QJA9M5H4IM) ; Herbicides
    Language English
    Publishing date 2023-02-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12040648
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The impact of genetic variability in urate transporters on oxypurinol pharmacokinetics.

    Hishe, Hailemichael Z / Stocker, Sophie L / Stamp, Lisa K / Dalbeth, Nicola / Merriman, Tony R / Phipps-Green, Amanda / Wright, Daniel F B

    Clinical and translational science

    2022  Volume 16, Issue 3, Page(s) 422–428

    Abstract: The genetic determinants of the allopurinol dose-concentration relationship have not been extensively studied. We aimed to clarify what factors, including genetic variation in urate transporters, influence oxypurinol pharmacokinetics (PKs). A population ... ...

    Abstract The genetic determinants of the allopurinol dose-concentration relationship have not been extensively studied. We aimed to clarify what factors, including genetic variation in urate transporters, influence oxypurinol pharmacokinetics (PKs). A population PK model for oxypurinol was developed with NONMEM (version 7.3). The influence of urate transporter genetic variants for ABCG2 (rs2231142 and rs10011796), SLC2A9/GLUT9 (rs11942223), SLC17A1/NPT1 (rs1183201), SLC22A12/URAT1 (rs3825018), SLC22A11/OAT4 (rs17300741), and ABCC4/MRP4 (rs4148500), as well as other participant factors on oxypurinol PKs was assessed. Data from 325 people with gout were available. The presence of the T allele for ABCG2 (rs2231142) and SLC17A1/NPT1 (rs1183201) was associated with a 24% and 22% increase in oxypurinol clearance, respectively, in univariate analysis. This effect was not significant in the multivariate analysis. In the final model, oxypurinol PKs were predicted by creatinine clearance, diuretic use, ethnicity, and body weight. We have found that genetic variability in the transporters examined does not appear to influence oxypurinol PKs.
    MeSH term(s) Humans ; Oxypurinol/pharmacokinetics ; Uric Acid ; Gout/drug therapy ; Gout/genetics ; Allopurinol/pharmacokinetics ; Organic Anion Transporters/genetics ; Organic Cation Transport Proteins/genetics ; Glucose Transport Proteins, Facilitative/genetics
    Chemical Substances Oxypurinol (G97OZE5068) ; Uric Acid (268B43MJ25) ; urate transporter ; Allopurinol (63CZ7GJN5I) ; SLC22A12 protein, human ; Organic Anion Transporters ; Organic Cation Transport Proteins ; SLC2A9 protein, human ; Glucose Transport Proteins, Facilitative
    Language English
    Publishing date 2022-11-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2433157-0
    ISSN 1752-8062 ; 1752-8054
    ISSN (online) 1752-8062
    ISSN 1752-8054
    DOI 10.1111/cts.13460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: An allopurinol adherence tool using plasma oxypurinol concentrations.

    Smith-Diaz, Natalia / Stocker, Sophie L / Stamp, Lisa K / Dalbeth, Nicola / Phipps-Green, Amanda J / Merriman, Tony R / Wright, Daniel F B

    British journal of clinical pharmacology

    2022  Volume 89, Issue 7, Page(s) 1956–1964

    Abstract: Aims: This study aimed to develop and evaluate an allopurinol adherence tool based on steady-state oxypurinol plasma concentrations, allopurinol's active metabolite.: Methods: Plasma oxypurinol concentrations were simulated stochastically from an ... ...

    Abstract Aims: This study aimed to develop and evaluate an allopurinol adherence tool based on steady-state oxypurinol plasma concentrations, allopurinol's active metabolite.
    Methods: Plasma oxypurinol concentrations were simulated stochastically from an oxypurinol pharmacokinetic model for allopurinol doses of 100-800 mg daily, accounting for differences in renal function, diuretic use and ethnicity. For each scenario, the 20th percentile for peak and trough concentrations defined the adherence threshold, below which imperfect adherence was assumed. Predictive performance was evaluated using both simulated low adherence and against data from 146 individuals with paired oxypurinol plasma concentrations and adherence measures. Sensitivity and specificity (S&S), negative and positive predictive values (NPV, PPV) and receiver operating characteristic (ROC) area under the curve (AUC) were determined. The predictive performance of the tool was evaluated using adherence data from an external study (CKD-FIX).
    Results: The allopurinol adherence tool produced S&S values for trough thresholds of 89-98% and 76-84%, respectively, and 90%-98% and 76-83% for peak thresholds. PPV and NPV were 79-84% and 88-94%, respectively, for trough and 80-85% and 89-98%, respectively, for peak concentrations. The ROC AUC values ranged from 0.84 to 0.88 and from 0.86 to 0.89 for trough and peak concentrations, respectively. S&S values for the external evaluation were found to be 75.8% and 86.5%, respectively, producing an ROC AUC of 0.8113.
    Conclusion: A tool to identify people with gout who require additional support to maintain adherence using plasma oxypurinol concentrations was developed and evaluated. The predictive performance of the tool is suitable for adherence screening in clinical trials and may have utility in some clinical practice settings.
    MeSH term(s) Humans ; Allopurinol/pharmacokinetics ; Oxypurinol ; Gout Suppressants/pharmacokinetics ; Tool Use Behavior ; Gout/drug therapy
    Chemical Substances Allopurinol (63CZ7GJN5I) ; Oxypurinol (G97OZE5068) ; Gout Suppressants
    Language English
    Publishing date 2022-09-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 188974-6
    ISSN 1365-2125 ; 0306-5251 ; 0264-3774
    ISSN (online) 1365-2125
    ISSN 0306-5251 ; 0264-3774
    DOI 10.1111/bcp.15516
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Is repeat serum urate testing superior to a single test to predict incident gout over time?

    Stewart, Sarah / Phipps-Green, Amanda / Gamble, Greg D / Stamp, Lisa K / Taylor, William J / Neogi, Tuhina / Merriman, Tony R / Dalbeth, Nicola

    PloS one

    2022  Volume 17, Issue 2, Page(s) e0263175

    Abstract: Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These ... ...

    Abstract Elevated serum urate is the most important causal risk factor for developing gout. However, in longitudinal cohort studies, a small proportion of people with normal urate levels develop gout and the majority of those with high urate levels do not. These observations may be due to subsequent variations in serum urate over time. Our analysis examined whether single or repeat testing of serum urate more accurately predicts incident gout over time. Individual participant data from three publicly-available cohorts were included. Data from paired serum urate measures 3-5 years apart, followed by an assessment of gout incidence 5-6 years from the second urate measure were used to calculate the predictive ability of four measures of serum urate on incident gout: the first measure, the second measure, the average of the two measures, and the highest of the two measures. Participants with prevalent gout prior to the second measure were excluded. Receiver operator characteristic (ROC) curves and area under the curve (AUC) statistics were computed to compare the four measures. A total of 16,017 participants were included across the three cohorts, with a mean follow-up from the first serum urate test of 9.3 years (range 8.9-10.1 years). Overall, there was a small increase in the mean serum urate between the first and second measures (322 μmol/L (5.42 mg/dL) vs. 340 μmol/L (5.71 mg/dL), P<0.001) which were a mean of 3.5 years apart, but the first and second measures were highly correlated (r = 0.81, P<0.001). No differences were observed in the predictive ability of incident gout between the four measures of serum urate measurement with ROC curve AUC statistics ranging between 0.81 (95% confidence intervals: 0.78-0.84) and 0.84 (95% confidence intervals: 0.81-0.87). These data show that repeat serum urate testing is not superior to a single measure of serum urate for prediction of incident gout over approximately one decade.
    MeSH term(s) Adult ; Area Under Curve ; Female ; Gout/diagnosis ; Gout/epidemiology ; Humans ; Incidence ; Longitudinal Studies ; Male ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; Uric Acid/blood
    Chemical Substances Uric Acid (268B43MJ25)
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0263175
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  10. Article ; Online: Association of rs9939609 in FTO with BMI among Polynesian peoples living in Aotearoa New Zealand and other Pacific nations.

    Krishnan, Mohanraj / Phipps-Green, Amanda / Russell, Emily M / Major, Tanya J / Cadzow, Murray / Stamp, Lisa K / Dalbeth, Nicola / Hindmarsh, Jennie Harré / Qasim, Muhammad / Watson, Huti / Liu, Shuwei / Carlson, Jenna C / Minster, Ryan L / Hawley, Nicola L / Naseri, Take / Reupena, Muagututi'a Sefuiva / Deka, Ranjan / McGarvey, Stephen T / Merriman, Tony R /
    Murphy, Rinki / Weeks, Daniel E

    Journal of human genetics

    2023  Volume 68, Issue 7, Page(s) 463–468

    Abstract: The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In ... ...

    Abstract The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Māori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa. We did not observe statistically significant association within each separate Polynesian subgroup. Bayesian meta-analysis of the Aotearoa New Zealand Polynesian and Samoan samples resulted in a posterior mean effect size estimate of +0.21 kg/m
    MeSH term(s) Humans ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics ; Bayes Theorem ; Body Mass Index ; Genetic Predisposition to Disease ; Maori People/genetics ; New Zealand ; Pacific Island People/genetics ; Polymorphism, Single Nucleotide
    Chemical Substances Alpha-Ketoglutarate-Dependent Dioxygenase FTO (EC 1.14.11.33) ; FTO protein, human (EC 1.14.11.33)
    Language English
    Publishing date 2023-03-02
    Publishing country England
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 1425192-9
    ISSN 1435-232X ; 1434-5161
    ISSN (online) 1435-232X
    ISSN 1434-5161
    DOI 10.1038/s10038-023-01141-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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