RESUMO
Atmospheric mercury (Hg) emissions and subsequent transport and deposition are major concerns within protected lands, including national parks, where Hg can bioaccumulate to levels detrimental to human and wildlife health. Despite this risk to biological resources, there is limited understanding of the relative importance of different Hg sources and delivery pathways within the protected regions. Here, we used Hg stable isotope measurements within a single aquatic bioindicator, dragonfly larvae, to determine if these tracers can resolve spatial patterns in Hg sources, delivery mechanisms, and aquatic cycling at a national scale. Mercury isotope values in dragonfly tissues varied among habitat types (e.g., lentic, lotic, and wetland) and geographic location. Photochemical-derived isotope fractionation was habitat-dependent and influenced by factors that impact light penetration directly or indirectly, including dissolved organic matter, canopy cover, and total phosphorus. Strong patterns for Δ200Hg emerged in the western United States, highlighting the relative importance of wet deposition sources in arid regions in contrast to dry deposition delivery in forested regions. This work demonstrates the efficacy of dragonfly larvae as biosentinels for Hg isotope studies due to their ubiquity across freshwater ecosystems and ability to track variation in Hg sources and processing attributed to small-scale habitat and large-scale regional patterns.
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Quantifying how contaminants change across life cycles of species that undergo metamorphosis is critical to assessing organismal risk, particularly for consumers. Pond-breeding amphibians can dominate aquatic animal biomass as larvae and are terrestrial prey as juveniles and adults. Thus, amphibians can be vectors of mercury exposure in both aquatic and terrestrial food webs. However, it is still unclear how mercury concentrations are affected by exogenous (e.g., habitat or diet) vs endogenous factors (e.g., catabolism during hibernation) as amphibians undergo large diet shifts and periods of fasting during ontogeny. We measured total mercury (THg), methylmercury (MeHg), and isotopic compositions (δ 13C, δ15N) in boreal chorus frogs (Pseudacris maculata) across five life stages in two Colorado (USA) metapopulations. We found large differences in concentrations and percent MeHg (of THg) among life stages. Frog MeHg concentrations peaked during metamorphosis and hibernation coinciding with the most energetically demanding life cycle stages. Indeed, life history transitions involving periods of fasting coupled with high metabolic demands led to large increases in mercury concentrations. The endogenous processes of metamorphosis and hibernation resulted in MeHg bioamplification, thus decoupling it from the light isotopic proxies of diet and trophic position. These step changes are not often considered in conventional expectations of how MeHg concentrations within organisms are assessed.
Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Animais , Lagoas , Mercúrio/análise , Compostos de Metilmercúrio/metabolismo , Ecossistema , Cadeia Alimentar , Anfíbios/metabolismo , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Peixes/metabolismoRESUMO
OBJECTIVE: To examine the screening-treatment-mortality pathway among women with invasive breast cancer in 2006-2014 using linked data. METHODS: BreastScreen histories of South Australian women diagnosed with breast cancer (n = 8453) were investigated. Treatments recorded within 12 months from diagnosis were obtained from linked registry and administrative data. Associations of screening history with treatment were investigated using logistic regression and with cancer mortality outcomes using competing risk analyses, adjusting for socio-demographic, cancer and comorbidity characteristics. RESULTS AND CONCLUSION: For screening ages of 50-69 years, 70% had participated in BreastScreen SA ≤ 5 years and 53% ≤ 2 years of diagnosis. Five-year disease-specific survival post-diagnosis was 90%. Compared with those not screened ≤5 years, women screened ≤2 years had higher odds, adjusted for socio-demographic, cancer and comorbidity characteristics, and diagnostic period, of breast-conserving surgery (aOR 2.5, 95% CI 1.9-3.2) and radiotherapy (aOR 1.2, 95% CI 1.1-1.3). These women had a lower unadjusted risk of post-diagnostic cancer mortality (SHR 0.33, 95% CI 0.27-0.41), partly mediated by stage (aSHR 0.65, 95% CI 0.51-0.81), and less breast surgery (aSHR 0.78, 95% CI 0.62-0.99). Screening ≤2 years and conserving surgery appeared to have a greater than additive association with lower post-diagnostic mortality (interaction term SHR 0.42, 95% CI 0.23-0.78). The screening-treatment-mortality pathway was investigated using linked data.
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Neoplasias da Mama , Idoso , Austrália , Neoplasias da Mama/terapia , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Web SemânticaRESUMO
OBJECTIVE: We investigated treatment and survival by clinical and sociodemographic characteristics for service evaluation using linked data. METHOD: Data on invasive female breast cancers (n = 13,494) from the South Australian Cancer Registry (2000-2014 diagnoses) were linked to hospital inpatient, radiotherapy and universal health insurance data. Treatments ≤12 months from diagnosis and survival were analysed, using adjusted odds ratios (aORs) from logistic regression, and adjusted sub-hazard ratios (aSHRs) from competing risk regression. RESULTS AND CONCLUSION: Five-year disease-specific survival increased to 91% for 2010-2014. Most women had breast surgery (90%), systemic therapy (72%) and radiotherapy (60%). Less treatment applied for ages 80+ vs <50 years (aOR 0.10, 95% CI 0.05-0.20) and TNM stage IV vs stage I (aOR 0.13, 95% CI 0.08-0.22). Surgical treatment increased during the study period and strongly predicted higher survival. Compared with no surgery, aSHRs were 0.31 (95% CI 0.26-0.36) for women having breast-conserving surgery, 0.49 (95% CI 0.41-0.57) for mastectomy and 0.42 (95% CI 0.33-0.52) when both surgery types were received. Patients aged 80+ years had lower survival and less treatment. More trial evidence is needed to optimise trade-offs between benefits and harms in these older women. Survival differences were not found by residential remoteness and were marginal by socioeconomic status.
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Neoplasias da Mama , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Neoplasias da Mama/patologia , Feminino , Humanos , Mastectomia , Mastectomia Segmentar , Estadiamento de Neoplasias , Web Semântica , Austrália do Sul/epidemiologiaRESUMO
Mercury (Hg) is a pervasive environmental pollutant and contaminant of concern for both people and wildlife that has been a focus of environmental remediation efforts for decades. A growing body of literature has motivated calls for revising Hg consumption advisories to co-consider selenium (Se) levels in seafood and implies that remediating aquatic ecosystems with ecosystem-scale Se additions could be a robust solution to Hg contamination. Provided that elevated Se concentrations are also known toxicological threats to aquatic animals, we performed a literature search to evaluate the strength of evidence supporting three assertions underpinning the ameliorating benefits of Se: (1) dietary Se reduces MeHg toxicity in consumers; (2) environmental Se reduces Hg bioaccumulation and biomagnification in aquatic food webs; and (3) Se inhibits Hg bioavailability to, and/or methylmercury production by, microbial communities. Limited or ambiguous support for each criterion indicates that many scientific uncertainties and gaps remain regarding Se mediation of Hg behavior and toxicity in abiotic and biotic compartments. Significantly more information is needed to provide a strong scientific basis for modifying current fish consumption advisories on the basis of Se:Hg ratios or for applying Se amendments to remediate Hg-contaminated ecosystems.
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Mercúrio , Compostos de Metilmercúrio , Selênio , Poluentes Químicos da Água , Animais , Ecossistema , Monitoramento Ambiental , Peixes , Humanos , Mercúrio/análise , Selênio/análise , Poluentes Químicos da Água/análiseRESUMO
Selenium is highly elevated in Appalachian streams and stream organisms that receive alkaline mine drainage from mountaintop removal coal mining compared to unimpacted streams in the region. Adult aquatic insects can be important vectors of waterborne contaminants to riparian food webs, yet pathways of Se transport and exposure of riparian organisms are poorly characterized. We investigated Se concentrations in stream and riparian organisms to determine whether mining extent increased Se uptake in stream biofilms and insects and if these insects were effective Se biovectors to riparian spiders. Biofilm Se concentration increased (p = 0.006) with mining extent, reaching a maximum value of 16.5 µg/g of dw. Insect and spider Se increased with biofilm Se (p = 0.004, p = 0.003), reaching 95 and 26 µg/g of dw, respectively, in mining-impacted streams. Adult insect biomass was not related to mining extent or Se concentrations in biofilm. Even though Se concentrations in aquatic insects were significantly and positively related to mining extent, aquatic insect Se flux was not associated with mining extent because the mass of emerging insects did not change appreciably over the mining gradient. Insect and spider Se concentrations were among the highest reported in the literature, regularly exceeding the bird Se dietary risk threshold of 5 µg/g of dw. Risks of Se exposure and toxicity related to mining are thus not constrained to aquatic systems but extend to terrestrial habitats and food webs.
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Minas de Carvão , Aranhas , Animais , Região dos Apalaches , Cadeia Alimentar , Insetos , RiosRESUMO
Little is known about the underlying mechanisms governing the bioaccumulation of uranium (U) in aquatic insects. We experimentally parameterized conditional rate constants for aqueous U uptake, dietary U uptake, and U elimination for the aquatic baetid mayfly Neocloeon triangulifer. Results showed that this species accumulates U from both the surrounding water and diet, with waterborne uptake prevailing. Elevated dietary U concentrations decreased feeding rates, presumably by altering food palatability or impairing the mayfly's digestive processes, or both. Nearly 90% of the accumulated U was eliminated within 24 h after the waterborne exposure ceased, reflecting the desorption of weakly bound U from the insect's integument. To examine whether the experimentally derived rate constants for N. triangulifer could be generalized to baetid mayflies, mayfly U concentrations were predicted using the water chemistry and U measured in periphyton from springs in Grand Canyon (United States) and were compared to U concentrations in spring-dwelling mayflies. Predicted and observed mayfly U concentrations were in good agreement. Under the modeled site-specific conditions, waterborne U uptake accounted for 52-93% of the bioaccumulated U. U accumulation was limited in these wild populations due to a combination of factors including low concentrations of bioavailable dissolved U species, slow U uptake rates from food, and fast U elimination.
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Ephemeroptera , Perifíton , Urânio , Poluentes Químicos da Água , Animais , Bioacumulação , InsetosRESUMO
Complement is a key component of innate immunity in health and a powerful driver of inflammation and tissue injury in disease. The biological and pathological effects of complement activation are mediated by activation products. These come in two flavors: (i) proteolytic fragments of complement proteins (C3, C4, C5) generated during activation that bind specific receptors on target cells to mediate effects; (ii) the multimolecular membrane attack complex generated from the five terminal complement proteins that directly binds to and penetrates target cell membranes. Several recent publications have described structural insights that have changed perceptions of the nature of this membrane attack complex. This review will describe these recent advances in understanding of the structure of the membrane attack complex and its by-product the fluid-phase terminal complement complex and relate these new structural insights to functional consequences and cell responses to complement membrane attack.
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Membrana Celular/metabolismo , Ativação do Complemento , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Proteínas do Sistema Complemento/imunologia , Animais , Humanos , Imunidade Inata , Conformação Proteica , Relação Estrutura-AtividadeRESUMO
C5 plays a major role in complement activation; C5 convertase cleaves C5 into the pro-inflammatory C5a, and C5b, the nidus for the formation of the lytic membrane attack complex. C5 is a major target for anti-complement drugs, necessitating better methods for the study of C5 function. Purification of C5 is complicated; classical methods involve precipitation or pH shifts that result in functional loss and low yield. We here present a method for C5 purification using a novel anti-C5 monoclonal antibody (mAb); RO7112689 (C5i mAb, SKY59), pH-switch engineered to induce antibody-antigen dissociation in the acidic endosome (~ pH 5·5). RO7112689 was bound on an affinity column; applied serum was completely depleted of C5. Elution at pH 5 produced fully active C5 at 98% yield. The mAb also bound C5b in the C5b6 complex, preventing C5b6 binding to target membranes and enabling purification of C5b6 from activated serum. RO7112689 inhibited C5 in mouse serum and efficiently purified mouse C5. Used as capture, RO7112689 produced sensitive and specific assays for human and mouse C5. This novel antibody enables efficient production of intact, fully active, pure human and mouse C5, and quantification of C5 in these species. The demonstration that RO7112689 binds C5b6 adds an additional mechanism of membrane attack complex inhibition by this mAb.
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Anticorpos Monoclonais Murinos/química , Complemento C5 , Proteínas do Sistema Complemento , Animais , Cromatografia de Afinidade/métodos , Complemento C5/química , Complemento C5/imunologia , Complemento C5/isolamento & purificação , Proteínas do Sistema Complemento/química , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/isolamento & purificação , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Especificidade da EspécieRESUMO
BACKGROUND: Detection of breast cancers by mammographic screening confers a survival advantage of 20-50% compared to symptomatic presentations. The improved prognosis is only partly explained by stage migration. The distribution of the molecular subtypes of screen-detected breast cancer (SDBC) or their HER2 status has not been studied extensively. We wished to address these issues through the study of a large series of SDBC, with other presentations serving as controls. DESIGN: Deidentified cases of female invasive cancer, diagnosed in Australia and New Zealand during 2005-2015, were retrieved from the BreastSurgANZ Quality Audit (BQA). Method of detection and selected patient, tumour and treatment data were assessed. Immunohistochemical surrogates for molecular subtypes were defined as Luminal A (ER+ and/or PR+, HER2-), Luminal B (ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR- and HER2+) and basal-like (triple negative). Results were compared with the findings of controls and previous studies. RESULT: 100983 invasive cancers were diagnosed, including 32493 (32.7%) SDBC and 66907 (67.3%) with other presentations. The biomarker profile for SDBC versus other presentations in the same population was ER 89.3 versus 80.3%, PR 78.8 versus 69.8% and for HER2 11 versus 15.6%. The distribution of molecular subtypes was Luminal A 81.9 versus 70.74%, Luminal B 7.39 versus 9.52%, HER2-enriched 3.63 versus 6.06% and Basal-like 7.08 versus 13.68%. These differences were significant (p < 0.0001). CONCLUSION: Molecular profiles of SDBC are significantly different from those of symptomatic cancers, with over-representation of the Luminal A and proportionately lower rates of all other subtypes. We have shown, for the first time, significantly lower rates of HER2 positivity in SDBC. These differences may contribute to the better survival of SDBC and have implications for prognostication, targeted therapy decisions and for laboratory quality assurance programs in setting target ranges for proportions of ER-positive and HER2 results in heavily screened populations.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer , Adulto , Idoso , Austrália/epidemiologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genéticaRESUMO
In the Colorado Front Range (USA), disturbance history dictates stream planform. Undisturbed, old-growth streams have multiple channels and large amounts of wood and depositional habitat. Disturbed streams (wildfires and logging < 200 years ago) are single-channeled with mostly erosional habitat. We tested how these opposing stream states influenced organic matter, benthic macroinvertebrate secondary production, emerging aquatic insect flux, and riparian spider biomass. Organic matter and macroinvertebrate production did not differ among sites per unit area (m-2), but values were 2 ×-21 × higher in undisturbed reaches per unit of stream valley (m-1 valley) because total stream area was higher in undisturbed reaches. Insect emergence was similar among streams at the per unit area and per unit of stream valley. However, rescaling insect emergence to per meter of stream bank showed that the emerging insect biomass reaching the stream bank was lower in undisturbed sites because multi-channel reaches had 3 × more stream bank than single-channel reaches. Riparian spider biomass followed the same pattern as emerging aquatic insects, and we attribute this to bottom-up limitation caused by the multi-channeled undisturbed sites diluting prey quantity (emerging insects) reaching the stream bank (riparian spider habitat). These results show that historic landscape disturbances continue to influence stream and riparian communities in the Colorado Front Range. However, these legacy effects are only weakly influencing habitat-specific function and instead are primarily influencing stream-riparian community productivity by dictating both stream planform (total stream area, total stream bank length) and the proportional distribution of specific habitat types (pools vs riffles).
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Rios , Aranhas , Animais , Colorado , Ecossistema , Dinâmica PopulacionalRESUMO
Insect metamorphosis often results in substantial chemical changes that can alter contaminant concentrations and fractionate isotopes. We exposed larval mayflies (Baetis tricaudatus) and their food (periphyton) to an aqueous zinc gradient (3-340 µg Zn/l) and measured zinc concentrations at different stages of metamorphosis: larval, subimago, and imago. We also measured changes in stable isotopes (δ15N and δ13C) in unexposed mayflies. Larval zinc concentrations were positively related to aqueous zinc, increasing 9-fold across the exposure gradient. Adult zinc concentrations were also positively related to aqueous zinc, but were 7-fold lower than larvae. This relationship varied according to adult substage and sex. Tissue concentrations in female imagoes were not related to exposure concentrations, but the converse was true for all other stage-by-sex combinations. Metamorphosis also increased δ15N by â¼0.8, but not δ13C. Thus, the main effects of metamorphosis on insect chemistry were large declines in zinc concentrations coupled with increased δ15N signatures. For zinc, this change was largely consistent across the aqueous exposure gradient. However, differences among sexes and stages suggest that caution is warranted when using nitrogen isotopes or metal concentrations measured in one insect stage (e.g., larvae) to assess risk to wildlife that feed on subsequent life stages (e.g., adults).
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Ephemeroptera , Metamorfose Biológica/efeitos dos fármacos , Animais , Larva/efeitos dos fármacos , Metais/farmacologia , Zinco/farmacologiaRESUMO
BACKGROUND AND PURPOSE: There is limited evidence for remote stroke thrombolysis using telephone consultation and teleradiology. Results from a UK network using this treatment model are presented. METHODS: Retrospective study of consecutive patients thrombolysed in 5 hospitals, with well organized stroke services, between 2012 and 2013. Remote thrombolysis was compared with thrombolysis delivered in person for symptomatic intracerebral hemorrhage, death within 7 days, and 90-day modified Rankin scores. RESULTS: Of 586 patients, 220 (37.5%) were thrombolysed remotely. The 2 groups were well matched (median age 77 years, NIHSS 12). Remote thrombolysis increased treatment time by 22 minutes. Outcomes were no different in the 2 groups (remote versus standard): symptomatic intracerebral hemorrhage (3.6% versus 4.6%), death within 7 days (6.4% versus 7.1%), modified Rankin score <2 (46.0% versus 46.1%), and modified Rankin score 6 (15% versus 17.5%) at 90 days. CONCLUSION: Telephone advice and teleradiology, within an organized system of care, can be an effective method of delivery of intravenous thrombolysis.
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Isquemia Encefálica/tratamento farmacológico , Cardiologia/métodos , Infusões Intravenosas/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Telemedicina/métodos , Terapia Trombolítica/métodos , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Telefone , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento , Reino UnidoRESUMO
Opposing hypotheses posit that increasing primary productivity should result in either greater or lesser contaminant accumulation in stream food webs. We conducted an experiment to evaluate primary productivity effects on MeHg accumulation in stream consumers. We varied light for 16 artificial streams creating a productivity gradient (oxygen production =0.048-0.71 mg O2 L(-1) d(-1)) among streams. Two-level food webs were established consisting of phytoplankton/filter feeding clam, periphyton/grazing snail, and leaves/shredding amphipod (Hyalella azteca). Phytoplankton and periphyton biomass, along with MeHg removal from the water column, increased significantly with productivity, but MeHg concentrations in these primary producers declined. Methylmercury concentrations in clams and snails also declined with productivity, and consumer concentrations were strongly correlated with MeHg concentrations in primary producers. Heterotroph biomass on leaves, MeHg in leaves, and MeHg in Hyalella were unrelated to stream productivity. Our results support the hypothesis that contaminant bioaccumulation declines with stream primary production via the mechanism of bloom dilution (MeHg burden per cell decreases in algal blooms), extending patterns of contaminant accumulation documented in lakes to lotic systems.
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Cadeia Alimentar , Compostos de Metilmercúrio/análise , Rios , Poluentes Químicos da Água/análise , Anfípodes/efeitos dos fármacos , Animais , Biomassa , Bivalves/efeitos dos fármacos , Bivalves/metabolismo , Eutrofização , Processos Heterotróficos , Compostos de Metilmercúrio/farmacocinética , Oxigênio/metabolismo , Fitoplâncton/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Caramujos/efeitos dos fármacos , Caramujos/metabolismo , Poluentes Químicos da Água/farmacocinéticaRESUMO
The effects of aquatic contaminants are propagated across ecosystem boundaries by aquatic insects that export resources and contaminants to terrestrial food webs; however, the mechanisms driving these effects are poorly understood. We examined how emergence, contaminant concentration, and total contaminant flux by adult aquatic insects changed over a gradient of bioavailable metals in streams and how these changes affected riparian web-building spiders. Insect emergence decreased 97% over the metal gradient, whereas metal concentrations in adult insects changed relatively little. As a result, total metal exported by insects (flux) was lowest at the most contaminated streams, declining 96% among sites. Spiders were affected by the decrease in prey biomass, but not by metal exposure or metal flux to land in aquatic prey. Aquatic insects are increasingly thought to increase exposure of terrestrial consumers to aquatic contaminants, but stream metals reduce contaminant flux to riparian consumers by strongly impacting the resource linkage. Our results demonstrate the importance of understanding the contaminant-specific effects of aquatic pollutants on adult insect emergence and contaminant accumulation in adults to predict impacts on terrestrial food webs.
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Insetos/efeitos dos fármacos , Metais/toxicidade , Rios/química , Aranhas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Cadeia Alimentar , Insetos/fisiologia , Metais/química , Dinâmica Populacional , Aranhas/fisiologia , Poluentes Químicos da Água/química , Poluição Química da ÁguaRESUMO
Insects are integral to most freshwater and terrestrial food webs, but due to their accumulation of environmental pollutants they are also contaminant vectors that threaten reproduction, development, and survival of consumers. Metamorphosis from larvae to adult can cause large chemical changes in insects, altering contaminant concentrations and fractionation of chemical tracers used to establish contaminant biomagnification in food webs, but no framework exists for predicting and managing these effects. We analyzed data from 39 studies of 68 analytes (stable isotopes and contaminants), and found that metamorphosis effects varied greatly. δ(15)N, widely used to estimate relative trophic position in biomagnification studies, was enriched by ⼠1 during metamorphosis, while δ(13)C used to estimate diet, was similar in larvae and adults. Metals and polycyclic aromatic hydrocarbons (PAHs) were predominantly lost during metamorphosis leading to ⼠2 to 125-fold higher larval concentrations and higher exposure risks for predators of larvae compared to predators of adults. In contrast, manufactured organic contaminants (such as polychlorinated biphenyls) were retained and concentrated in adults, causing up to ⼠3-fold higher adult concentrations and higher exposure risks to predators of adult insects. Both food web studies and contaminant management and mitigation strategies need to consider how metamorphosis affects the movement of materials between habitats and ecosystems, with special regard for aquatic-terrestrial linkages.
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Poluentes Ambientais/farmacocinética , Cadeia Alimentar , Insetos/química , Metamorfose Biológica/fisiologia , Animais , Isótopos de Carbono/análise , Isótopos de Carbono/farmacocinética , Poluentes Ambientais/análise , Insetos/fisiologia , Marcação por Isótopo , Metais Pesados/análise , Metais Pesados/farmacocinética , Isótopos de Nitrogênio/análise , Isótopos de Nitrogênio/farmacocinética , Bifenilos Policlorados/análise , Bifenilos Policlorados/farmacocinética , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Análise de RegressãoRESUMO
INTRODUCTION: The risk of breast cancer recurrence has been linked to tumour size, grade, oestrogen (ER) receptor status, and degree of lymph node (LN) involvement. However, the role of these variables in predicting time to relapse is not well defined. This study was designed to identify patient and primary tumour characteristics that predict risk periods for breast cancer recurrence within our institution, to enable more tailored surveillance strategies. METHODS: We retrospectively studied a cohort of 473 patients who presented to The Queen Elizabeth Hospital, Adelaide, Australia, with recurrent breast cancer between 1968 and 2008. Patient and primary tumour characteristics were collected, including age, menopausal status, tumour grade, size, ER and progesterone receptor (PR) status, and LN involvement and modeled against time to relapse using Kaplan-Meier survival curves. RESULTS: High tumour grade, size ≥ 20 mm, ER negativity, and PR negativity were shown on univariate analysis to correlate significantly with earlier recurrence (P < 0.0001, P = 0.0012, P = 0.0006, and P = 0.006). Multivariate analysis identified tumour grade and size as significant predictors of timing of relapse after adjustment for other variables. LN involvement, menopausal status, and age did not significantly correlate with earlier recurrence. CONCLUSIONS: High tumour grade and larger size were shown to independently predict earlier breast cancer relapse. While LN involvement increases absolute recurrence risk, our study proposes that it does not influence timing of relapse. Use of these predictors will enable key risk periods for onset of relapse to be characterised according to tumour profile with more appropriate discharge to primary care providers for ongoing surveillance.
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Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Receptores de Estrogênio/análise , Estudos Retrospectivos , Fatores de Tempo , Carga Tumoral , Adulto JovemRESUMO
OBJECTIVE: To investigate patient, cancer and treatment factors associated with the residence of female breast cancer patients in lower socioeconomic areas of Australia to better understand factors that may contribute to their poorer cancer outcomes. METHODS: Bivariable and multivariable analyses were performed using the Breast Quality Audit database of Breast Surgeons of Australia and New Zealand. RESULTS Multivariable regression indicated that patients from lower socioeconomic areas are more likely to live in more remote areas and to be treated at regional than major city centres. Although they appeared equally likely to be referred to surgeons from BreastScreen services as patients from higher socioeconomic areas, they were less likely to be referred as asymptomatic cases from other sources. In general, their cancer and treatment characteristics did not differ from those of women from higher socioeconomic areas, but ovarian ablation therapy was less common for these patients and bilateral synchronous lesions tended to be less frequent than for women from higher socioeconomic areas. CONCLUSIONS: The results indicate that patients from lower socioeconomic areas are more likely to live in more remote districts and have their treatment in regional rather than major treatment centres. Their cancer and treatment characteristics appear to be similar to those of women from higher socioeconomic areas, although they are less likely to have ovarian ablation or to be referred as asymptomatic patients from sources other than BreastScreen. What is known about this topic? It is already known from Australian data that breast cancer outcomes are not as favourable for women from areas of socioeconomic disadvantage. The reasons for the poorer outcomes have not been understood. Studies in other countries have also found poorer outcomes in women from lower socioeconomic areas, and in some instances, have attributed this finding to more advanced stages of cancers at diagnosis and more limited treatment. The reasons are likely to vary with the country and health system characteristics. What does this paper add? The present study found that in Australia, women from lower socioeconomic areas do not have more advanced cancers at diagnosis, nor, in general, other cancer features that would predispose them to poorer outcomes. The standout differences were that they tended more to live in areas that were more remote from specialist metropolitan centres and were more likely to be treated in regional settings where prior research has indicated poorer outcomes. The reasons for these poorer outcomes are not known but may include lower levels of surgical specialisation, less access to specialised adjunctive services, and less involvement with multidisciplinary teams. Women from lower socioeconomic areas also appeared more likely to attend lower case load surgeons. Little difference was evident in the type of clinical care received, although women from lower socioeconomic areas were less likely to be asymptomatic referrals from other clinical settings (excluding BreastScreen). What are the implications for practitioners? Results suggest that poorer outcomes in women from lower socioeconomic areas in Australia may have less to do with the characteristics of their breast cancers or treatment modalities and more to do with health system features, such as access to specialist centres. This study highlights the importance of demographic and health system features as potentially key factors in service outcomes. Health system research should be strengthened in Australia to augment biomedical and clinical research, with a view to best meeting service needs of all sectors of the population.
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Neoplasias da Mama/terapia , Acessibilidade aos Serviços de Saúde/economia , Disparidades nos Níveis de Saúde , Avaliação de Resultados em Cuidados de Saúde/economia , Classe Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Austrália/epidemiologia , Neoplasias da Mama/economia , Neoplasias da Mama/etnologia , Feminino , Humanos , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: The purpose of this study was to examine the likelihood of driving after using cannabis, and of being a passenger with someone who is driving after using cannabis, in rural areas and non-rural areas before and after legalization. METHODS: A multi-wave analysis of Canada's National Cannabis Survey was conducted using logistic regression with interactions to predict the prevalence of driving after using cannabis, and of being a passenger with someone who is driving after using cannabis, in relation to place of residence (rural or non-rural) and in the weeks and months before and after legalization. Three time points were compared: pre-legalization, two months following legalization and 1 year after legalization. RESULTS: At the national level, there are no significant differences between the predicted estimates of driving after using cannabis for those who live in rural and non-rural areas. However, when examining the impact of legalization, we found a significant increase in driving after using cannabis among rural residents directly following legalization. Furthermore, it was observed that this increase in driving after using cannabis returns to pre-legalization rates one year after legalization. By contrast, in the weeks and months following legalization, driving after using cannabis decreased among those living in non-rural areas, and slowly increased soon thereafter. No significant differences were observed, in either time period or group, in the prevalence of being a passenger with someone who is driving after using cannabis. CONCLUSIONS: The finding of significantly higher risk of driving after use of cannabis soon after legalization in rural areas suggests a need for more attention to address immediate concerns for public safety. The increased potential for traffic injuries and deaths in other jurisdictions contemplating legalization supports the call for more and better targeted prevention efforts in rural communities that have far too often been overlooked and under-served.
Assuntos
Cannabis , Humanos , Prevalência , População Rural , Acidentes de Trânsito , Canadá/epidemiologiaRESUMO
Quantifying the effects of environmental stressors on natural resources is problematic because of complex interactions among environmental factors that influence endpoints of interest. This complexity, coupled with data limitations, propagates uncertainty that can make it difficult to causally associate specific environmental stressors with injury endpoints. The Natural Resource Damage Assessment and Restoration (NRDAR) regulations under the Comprehensive Environmental Response, Compensation, and Liability Act and Oil Pollution Act aim to restore natural resources injured by oil spills and hazardous substances released into the environment; exploration of alternative statistical methods to evaluate effects could help address NRDAR legal claims. Bayesian networks (BNs) are statistical tools that can be used to estimate the influence and interrelatedness of abiotic and biotic environmental variables on environmental endpoints of interest. We investigated the application of a BN for injury assessment using a hypothetical case study by simulating data of acid mine drainage (AMD) affecting a fictional stream-dwelling bird species. We compared the BN-generated probability estimates for injury with a more traditional approach using toxicity thresholds for water and sediment chemistry. Bayesian networks offered several distinct advantages over traditional approaches, including formalizing the use of expert knowledge, probabilistic estimates of injury using intermediate direct and indirect effects, and the incorporation of a more nuanced and ecologically relevant representation of effects. Given the potential that BNs have for natural resource injury assessment, more research and field-based application are needed to determine their efficacy in NRDAR. We expect the resulting methods will be of interest to many US federal, state, and tribal programs devoted to the evaluation, mitigation, remediation, and/or restoration of natural resources injured by releases or spills of contaminants. Integr Environ Assess Manag 2024;20:562-573. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).