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  1. Article: Stateless Persons, Eligible Citizens and Protected Places: The British Nationality Act in Vanuatu.

    Rawlings, Gregory

    20 century British history

    2018  Volume 30, Issue 1, Page(s) 53–80

    Abstract: The British Nationality Act (BNA) of 1948 was designed to provide a form of supranational citizenship to accommodate the separate nationality provisions that were beginning to proliferate as a result of constitutional change within the late empire, ... ...

    Abstract The British Nationality Act (BNA) of 1948 was designed to provide a form of supranational citizenship to accommodate the separate nationality provisions that were beginning to proliferate as a result of constitutional change within the late empire, decolonization and the formation of the Commonwealth. Under the provisions of the BNA, members of the Commonwealth would continue to be unified by transnational forms of citizenship, at least in principle. The Act aimed to cover every political arrangement conceivable in the late empire and early Commonwealth and contributed to the transformation of Great Britain into a multicultural society, by providing the legal vehicle for immigration into the UK in the second half of the twentieth century. However, the BNA had its limits. It could not be applied to territories characterized by constitutional exceptionalism and jurisdictional hybridity. In the Condominium of the New Hebrides, jointly governed by France and Great Britain from 1906 to 1980, the majority of the indigenous population were unable to benefit from the BNA, despite efforts to extend its coverage in all eligible territories. As part of the condominium agreement, the indigenous population were ineligible for any form of citizenship-British, French or New Hebridean-and remained stateless until independence as the Republic of Vanuatu in 1980. This article examines the relationship between indigenous statelessness and the BNA, exploring the implementation, interpretation and extent of the BNA in a territory characterized by constitutional hybridity, compromise and ambiguity. It argues that despite its emphasis on universal commonwealth citizenship, the BNA could not accommodate the diverse political, legal and constitutional diversity that characterized the Dominions, Crown Colonies, protectorates, protected states and condominia that had proliferated under imperial rule and whose legacies continued to inform the possibilities for decolonization and the politics of post-colonial citizenship making.
    Language English
    Publishing date 2018-08-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2077480-1
    ISSN 1477-4674 ; 0955-2359
    ISSN (online) 1477-4674
    ISSN 0955-2359
    DOI 10.1093/tcbh/hwy011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Human plasma cells engineered to secrete bispecifics drive effective

    Hill, Tyler F / Narvekar, Parnal / Asher, Gregory / Camp, Nathan / Thomas, Kerri R / Tasian, Sarah K / Rawlings, David J / James, Richard G

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long- ... ...

    Abstract Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long-term
    Language English
    Publishing date 2023-08-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.24.554523
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: BCR signaling is required for posttransplant lymphoproliferative disease in immunodeficient mice receiving human B cells.

    Zhang, Ting-Ting / Cheng, Rene Yu-Hong / Ott, Andee R / Dahl, Noelle P / Suchland, Emmaline R / Stoffers, Claire M / Asher, Gregory D / Hou, Deyin / Thouvenel, Christopher D / Hill, Tyler F / Rawlings, David J / James, Richard G

    Science translational medicine

    2024  Volume 16, Issue 742, Page(s) eadh8846

    Abstract: Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells ...

    Abstract Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency. We show that a small subset of EBV
    MeSH term(s) Humans ; Animals ; Mice ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/therapy ; Herpesvirus 4, Human ; Lymphoproliferative Disorders/therapy ; Signal Transduction ; B-Lymphocytes
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adh8846
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Fish embryo tests and acute fish toxicity tests are interchangeable in the application of the threshold approach.

    Rawlings, Jane M / Belanger, Scott E / Connors, Kristin A / Carr, Gregory J

    Environmental toxicology and chemistry

    2019  Volume 38, Issue 3, Page(s) 671–681

    Abstract: A database was compiled for algal Organisation for Economic Co-operation and Development (OECD) test guideline 201, for Daphnia magna OECD test guideline 202, for the acute fish toxicity (AFT) OECD test guideline 203, and for the fish embryo toxicity ( ... ...

    Abstract A database was compiled for algal Organisation for Economic Co-operation and Development (OECD) test guideline 201, for Daphnia magna OECD test guideline 202, for the acute fish toxicity (AFT) OECD test guideline 203, and for the fish embryo toxicity (FET) OECD test guideline 236 to assess the suitability and applicability of the FET test in a threshold approach context. In the threshold approach, algal and Daphnia toxicity are assessed first, after which a limit test is conducted at the lower of the 2 toxicity values using fish. If potential fish toxicity is indicated, a full median lethal concentration assay is performed. This tiered testing strategy can significantly reduce the number of fish used in toxicity testing because algae or Daphnia are typically more sensitive than fish. A total of 165 compounds had AFT and FET data available, and of these, 82 had algal and Daphnia acute toxicity data available. Algae and Daphnia were more sensitive 75 to 80% of the time. Fish or FET tests were most sensitive 20 and 16% of the time, respectively, when considered as the sole fish toxicity indicator and 27% of the time when both were considered simultaneously. When fish were the most sensitive trophic level, different compounds were identified as the most toxic in FET and to AFT tests; however, the differences were not so large that they resulted in substantially different outcomes when potencies were binned using the United Nations categories of aquatic toxicity under the Globally Harmonized System for classification and labeling. It is recommended that the FET test could be used to directly replace the AFT test in the threshold approach or could be used as the definitive test if an AFT limit test indicated toxicity potential for a chemical. Environ Toxicol Chem 2019;38:671-681. © 2019 SETAC.
    MeSH term(s) Animals ; Daphnia/drug effects ; Databases, Chemical ; Embryo, Nonmammalian/drug effects ; Fishes/embryology ; Guidelines as Topic ; Organisation for Economic Co-Operation and Development ; Toxicity Tests ; Toxicity Tests, Acute ; Water Pollutants, Chemical/toxicity
    Chemical Substances Water Pollutants, Chemical
    Language English
    Publishing date 2019-02-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 46234-2
    ISSN 1552-8618 ; 0730-7268
    ISSN (online) 1552-8618
    ISSN 0730-7268
    DOI 10.1002/etc.4351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: On the impact of sample size on median lethal concentration estimation in acute fish toxicity testing: Is n = 7/group enough?

    Carr, Gregory J / Bailer, A John / Rawlings, Jane M / Belanger, Scott E

    Environmental toxicology and chemistry

    2018  Volume 37, Issue 6, Page(s) 1565–1578

    Abstract: The fish acute toxicity test method is foundational to aquatic toxicity testing strategies, yet the literature lacks a concise sample size assessment. Although various sources address sample size, historical precedent seems to play a larger role than ... ...

    Abstract The fish acute toxicity test method is foundational to aquatic toxicity testing strategies, yet the literature lacks a concise sample size assessment. Although various sources address sample size, historical precedent seems to play a larger role than objective measures. We present a novel and comprehensive quantification of the effect of sample size on estimation of the median lethal concentration (LC50), covering a wide range of scenarios. The results put into perspective the practical differences across a range of sample sizes, from n = 5/concentration up to n = 23/concentration. We also provide a framework for setting sample size guidance illustrating ways to quantify the performance of LC50 estimation, which can be used to set sample size guidance given reasonably difficult (or worst-case) scenarios. There is a clear benefit to larger sample size studies: they reduce error in the determination of LC50s, and lead to more robust safe environmental concentration determinations, particularly in cases likely to be called worst-case (shallow slope and true LC50 near the edges of the concentration range). Given that the use of well-justified sample sizes is crucial to reducing uncertainty in toxicity estimates, these results lead us to recommend a reconsideration of the current de minimis 7/concentration sample size for critical studies (e.g., studies needed for a chemical registration, which are being tested for the first time, or involving difficult test substances). Environ Toxicol Chem 2018;37:1565-1578. © 2018 SETAC.
    MeSH term(s) Animals ; Fishes ; Sample Size ; Toxicity Tests, Acute/methods ; Water Pollutants, Chemical/toxicity
    Chemical Substances Water Pollutants, Chemical
    Language English
    Publishing date 2018-03-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 46234-2
    ISSN 1552-8618 ; 0730-7268
    ISSN (online) 1552-8618
    ISSN 0730-7268
    DOI 10.1002/etc.4098
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Fish embryo tests and acute fish toxicity tests are interchangeable in the application of the threshold approach

    Rawlings, Jane M / Gregory J. Carr / Kristin A. Connors / Scott E. Belanger

    Environmental toxicology and chemistry. 2019 Mar., v. 38, no. 3

    2019  

    Abstract: A database was compiled for algal Organisation for Economic Co‐operation and Development (OECD) test guideline 201, for Daphnia magna OECD test guideline 202, for the acute fish toxicity (AFT) OECD test guideline 203, and for the fish embryo toxicity ( ... ...

    Abstract A database was compiled for algal Organisation for Economic Co‐operation and Development (OECD) test guideline 201, for Daphnia magna OECD test guideline 202, for the acute fish toxicity (AFT) OECD test guideline 203, and for the fish embryo toxicity (FET) OECD test guideline 236 to assess the suitability and applicability of the FET test in a threshold approach context. In the threshold approach, algal and Daphnia toxicity are assessed first, after which a limit test is conducted at the lower of the 2 toxicity values using fish. If potential fish toxicity is indicated, a full median lethal concentration assay is performed. This tiered testing strategy can significantly reduce the number of fish used in toxicity testing because algae or Daphnia are typically more sensitive than fish. A total of 165 compounds had AFT and FET data available, and of these, 82 had algal and Daphnia acute toxicity data available. Algae and Daphnia were more sensitive 75 to 80% of the time. Fish or FET tests were most sensitive 20 and 16% of the time, respectively, when considered as the sole fish toxicity indicator and 27% of the time when both were considered simultaneously. When fish were the most sensitive trophic level, different compounds were identified as the most toxic in FET and to AFT tests; however, the differences were not so large that they resulted in substantially different outcomes when potencies were binned using the United Nations categories of aquatic toxicity under the Globally Harmonized System for classification and labeling. It is recommended that the FET test could be used to directly replace the AFT test in the threshold approach or could be used as the definitive test if an AFT limit test indicated toxicity potential for a chemical. Environ Toxicol Chem 2019;38:671–681. © 2019 SETAC
    Keywords acute toxicity ; algae ; animal use reduction ; Daphnia magna ; databases ; embryotoxicity ; guidelines ; lethal concentration 50 ; trophic levels ; United Nations
    Language English
    Dates of publication 2019-03
    Size p. 671-681.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 46234-2
    ISSN 1552-8618 ; 0730-7268
    ISSN (online) 1552-8618
    ISSN 0730-7268
    DOI 10.1002/etc.4351
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: The genetic and evolutionary basis of gene expression variation in East Africans.

    Kelly, Derek E / Ramdas, Shweta / Ma, Rong / Rawlings-Goss, Renata A / Grant, Gregory R / Ranciaro, Alessia / Hirbo, Jibril B / Beggs, William / Yeager, Meredith / Chanock, Stephen / Nyambo, Thomas B / Omar, Sabah A / Woldemeskel, Dawit / Belay, Gurja / Li, Hongzhe / Brown, Christopher D / Tishkoff, Sarah A

    Genome biology

    2023  Volume 24, Issue 1, Page(s) 35

    Abstract: Background: Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of ... ...

    Abstract Background: Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania. We assess replication of these QTLs in cohorts of predominantly European ancestry and identify candidate genes under selection in human populations.
    Results: We find the gene regulatory architecture of African and non-African populations is broadly shared, though there is a considerable amount of variation at individual loci across populations. Comparing our analyses to an equivalently sized cohort of European Americans, we find that QTL mapping in Africans improves the detection of expression QTLs and fine-mapping of causal variation. Integrating our QTL scans with signatures of natural selection, we find several genes related to immunity and metabolism that are highly differentiated between Africans and non-Africans, as well as a gene associated with pigmentation.
    Conclusion: Extending QTL mapping studies beyond European ancestry, particularly to diverse indigenous populations, is vital for a complete understanding of the genetic architecture of human traits and can reveal novel functional variation underlying human traits and disease.
    MeSH term(s) Humans ; East African People ; Chromosome Mapping ; Quantitative Trait Loci ; Gene Expression ; Tanzania ; Genetic Variation
    Language English
    Publishing date 2023-02-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-02874-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Are We Hitting the Target? HIV Pre-Exposure Prophylaxis from 2012 to 2020 in the OPERA Cohort.

    Mounzer, Karam C / Fusco, Jennifer S / Hsu, Ricky K / Brunet, Laurence / Vannappagari, Vani / Frost, Kevin R / Shaefer, Mark S / Rinehart, Alex / Rawlings, Keith / Fusco, Gregory P

    AIDS patient care and STDs

    2021  Volume 35, Issue 11, Page(s) 419–427

    Abstract: Preventing HIV transmission is a crucial step in ending the HIV epidemic. Safe and effective pre-exposure prophylaxis (PrEP) has been available in the United States since 2012. We set out to determine if persons at greatest risk for HIV acquisition were ... ...

    Abstract Preventing HIV transmission is a crucial step in ending the HIV epidemic. Safe and effective pre-exposure prophylaxis (PrEP) has been available in the United States since 2012. We set out to determine if persons at greatest risk for HIV acquisition were receiving HIV PrEP. HIV-negative individuals from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort who were prescribed daily PrEP were contrasted with newly diagnosed HIV persons without PrEP use between July 16, 2012 and October 31, 2020 to determine if the PrEP prescriptions reached the populations who were seroconverting. Poisson regression was used to estimate incidence rates of seroconversion to HIV among PrEP initiators, as well as new diagnoses of sexually transmitted infections among both the PrEP group and the newly HIV+ group. Out of the 14,598 PrEP users and 3558 persons newly diagnosed with HIV in OPERA, demographics varied widely. Older individuals, those of non-Black race, men, nonintravenous (IV) drug users, and those with commercial insurance were proportionally overrepresented among those prescribed PrEP compared to persons newly diagnosed with HIV during the same time period. Over 82% of new HIV+ individuals received care in the southern United States compared to only 45% of PrEP users. Seroconversion to HIV among PrEP users was generally uncommon, although more frequent among those who identified as Black individuals, especially in the 13-25 years old age range. In conclusion, providers need innovative programs to better identify, educate, and link those at greatest risk of HIV acquisition, especially young people, women, Black individuals, and IV drug users, to PrEP.
    MeSH term(s) Adolescent ; Adult ; African Americans ; Anti-HIV Agents/therapeutic use ; Female ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Homosexuality, Male ; Humans ; Male ; Pre-Exposure Prophylaxis ; Safe Sex ; Sexually Transmitted Diseases ; United States/epidemiology ; Young Adult
    Chemical Substances Anti-HIV Agents
    Language English
    Publishing date 2021-10-04
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1326868-5
    ISSN 1557-7449 ; 0893-5068 ; 1087-2914
    ISSN (online) 1557-7449
    ISSN 0893-5068 ; 1087-2914
    DOI 10.1089/apc.2021.0064
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  9. Article ; Online: Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

    Appelbaum, Jacob / Price, April E / Oda, Kaori / Zhang, Joy / Leung, Wai-Hang / Tampella, Giacomo / Xia, Dong / So, Pauline Pl / Hilton, Sarah K / Evandy, Claudya / Sarkar, Semanti / Martin, Unja / Krostag, Anne-Rachel / Leonardi, Marissa / Zak, Daniel E / Logan, Rachael / Lewis, Paula / Franke-Welch, Secil / Ngwenyama, Njabulo /
    Fitzgerald, Michael / Tulberg, Niklas / Rawlings-Rhea, Stephanie / Gardner, Rebecca A / Jones, Kyle / Sanabria, Angelica / Crago, William / Timmer, John / Hollands, Andrew / Eckelman, Brendan / Bilic, Sanela / Woodworth, Jim / Lamble, Adam / Gregory, Philip D / Jarjour, Jordan / Pogson, Mark / Gustafson, Joshua A / Astrakhan, Alexander / Jensen, Michael C

    The Journal of clinical investigation

    2024  

    Abstract: Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable, however designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated, drug product for targeting CD33+ tumors called ... ...

    Abstract Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable, however designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated, drug product for targeting CD33+ tumors called dimerization agent regulated immunoreceptor complex (DARIC33). T cell products demonstrated target specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following re-exposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem cell colony forming capacity was not impacted. We benchmarked DARIC33 potency relative to CD19 CAR T cells to estimate a T cell dose for clinical testing. In addition, we integrated in vitro and preclinical in vivo drug concentration thresholds for OFF-ON state transitions, as well as murine and human rapamycin pharmacokinetics, to estimate a clinically applicable rapamycin dosing schedule. A phase 1 DARIC33 trial has been initiated (PLAT-08, NCT05105152), with initial evidence of rapamycin-regulated T cell activation and anti-tumor impact. Our findings provide evidence that the DARIC platform exhibits sensitive regulation and potency needed for clinical application to other important immunotherapy targets.
    Language English
    Publishing date 2024-03-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI162593
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  10. Article ; Online: Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

    Belanger, Scott E / Rawlings, Jane M / Carr, Gregory J

    Environmental toxicology and chemistry

    2013  Volume 32, Issue 8, Page(s) 1768–1783

    Abstract: The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had ... ...

    Abstract The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish.
    MeSH term(s) Animal Testing Alternatives/methods ; Animals ; Embryo, Nonmammalian/drug effects ; Fishes/embryology ; Lethal Dose 50 ; Models, Animal ; Oncorhynchus mykiss ; Pesticides/toxicity ; Regression Analysis ; Reproducibility of Results ; Surface-Active Agents/toxicity ; Toxicity Tests, Acute/methods ; Water Pollutants, Chemical/toxicity
    Chemical Substances Pesticides ; Surface-Active Agents ; Water Pollutants, Chemical
    Language English
    Publishing date 2013-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 46234-2
    ISSN 1552-8618 ; 0730-7268
    ISSN (online) 1552-8618
    ISSN 0730-7268
    DOI 10.1002/etc.2244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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