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1.
Epidemics ; 47: 100773, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781911

ABSTRACT

Tracking pathogen transmissibility during infectious disease outbreaks is essential for assessing the effectiveness of public health measures and planning future control strategies. A key measure of transmissibility is the time-dependent reproduction number, which has been estimated in real-time during outbreaks of a range of pathogens from disease incidence time series data. While commonly used approaches for estimating the time-dependent reproduction number can be reliable when disease incidence is recorded frequently, such incidence data are often aggregated temporally (for example, numbers of cases may be reported weekly rather than daily). As we show, commonly used methods for estimating transmissibility can be unreliable when the timescale of transmission is shorter than the timescale of data recording. To address this, here we develop a simulation-based approach involving Approximate Bayesian Computation for estimating the time-dependent reproduction number from temporally aggregated disease incidence time series data. We first use a simulated dataset representative of a situation in which daily disease incidence data are unavailable and only weekly summary values are reported, demonstrating that our method provides accurate estimates of the time-dependent reproduction number under such circumstances. We then apply our method to two outbreak datasets consisting of weekly influenza case numbers in 2019-20 and 2022-23 in Wales (in the United Kingdom). Our simple-to-use approach will allow accurate estimates of time-dependent reproduction numbers to be obtained from temporally aggregated data during future infectious disease outbreaks.


Subject(s)
Basic Reproduction Number , Bayes Theorem , Disease Outbreaks , Influenza, Human , Humans , Incidence , Influenza, Human/epidemiology , Influenza, Human/transmission , Disease Outbreaks/statistics & numerical data , Basic Reproduction Number/statistics & numerical data , Time Factors , Computer Simulation , Wales/epidemiology , Epidemiological Models
2.
Opt Express ; 31(11): 17848-17860, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37381508

ABSTRACT

Spectrally incoherent laser pulses with sufficiently large fractional bandwidth are in demand for the mitigation of laser-plasma instabilities occurring in high-energy laser-target interactions. Here, we modeled, implemented, and optimized a dual-stage high-energy optical parametric amplifier for broadband, spectrally incoherent pulses in the near-infrared. The amplifier delivers close to 400 mJ of signal energy through noncollinear parametric interaction of 100-nJ-scale broadband, spectrally incoherent seed pulses near 1053 nm with a narrowband high-energy pump operating at 526.5 nm. Mitigation strategies for high-frequency spatial modulations in the amplified signal caused by index inhomogeneities in the Nd:YLF rods of the pump laser are explored and discussed in detail.

3.
J Dairy Sci ; 105(4): 3559-3573, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35094853

ABSTRACT

Bovine viral diarrhea (BVD) is endemic in the United Kingdom and causes major economic losses. Control is largely voluntary for individual farmers and is likely to be influenced by psychosocial factors, such as altruism, trust, and psychological proximity (feeling close) to relevant "others," such as farmers, veterinarians, the government, and their cows. These psychosocial factors (factors with both psychological and social aspects) are important determinants of how people make decisions related to their own health, many of which have not been studied in the context of infectious disease control by farmers. Farmer psychosocial profiles were investigated using multiple validated measures in an observational survey of 475 UK cattle farmers using the capability, opportunity, motivation-behavior (COM-B) framework. Farmers were clustered by their BVD control practices using latent class analysis. Farmers were split into 5 BVD control behavior classes, which were tested for associations with the psychosocial and COM-B factors using multinomial logistic regression, with doing nothing as the baseline class. Farmers who were controlling disease both for themselves and others were more likely to do something to control BVD (e.g., test, vaccinate). Farmers who did not trust other farmers, had high psychological capability (knowledge and understanding of how to control disease), and had high physical opportunity (time and money to control disease) were more likely to have a closed, separate herd and test. Farmers who did not trust other farmers were also more likely to undertake many prevention strategies with an open herd. Farmers with high automatic motivation (habits and emotions) and reflective motivation (decisions and goals) were more likely to vaccinate and test, alone or in combination with other controls. Farmers with high psychological proximity (feeling of closeness) to their veterinarian were more likely to undertake many prevention strategies in an open herd. Farmers with high psychological proximity to dairy farmers and low psychological proximity to beef farmers were more likely to keep their herd closed and separate and test or vaccinate and test. Farmers who had a lot of trust in other farmers and invested in them, rather than keeping everything for themselves, were more likely to be careful introducing new stock and test. In conclusion, farmer psychosocial factors were associated with strategies for BVD control in UK cattle farmers. Psychological proximity to veterinarians was a novel factor associated with proactive BVD control and was more important than the more extensively investigated trust. These findings highlight the importance of a close veterinarian-farmer relationship and are important for promoting effective BVD control by farmers, which has implications for successful nationwide BVD control and eradication schemes.


Subject(s)
Bovine Virus Diarrhea-Mucosal Disease , Cattle Diseases , Diarrhea Viruses, Bovine Viral , Veterinarians , Animals , Bovine Virus Diarrhea-Mucosal Disease/epidemiology , Bovine Virus Diarrhea-Mucosal Disease/prevention & control , Cattle , Cattle Diseases/prevention & control , Diarrhea/veterinary , Farmers/psychology , Female , Humans , Motivation
4.
Opt Express ; 28(1): 451-471, 2020 Jan 06.
Article in English | MEDLINE | ID: mdl-32118971

ABSTRACT

We study and demonstrate the efficient parametric amplification of spectrally incoherent broadband nanosecond pulses to high energies. Signals composed of mutually incoherent monochromatic lines or amplified spontaneous emission are amplified in a sequence of optical parametric amplifiers pumped at 526.5 nm, with the last amplifier set in a collinear geometry. This configuration results in 70% conversion efficiency from the pump to the combined signal and idler, with a combined energy reaching 400 mJ and an optical spectrum extending over 60 nm around 1053 nm. The spatial, spectral, and temporal properties of the amplified waves are investigated. The demonstrated high conversion efficiency, spectral incoherence, and large bandwidth open the way to a new generation of high-energy, solid-state laser drivers that mitigate laser-plasma instabilities and laser-beam imprint via enhanced spectral bandwidth.

5.
Opt Express ; 25(22): 26802-26814, 2017 Oct 30.
Article in English | MEDLINE | ID: mdl-29092165

ABSTRACT

We describe a parametric-amplification-based front end for seeding high-energy Nd:glass laser systems. The front end delivers up to 200 mJ by parametric amplification in 2.5-ns flat-in-time pulses tunable over more than 15 nm. Spectral tunability over a range larger than what is typically achieved by laser media at similar energy levels is implemented to investigate cross-beam energy transfer in multibeam target experiments. The front-end operation is simulated to explain the amplified signal's sensitivity to the input pump and signal. A large variety of amplified waveforms are generated by closed-loop pulse shaping. Various properties and limitations of this front end are discussed.

6.
Environ Pollut ; 228: 297-304, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28551560

ABSTRACT

Garden centres frequently market nectar- and pollen-rich ornamental plants as "pollinator-friendly", however these plants are often treated with pesticides during their production. There is little information on the nature of pesticide residues present at the point of purchase and whether these plants may actually pose a threat to, rather than benefit, the health of pollinating insects. Using mass spectrometry analyses, this study screened leaves from 29 different 'bee-friendly' plants for 8 insecticides and 16 fungicides commonly used in ornamental production. Only two plants (a Narcissus and a Salvia variety) did not contain any pesticide and 23 plants contained more than one pesticide, with some species containing mixtures of 7 (Ageratum houstonianum) and 10 (Erica carnea) different agrochemicals. Neonicotinoid insecticides were detected in more than 70% of the analysed plants, and chlorpyrifos and pyrethroid insecticides were found in 10% and 7% of plants respectively. Boscalid, spiroxamine and DMI-fungicides were detected in 40% of plants. Pollen samples collected from 18 different plants contained a total of 13 different pesticides. Systemic compounds were detected in pollen samples at similar concentrations to those in leaves. However, some contact (chlorpyrifos) and localised penetrant pesticides (iprodione, pyroclastrobin and prochloraz) were also detected in pollen, likely arising from direct contamination during spraying. The neonicotinoids thiamethoxam, clothianidin and imidacloprid and the organophosphate chlorpyrifos were present in pollen at concentrations between 6.9 and 81 ng/g and at levels that overlap with those known to cause harm to bees. The net effect on pollinators of buying plants that are a rich source of forage for them but simultaneously risk exposing them to a cocktail of pesticides is not clear. Gardeners who wish to gain the benefits without the risks should seek uncontaminated plants by growing their own from seed, plant-swapping or by buying plants from an organic nursery.


Subject(s)
Environmental Monitoring , Insecta/drug effects , Pesticide Residues/analysis , Agrochemicals/analysis , Animals , Bees , Fungicides, Industrial/analysis , Gardening , Guanidines/analysis , Imidazoles/analysis , Insecticides/analysis , Neonicotinoids , Nitro Compounds/analysis , Oxazines/analysis , Pesticides/analysis , Plant Nectar/chemistry , Pollen/chemistry , Pollination/drug effects , Seeds/chemistry , Thiamethoxam , Thiazoles/analysis
7.
Rev Sci Instrum ; 87(5): 053511, 2016 05.
Article in English | MEDLINE | ID: mdl-27250427

ABSTRACT

A timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the ultraviolet light from each beam into a single photodetector.

8.
Proc Biol Sci ; 282(1813): 20151180, 2015 Aug 22.
Article in English | MEDLINE | ID: mdl-26290075

ABSTRACT

Depression is a major public health concern worldwide. There is evidence that social support and befriending influence mental health, and an improved understanding of the social processes that drive depression has the potential to bring significant public health benefits. We investigate transmission of mood on a social network of adolescents, allowing flexibility in our model by making no prior assumption as to whether it is low mood or healthy mood that spreads. Here, we show that while depression does not spread, healthy mood among friends is associated with significantly reduced risk of developing and increased chance of recovering from depression. We found that this spreading of healthy mood can be captured using a non-linear complex contagion model. Having sufficient friends with healthy mood can halve the probability of developing, or double the probability of recovering from, depression over a 6-12-month period on an adolescent social network. Our results suggest that promotion of friendship between adolescents can reduce both incidence and prevalence of depression.


Subject(s)
Affect , Depression/epidemiology , Friends/psychology , Social Support , Adolescent , Depression/etiology , Female , Humans , Male , Models, Psychological
9.
Mol Immunol ; 67(2 Pt A): 28-45, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25911943

ABSTRACT

The therapeutic utility of antibodies and their derivatives is achieved by various means. The FDA has approved several targeted antibodies that disrupt signaling of various growth factor receptors for the treatment of a number of cancers. Rituximab, and other anti-CD20 monoclonal antibodies are active in B cell malignancies. As more experience has been gained with anti-CD20 monoclonal antibodies, the multifactorial nature of their anti-tumor mechanisms has emerged. Other targeted antibodies function to dampen inhibitory checkpoints. These checkpoint inhibitors have recently achieved dramatic results in several cancers, including melanoma. These and related antibodies continue to be investigated in the clinical and pre-clinical settings. Novel antibody structures that target two or more antigens have also made their way into clinical use. Tumor targeted antibodies can also be conjugated to chemo- or radiotherapeutic agents, or catalytic toxins, as a means to deliver toxic payloads to cancer cells. Here we provide a review of these mechanisms and a discussion of their relevance to current and future clinical applications.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy/methods , Neoplasms/therapy , Antibodies, Monoclonal/immunology , Antigens, CD20/immunology , Antigens, CD20/metabolism , CTLA-4 Antigen/immunology , CTLA-4 Antigen/metabolism , ErbB Receptors/immunology , ErbB Receptors/metabolism , Humans , Immunotherapy/trends , Neoplasms/immunology , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Receptor, ErbB-2/immunology , Receptor, ErbB-2/metabolism , Treatment Outcome
10.
Mar Pollut Bull ; 95(2): 610-7, 2015 Jun 30.
Article in English | MEDLINE | ID: mdl-25746199

ABSTRACT

Intersex, the appearance of female characteristics in male gonads, has been identified in several aquatic species. It is a widespread phenomenon in populations of the bivalve, Scrobicularia plana, from the southwest coast of the U.K. Genes previously identified as differentially expressed (ferritin, testicular haploid expressed gene, THEG, proliferating cell nuclear antigen, PCNA; receptor activated protein kinase C, RACK; cytochrome B, CYB; and cytochrome c oxidase 1, COX1) in intersex clams relative to normal male clams, were selected for characterisation and an environmental survey of the Channel region. Transcripts were significantly differentially expressed at sites with varying intersex incidence and contaminant burdens. Significant correlations between specific gene expressions, key contaminants and sampling locations have been identified, though no single gene was associated with intersex incidence. The results highlight the difficulty in understanding the intersex phenomenon in molluscs where there is still a lack of knowledge on the control of normal reproduction.


Subject(s)
Bivalvia/metabolism , Environmental Monitoring/methods , Water Pollutants, Chemical/metabolism , Animals , Biomarkers/metabolism , Bivalvia/genetics , Disorders of Sex Development , Environment , Female , Gene Expression/drug effects , Gene Expression/physiology , Humans , Male , Testis/metabolism , Transcriptome , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
11.
Opt Express ; 23(26): 33116-29, 2015 Dec 28.
Article in English | MEDLINE | ID: mdl-26831979

ABSTRACT

The concept of spectral phase diversity is proposed and applied to the temporal characterization of optical pulses. The experimental trace is composed of the measured power of a plurality of ancillary optical pulses derived from the pulse under test by adding known amounts of chromatic dispersion. The spectral phase of the pulse under test is retrieved by minimizing the error between the experimental trace and a trace calculated using the known optical spectrum and diagnostic parameters. An assembly composed of splitters and dispersive delay fibers has been used to generate 64 ancillary pulses whose instantaneous power can be detected in a single shot with a high-bandwidth photodiode and oscilloscope. The diagnostic is experimentally shown to accurately characterize pulses from a chirped-pulse-amplification system when its stretcher is detuned from the position for optimal recompression. Pulse-shape reconstruction for pulses shorter than the photodetection impulse response has been demonstrated. Various investigations of the performance with respect to the number of ancillary pulses and the range of chromatic dispersion generated in the diagnostic are presented.

12.
Br J Cancer ; 110(12): 2829-36, 2014 Jun 10.
Article in English | MEDLINE | ID: mdl-24867688

ABSTRACT

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.


Subject(s)
Early Detection of Cancer/economics , Early Detection of Cancer/methods , Patient Selection , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Aged , Cost-Benefit Analysis , England , General Practitioners , Humans , Male , Mass Screening/economics , Mass Screening/methods , Middle Aged , Prostatic Neoplasms/mortality , Research Design , Wales
13.
Chemosphere ; 69(1): 1-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17582461

ABSTRACT

Contamination of freshwater environments by estrogenic compounds has led to concern over potential impacts on invertebrate species. The uptake of the environmental estrogen 17beta-estradiol (E2) by the freshwater bivalve Dreissena polymorpha and the nature of estrogenic substances in tissues of D. polymorpha mussels collected from four freshwater sites were investigated. Exposure of mussels to [(14)C]-E2 (7.5 ngl(-1), 13 days) revealed that the estrogen bioconcentrated 840+/-58 (males) and 580+/-77 (females) fold (mean+/-95% confidence limits) and was metabolised in tissues to a persistent lipophilic ester. Estrogenic activity, measured using a recombinant human estrogen receptor transcription screen (YES), was detected in tissue extracts of all mussels sampled from freshwater sites. At two reference sites the estrogenic activities of mussel tissues were <1ng E2 equivalents g(-1) wet weight tissue (ng EEQ g(-1) ww) which increased to 7.4-45.7ng EEQg(-1) ww for both free and esterified estrogens extracted from hydrolysed tissue extracts. In mussels collected from two contaminated river sites, estrogenic activity was 0.2-6.7ng EEQ g(-1) ww (free estrogens) and 25.6-316.2ng EEQ g(-1) ww for total estrogens. Fractionation of the tissue extracts revealed that E2 (as the ester) was the predominant estrogen detected in both sexes of D. polymorpha, however, the xenoestrogen nonylphenol (NP) was also detected in mussels sampled from contaminated rivers. The detection of endogenous esterified E2 and the potential for accumulation of exogenous E2 and NP in D. polymorpha tissues suggests that this bivalve could be susceptible to exposure to estrogenic contaminants in the aquatic environment.


Subject(s)
Dreissena/metabolism , Endocrine Disruptors/metabolism , Estradiol/pharmacokinetics , Estrogens/pharmacokinetics , Phenols/metabolism , Water Pollutants, Chemical/metabolism , Animals , Endocrine Disruptors/analysis , Endocrine Disruptors/toxicity , Environmental Monitoring , Estrogens/analysis , Estrogens/toxicity , Female , France , Geologic Sediments/analysis , Gonads/metabolism , Male , Phenols/analysis , Phenols/toxicity , Rivers , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Yeasts/drug effects , Yeasts/metabolism
14.
Aquat Toxicol ; 79(4): 376-83, 2006 Oct 12.
Article in English | MEDLINE | ID: mdl-16930737

ABSTRACT

To investigate the effect of estrogenic compounds on the marine mussel Mytilus edulis, an assay was developed to measure the expression of two vertebrate estrogen responsive genes-estrogen receptor (ER) and vitellogenin (VTG) genes. Expression was measured in M. edulis gonads following a 10-day exposure to 200 ng/l 17beta-estradiol (estradiol). The concentrations of esterified estradiol in mussel tissue increased 15-fold in a time-dependent manner-confirming uptake of the compound by the mussels, however there was no significant increase of free estradiol in mussel tissues during the exposure period. The ER and VTG mRNA levels in the gonads of both sexes were measured at days 1-3, 5, and 10 in control and exposed mussels. However, no significant change in the expression of either the ER or VTG genes was recorded at any of the sampled time points. The results suggest that either a regulatory mechanism exists in a mussel that is able to maintain constant levels of free estradiol by converting the excess estradiol into esterified products which may have reduced affinity for the estrogen receptor, or alternatively, that the ER and VTG genes are unresponsive to estrogens in these organisms. The significance of these findings in terms of the utility of ER and VTG as biomarkers of endocrine disruption in bivalve species is discussed.


Subject(s)
Estradiol/toxicity , Gene Expression/drug effects , Mytilus edulis/drug effects , Receptors, Estrogen/genetics , Vitellogenins/genetics , Water Pollutants, Chemical/toxicity , Amino Acid Sequence , Animals , DNA Primers/chemistry , Estradiol/analysis , Female , Gonads/chemistry , Gonads/drug effects , Male , Molecular Sequence Data , Mytilus edulis/chemistry , RNA, Messenger/analysis , Receptors, Estrogen/biosynthesis , Receptors, Estrogen/drug effects , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Sequence Alignment/veterinary , Vitellogenins/biosynthesis , Vitellogenins/drug effects , Water/analysis
15.
Environ Sci Technol ; 39(8): 2461-71, 2005 Apr 15.
Article in English | MEDLINE | ID: mdl-15884336

ABSTRACT

Most effluents from wastewater treatment works (WwTWs) contain estrogenic chemicals that include steroidal estrogens and xenoestrogens. We investigated the nature of mixtures of estrogenic contaminants taken up by two species of fish exposed to two WwTWs effluents. Sexually immature rainbow trout, Oncorhynchus mykiss, and sexually mature roach, Rutilus rutilus, were exposed to tap water, river water, or one of two estrogenic WwTWs effluents for up to 10 days, when the fish were sacrificed and tissues removed for chemical analysis. Estrogenic contaminants in the bile and gonads were hydrolyzed, concentrated by solid-phase extraction, and fractionated by RP-HPLC. Active fractions were detected and quantified using a yeast estrogen receptor transcription screen (YES assay) and the identities of estrogenic components in the fractions determined by GC-MS. Bile from rainbow trout exposed to either tap water or river water contained low amounts of 17beta-estradiol (E2) and estrone (E1) with a total estrogenic activity (mean+/-standard error) of 10+/-5 and 31+/-9 ng of E2 equivalents/mL (ng of E2eq/mL) for male and female fish, respectively. In effluent-exposed trout the total estrogen content of bile was considerably higher with the following composition and concentrations (ng of E2eq/mL) of individual estrogens: E2 (male, 591+/-125; female, 710+/-207), E1 (male, 338+/-75; female, 469+/-164), ethinylestradiol, EE2 (male, 32+/-2; female, 40+/-6), nonylphenol (NP) and short-chain NP polyethoxylates (male, 21+/-4; female, 22+/-3). An additional estrogenic compound, 17beta-dihydroequilenin (DHQ), was identified for the first time in effluent-exposed fish, and was present in trout bile at concentrations of (male) 40+/-9 and (female) 30+/-5 ng of E2 eq/mL. DHQ, E2, E1, and EE2, but not NP or NP polyethoxylates, were also detected in bile of effluent-exposed roach, and the concentrations of all these steroidal estrogens in ng of E2eq/mL were lower in male (E2, 62+/-2; E1, 35+/-11; EE2, 10+/-2; DHQ, 1+/-1) compared with female (E2, 740+/-197; E1, 197+/-37; EE2, 40+/-6; DHQ, 8+/-2) roach. The synthetic estrogen EE2 was also detected in the testes and ovaries of effluent-exposed roach. This study shows that a mixture of estrogenic contaminants present in WwTWs effluents bioconcentrate in fish tissues, resulting in the induction of vitellogenin, and are likely to contribute to feminizing effects in wild fish living in U.K. rivers. The composition of the mixture of estrogenic contaminants in the bile is species dependent and may determine the susceptibility of fish to the effects of exposure to estrogenic effluents.


Subject(s)
Bile/drug effects , Estrogens/analysis , Industrial Waste , Water Pollutants, Chemical/toxicity , Animals , Bile/chemistry , Dose-Response Relationship, Drug , Equilin/analogs & derivatives , Equilin/analysis , Equilin/metabolism , Estradiol/analysis , Estradiol/metabolism , Estradiol Congeners/analysis , Estradiol Congeners/metabolism , Estrogens/metabolism , Estrone/analysis , Estrone/metabolism , Ethinyl Estradiol/analysis , Ethinyl Estradiol/metabolism , Female , Fishes , Gonads/chemistry , Gonads/drug effects , Male , Phenols/analysis , Phenols/metabolism , Receptors, Estrogen/metabolism , Rivers , Water Supply
16.
Environ Sci Technol ; 39(8): 2599-607, 2005 Apr 15.
Article in English | MEDLINE | ID: mdl-15884355

ABSTRACT

Effluents from wastewater treatment works (WwTWs) contain estrogenic substances that induce feminizing effects in fish, including vitellogenin (VTG) synthesis and gonadal intersex. Fish vary in their responsiveness to estrogenic effluents, but the physiological basis for these differences are not known. In this study, uptake of estrogen from two WwTW effluents (measured in hydrolyzed bile) and estrogenic response (VTG induction) were compared in a salmonid (rainbow trout, Onchorhynchus mykiss) and a cyprinid fish (roach, Rutilus rutilus). Immature rainbow trout were more responsive than maturing roach to the estrogenic effluents. The more potent of the two estrogenic effluents (containing between 24.3 and 104.1 ng estradiol-17beta equivalents/L [E2eq/L]) resulted in a 700-fold and 240-fold induction of plasma VTG in male and female trout, respectively, but only a 4-fold induction in roach (and in males only). The less potent effluent (varying between 4.1 and 6.8 ng E2eq/L) induced VTG in the trout only, with a 4-fold and 18-fold induction in males and females, respectively. In fish exposed to tap water, the estrogenicity of the hydrolyzed bile was 0.03+/-0.01 ng E2eq/microL (for both sexes in trout), 0.18+/-0.04 ng E2eq/microL in male roach, and 0.88+/-0.15 ng E2eq/microL in female roach. The higher bile content of estrogen in control roach reflected their more advanced sexual status (and thus higher endogenous estrogen) compared with the immature female trout. In trout maintained in effluents, the bile content of estrogen was 100-fold and 30-fold higher than controls at WwTW A and B, respectively. Bioconcentration factors (BCFs) for estrogenic activity in bile were between 16 344 and 46 134 in trout and between 3543 and 60 192 in roach (no gender differences were apparent). There were strong correlations between VTG induction and the estrogenic activity of bile extracts for both trout and roach. The results confirm that estrogenic contaminants bioconcentrate to a high degree in fish bile and that the level (and nature) of this accumulation may accountfor responsiveness to the endocrine disruptive effects of estrogenic effluents. Immature fish were the more appropriate life stage for quantifying estrogen exposure and uptake in bile, as they contain little circulating endogenous oestrogen compared with sexual maturing fish. The nature of the estrogenic contaminants is detailed in an accompanying paper.


Subject(s)
Bile/drug effects , Environmental Exposure , Estrogens/pharmacology , Water Pollutants/toxicity , Animals , Bile/metabolism , Cyprinidae/metabolism , Female , Industrial Waste , Oncorhynchus mykiss/metabolism , Sexual Maturation , Vitellogenins/blood , Vitellogenins/metabolism
17.
J Chromatogr A ; 1066(1-2): 33-40, 2005 Feb 25.
Article in English | MEDLINE | ID: mdl-15794552

ABSTRACT

Effluents from wastewater treatment works (WwTWs) contain estrogenic contaminants that can cause feminised responses in fish. In order to assess the identity of estrogenic contaminants taken up by fish exposed to effluents, an analytical method was developed to detect estrogenic substances in fish bile, where many xenobiotics are excreted and concentrated. Estrogenic metabolites in bile were deconjugated using enzymatic hydrolysis and the estrogenic activity was determined using a yeast estrogen receptor transcription screen (YES). Hydrolysed samples were concentrated by solid-phase extraction (SPE) prior to fractionation by reversed-phase high-performance liquid chromatography (HPLC). Active HPLC fractions were detected by YES assay and analysed by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation. The method was validated using bile samples from immature female rainbow trout, which had been exposed to either tap water or an undiluted estrogenic effluent for 10 days. Hydrolysis of bile from effluent-exposed fish was complete within 16 h add most of the estrogenic activity in the bile was released by 3-glucuronidase rather than sulfatase or 3-glucosidase treatment. The estrogenic activity of hydrolysed bile from effluent-exposed fish ranged between 530 and 1440 ng E2eq/mL and was 17-48-fold greater than the activity of bile from reference fish exposed to tap water. The estrogenic activity of bile samples decreased with time in storage (at-70 degrees C by 7% per month). The recovery of estrogenic activity from SPE was 96 +/- 7% (mean +/- SD), from HPLC fractionation 87 +/- 7% and for the whole method 81 +/- 7% (n = 7). 17beta-Estradiol, estrone, 17alpha-ethinylestradiol, nonylphenol and short-chain nonylphenol polyethoxylates were all identified from GC-MS analysis of active HPLC fractions of bile from effluent-exposed trout, whereas only 17beta-estradiol was detected in bile from fish exposed to tap water. There were also several other minor estrogenic components, at present unidentified, in bile of effluent-exposed fish. The work shows that fractionation of fish bile is a useful approach to identifying mixtures of estrogenic contaminants taken up by fish from WwTW effluents and has the potential for application in the detection of other endocrine disrupting chemicals in fish tissues.


Subject(s)
Bile/chemistry , Estrogens/analysis , Fishes , Water Pollutants/analysis , Animals , Biological Assay , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Humans , Hydrolysis , Receptors, Estrogen/genetics , Recombinant Proteins , Saccharomyces cerevisiae
18.
Psychiatr Rehabil J ; 25(1): 3-11, 2001.
Article in English | MEDLINE | ID: mdl-11529450

ABSTRACT

This study examined the predictors of psychosocial outcomes (daily functioning and management of illness) for people with mood disorders. After controlling for demographic, severity of illness, and social support predictor variables, the study evaluated whether participation in self-help groups would predict improved psychosocial outcomes. Post-hospitalization data were examined for 144 mood disorder patients using hierarchic multiple regression. More education predicted improved daily functioning; self-help involvement and education predicted management of illness. The implications of these findings for providing recovery-oriented rehabilitation services are discussed.


Subject(s)
Mood Disorders/therapy , Self-Help Groups , Adolescent , Adult , Female , Humans , Male , Mood Disorders/diagnosis , Prospective Studies , Random Allocation , Severity of Illness Index , Social Support , Surveys and Questionnaires
19.
Subst Use Misuse ; 36(5): 609-38, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11419490

ABSTRACT

Within-family differences that mediate the relationship between family history for alcoholism and alcohol consumption were investigated. Twenty adult children of alcoholics (ACOAs) and 20 children of social drinking parents (non-ACOAs) were interviewed in 1991 (mean age 24.2 years). Participants described family functioning while growing up and indices of their alcohol consumption. Family history for alcoholism had a direct association with two aspects of drinking. ACOAs reported more lifetime drinks and tended to report drinking more frequently during high school, as compared to non-ACOAs. ACOAs also reported more parental unpredictability, which in turn was associated with the above drinking indices. Finally, family history for alcoholism had an indirect association with drinking, as unpredictability mediated this relationship. Research and prevention implications are discussed.


Subject(s)
Alcohol Drinking/psychology , Alcoholism/psychology , Child of Impaired Parents/psychology , Adolescent , Adolescent Behavior/psychology , Adult , Family Characteristics , Female , Humans , Male , Parent-Child Relations , Parenting/psychology , Pilot Projects
20.
Mar Environ Res ; 51(1): 75-89, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11125704

ABSTRACT

Branched chain alkylphenols are weak oestrogen mimics which are present in the aquatic environment and have been implicated in the feminisation of fish. This study reports the biotransformation, bioconcentration and tissue distribution of the xenoestrogen 4-tert-octylphenol (t-OP) in juvenile rainbow trout. Fish were exposed for 10 days to a concentration of 4 micrograms/l of [14C] t-OP in a flow-through system and were sampled after 1, 4, 7 and 10 days of exposure. t-OP residues were extracted from all tissues and analysed by radio-high-performance liquid chromatography. After 1 day of exposure radioactive residues were detected in all tissues and reached steady state conditions in the whole fish after 4 days of exposure. The concentration of t-OP residues were highest in bile, followed by faeces, pyloric caeca, liver and intestine. In these tissues the majority of alkylphenol was in the form of two metabolites which were identified by gas chromatography-mass spectroscopy as the glucuronide conjugates of t-OP and t-octylcatechol. t-OP accumulated as the parent compound in fat with a bioconcentration factor (BCF) of 1190, and in brain, muscle, skin, bone, gills, and eye with BCFs of between 100 and 260. This study suggests that exposure to water-borne alkylphenols results in rapid conjugation and elimination of the chemical via the liver/bile route, but that high amounts of the parent xenoestrogen can accumulate in a variety of other fish tissues.


Subject(s)
Oncorhynchus mykiss/metabolism , Phenols/pharmacokinetics , Surface-Active Agents/pharmacokinetics , Animals , Biotransformation , Chromatography, High Pressure Liquid/veterinary , Gas Chromatography-Mass Spectrometry/veterinary , Tissue Distribution
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