RESUMO
OBJECTIVES: Homelessness is both a significant determinant and consequence of health and social inequalities. To better meet healthcare needs, dedicated mental health and general nurses were implemented to deliver outreach healthcare to people experiencing homelessness in one United Kingdom (UK) county. During COVID-19, the UK Government also instructed local authorities to accommodate individuals sleeping rough and have a national target to end rough sleeping. This qualitative study explored experiences of this nurse-let outreach service and housing journeys during and beyond COVID-19 among people experiencing homelessness. STUDY DESIGN: Face-to-face, narrative storytelling interviews were conducted via opportunistic sampling in community settings. Individuals with recent or current experiences of homelessness were eligible. METHODS: Participants were informed about the study via known professionals and introduced to the researcher. Eighteen narrative interviews were conducted, transcribed, and analysed using reflective thematic analysis. RESULTS: Individuals described complex journeys in becoming and being homeless. The nurse-led outreach service provided integral support, with reported benefits to person-centred and accessible care and improved outcomes in health and well-being. After being housed, individuals valued housing necessities and described new responsibilities. However, some participants did not accept or stay in housing provisions where they perceived risks. CONCLUSIONS: Interviewed participants perceived that the dedicated nurse-led outreach service improved their access to care and health outcomes. In the absence of dedicated provisions, mainstream healthcare should ensure flexible processes and collaborative professional working. Local authorities must also be afforded increased resources for housing, as well as integrated support, to reduce social and health inequalities.
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COVID-19 , Pessoas Mal Alojadas , Humanos , Habitação , Atenção à Saúde , Saúde Mental , COVID-19/epidemiologiaRESUMO
BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.
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Ileostomia , Íleus , Humanos , Ileostomia/efeitos adversos , Flatulência/complicações , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Íleus/etiologiaRESUMO
Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided.
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Rotas de Resultados Adversos , Medição de Risco/métodos , Testes de Toxicidade/métodos , Animais , Carcinógenos/química , Carcinógenos/toxicidade , Biologia Computacional/métodos , Mineração de Dados , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Ensaios de Triagem em Larga Escala , Humanos , National Academy of Sciences, U.S. , Relação Estrutura-Atividade , Testes de Toxicidade/tendências , Toxicogenética/métodos , Toxicologia/métodos , Estados UnidosRESUMO
Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.
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Alternativas aos Testes com Animais/normas , Testes Cutâneos/normas , Testes de Toxicidade/normas , Cooperação Internacional , Padrões de ReferênciaRESUMO
Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions.
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Poluentes Atmosféricos/análise , Modelos Teóricos , Solo , Gerenciamento de Resíduos/métodos , Aerossóis , HumanosRESUMO
A series of laboratory-based incubations using a stable isotope tracer technique was applied to measure the net and gross fluxes of CH(3)Cl and CH(3)Br as well as the net fluxes of CHCl(3) from surface soils of the Sacramento-San Joaquin Delta of California. Annually averaged flux measurements show that these mineral/oxidized peat soils are a net source of CH(3)Cl (140 ± 266 nmol m(-2) d(-1)) and CHCl(3) (258 ± 288 nmol m(-2) d(-1)), and a net sink of CH(3)Br (-2.3 ± 4.5 nmol m(-2) d(-1)). Gross CH(3)Cl and CH(3)Br fluxes are strongly influenced by both soil moisture and temperature: gross production rates of CH(3)Cl and CH(3)Br are linearly correlated with temperature, whereas gross consumption rates exhibit Gaussian relationships with maximum consumption at soil moisture levels between 20 and 30% volumetric water content (VWC) and a temperature range of 25 to 35 °C. Although soil moisture and soil temperature strongly affect consumption rates, the range of gross consumption rates overall is limited (-506 ± 176 nmol m(-2) d(-1) for CH(3)Cl and -12 ± 4 nmol m(-2) d(-1) for CH(3)Br) and is similar to rates reported in previous studies. CHCl(3) fluxes are not correlated with methyl halide fluxes, temperature, or soil moisture. The annual emission rates of CHCl(3) from the Sacramento-San Joaquin Delta are found to be a potentially significant local source of this compound.
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Clorofórmio/análise , Hidrocarbonetos Bromados/análise , Cloreto de Metila/análise , Poluentes do Solo/análise , Solo/química , Meio Ambiente , Monitoramento Ambiental , Poluição Ambiental/estatística & dados numéricos , Sphagnopsida , TemperaturaRESUMO
We explore the oft-repeated claim that river water quality in Great Britain is "better now than at any time since the Industrial Revolution". We review available data and ancillary evidence for seven different categories of water pollutants: (i) biochemical oxygen demand (BOD) and ammonia; (ii) heavy metals; (iii) sewage-associated organic pollutants (including hormone-like substances, personal care product and pharmaceutical compounds); (iv) macronutrients (nitrogen and phosphorus); (v) pesticides; (vi) acid deposition and (vii) other variables, including natural organic matter and pathogenic micro-organisms. With a few exceptions, observed data are scarce before 1970. However, we can speculate about some of the major water quality pressures which have existed before that. Point-source pollutants are likely to have increased with population growth, increased connection rates to sewerage and industrialisation, although the increased provision of wastewater treatment during the 20th century will have mitigated this to some extent. From 1940 to the 1990s, pressures from nutrients and pesticides associated with agricultural intensification have increased in many areas. In parallel, there was an increase in synthetic organic compounds with a "down-the-drain" disposal pathway. The 1990s saw general reductions in mean concentrations of metals, BOD and ammonia (driven by the EU Urban Waste Water Treatment Directive), a levelling out of nitrate concentrations (driven by the EU Nitrate Directive), a decrease in phosphate loads from both point-and diffuse-sources and some recovery from catchment acidification. The current picture is mixed: water quality in many rivers downstream of urban centres has improved in sanitary terms but not with respect to emerging contaminants, while river quality in catchments with intensive agriculture is likely to remain worse now than before the 1960s. Water quality is still unacceptably poor in some water bodies. This is often a consequence of multiple stressors which need to be better-identified and prioritised to enable continued recovery.
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Praguicidas , Poluentes Químicos da Água , Poluentes da Água , Amônia , Monitoramento Ambiental , Nitratos , Compostos Orgânicos , Poluentes da Água/análise , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
The forward scattering of light in a conventional inverted optical microscope by nanoparticles ranging in diameter from 10 to 50nm has been used to automatically and quantitatively identify and track their location in three-dimensions with a temporal resolution of 200ms. The standard deviation of the location of nominally stationary 50-nm-diameter nanoparticles was found to be about 50nm along the light path and about 5nm in the plane perpendicular to the light path. The method is based on oscillating the microscope objective along the light path using a piezo actuator and acquiring images with the condenser aperture closed to a minimum to enhance the effects of diffraction. Data processing in the time and spatial domains allowed the location of particles to be obtained automatically so that the technique has potential applications both in the processing of nanoparticles and in their use in a variety of fields including nanobiotechnology, pharmaceuticals and food processing where a simple optical microscope maybe preferred for a variety of reasons.
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Algoritmos , Imageamento Tridimensional/métodos , Microscopia/métodos , Nanopartículas/química , Espalhamento de Radiação , Luz , Microscopia/instrumentação , Nanopartículas/efeitos da radiaçãoRESUMO
Modern conventional farming provides Western Europe and North America with reliable, high quality, and relatively cheap supplies of food and fiber, increasingly viewed as a potential source of fuel. One of the costs is continued widespread pollution of rivers and groundwater-predominantly by nutrients. In 1970, in both the United States and UK, farming was focused on maximizing yield and management practices were rapidly modernizing. Little attention was paid to the external impacts of farming. In 2010, diffuse pollution from agriculture is being seriously addressed by both voluntary and statutory means in an attempt to balance environmental costs with the continued benefits of agricultural production. In this paper we consider long-term changes in the concentration and flux of nitrate in five rural UK rivers to demonstrate the impact of agricultural intensification and subsequent policies to reduce diffuse pollution on river water quality between 1970 and 2010.
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Política Ambiental , Nitratos/análise , Rios/química , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , Monitoramento Ambiental , Reino UnidoRESUMO
Urine patches deposited in pasture by grazing animals are sites of reactive nitrogen (N) loss to the environment due to high concentrations of N exceeding pasture uptake requirements. In order to upscale N losses from the urine patch, several urination parameters are required, including where, when and how often urination events occur as well as the volume and chemical composition. There are limited data available in this respect, especially for sheep. Here, we seek to address this knowledge gap by using non-invasive sensor-based technology (accelerometers) on ewes grazing in situ, using a Boolean algorithm to detect urination events in the accelerometer signal. We conducted an initial study with penned Welsh Mountain ewes (n = 5), with accelerometers attached to the hind, to derive urine flow rate and to determine whether urine volume could be estimated from ewe squat time. Then accelerometers attached to the hind of Welsh Mountain ewes (n = 30 at each site) were used to investigate the frequency of sheep urination events (n = 35 946) whilst grazing two extensively managed upland pastures (semi-improved and unimproved) across two seasons (spring and autumn) at each site (35-40 days each). Sheep urinated at a frequency of 10.2 ± 0.2 and 8.1 ± 0.3 times per day in the spring and autumn, respectively, while grazing the semi-improved pasture. Urination frequency was greater (19.0 ± 0.4 and 15.3 ± 0.3 times per day in the spring and autumn, respectively) in the unimproved pasture. Ewe squat duration could be reliably used to predict the volume of urine deposited per event and was thus used to estimate mean daily urine production volumes. Sheep urinated at a rate of 16.6 mL/s and, across the entire dataset, sheep squatted for an average of 9.62 ± 0.03 s per squatting event, producing an estimated average individual urine event volume of 159 ± 1 mL (n = 35 946 events), ranging between 17 and 745 mL (for squat durations of 1 to 45 s). The estimated mean daily urine volume was 2.15 ± 0.04 L (n = 2 669 days) across the entire dataset. The data will be useful for modelling studies estimating N losses (e.g. ammonia (NH3) volatilisation, nitrous oxide (N2O) emission via nitrification and denitrification and nitrate (NO3-) leaching) from urine patches.
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Nitrogênio , Óxido Nitroso , Acelerometria/veterinária , Amônia , Animais , Feminino , Estações do Ano , OvinosRESUMO
Long records of river water quality are invaluable for helping to understand the biogeochemistry of hydrological systems. They allow relationships to be established between changes in water quality (including seasonal cycles, episodic responses and long-term trends) and potential drivers, such as climatic forcing or human activity; they can act as a stimulus for process-oriented experimental research; they can be used to help to make predictions about future temporal and spatial patterns; and they can help to guide management options to mitigate water pollution. In this paper we present the case in favour of maintaining some long records of river water nitrate concentration at "benchmark" sites, in terms of enhancing process understanding and identifying system lags. Many long-term time series of nitrate concentration data share similar features including a pronounced seasonality characterised by a clear winter maximum, an upward trend in the post-war period followed by a levelling off, or even a decline in the last 20 years, and unusually high concentrations following drought years. Concentrations in any one year are often dependent on conditions in previous years; relationships can be established between concentrations and hydrological drivers (such as rainfall) with different lag periods which can yield information about supply or transport limitations to nitrate transfers. The interpretation of any record is dependent on its length: short records have a high potential for misinterpretation. Often, the value of long records only becomes apparent when analysed in retrospect, perhaps yielding insight into processes and phenomena for which the data collection programme was not originally designed. We, therefore, urge monitoring agencies to devise a strategy for maintaining long records--at least for a few benchmark stations.
Assuntos
Monitoramento Ambiental/métodos , Nitratos/análise , Rios/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/normas , Fatores de Tempo , Abastecimento de Água/análise , Abastecimento de Água/normasRESUMO
The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing. Self-management supported by mobile device applications could improve outcomes for people with COPD. Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care. A systematic review was conducted to identify randomized controlled trials. Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL). Where possible, outcome data were pooled for meta-analyses. Of 1709 citations returned, 13 were eligible trials. Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported. Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant. There was notable variation in outcome measures used across trials. Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research.
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Dispneia/fisiopatologia , Aplicativos Móveis , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Autogestão/métodos , Atividades Cotidianas , Progressão da Doença , Exercício Físico , Estado Funcional , Humanos , Avaliação de Resultados em Cuidados de Saúde , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , AutoeficáciaRESUMO
Pesticide losses from agricultural land to water can result in the environmental deterioration of receiving systems. Mathematical models can make important contributions to risk assessments and catchment management. However, some mechanistic models have high parameter requirements which can make them difficult to apply in data poor areas. In addition, uncertainties in pesticide properties and applications are difficult to account for using models with long run-times. Alternative, simpler, conceptual models are easier to apply and can still be used as a framework for process interpretation. Here, we present a new conceptual model of pesticide behaviour in surface water catchments, based on continuous water balance calculations. Pesticide losses to surface waters are calculated based on the displacement of a limited fraction of the soil pore water during storm events occurring after application. The model was used to describe the behaviour of metaldehyde in a small (2.2 km2) under-drained catchment in Eastern England. Metaldehyde is a molluscicide which has been regularly detected at high concentrations in many drinking water supply catchments. Measured peak concentrations in stream water (to about 9 µg L-1) occurred in the first few storm events after application in mid-August. In each event, there was a quasi-exponential decrease in concentration during hydrograph recession. Peak concentrations decreased in successive events - responding to rainfall but reflecting an effective exhaustion in soil supply due to degradation and dissipation. Uncertain pesticide applications to the catchment were estimated using land cover analysis of satellite data, combined with a Poisson distribution to describe the timing of application. Model performance for both the hydrograph (after calibration of the water balance) and the chemograph was good and could be improved via some minor adjustments in assumptions which yield general insights into the drivers for pesticide transport. The use of remote sensing offers some promising opportunities for estimating catchment-scale pesticide applications and associated losses.
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Agricultura , Praguicidas , Poluentes Químicos da Água , Acetaldeído/análogos & derivados , Inglaterra , Monitoramento Ambiental , Modelos Teóricos , Movimentos da ÁguaRESUMO
In regions of the world with poor provision of wastewater treatment, raw sewage is often discharged directly into surface waters. This paper describes an experimental evaluation of the fate of two organic chemicals under these conditions using an artificial channel cascade fed with a mix of settled sewage and river water at its upstream end and operated under continuous steady-state conditions. The experiments underpin an environmental risk assessment methodology based on the idea of an "impact zone" (IZ) - the zone downstream of wastewater emission in which water quality is severely impaired by high concentrations of unionised ammonia, nitrite and biochemical oxygen demand (BOD). Radiolabelled dodecane-6-benzene sulphonate (DOBS) and aniline hydrochloride were used as the model chemical and reference compound respectively. Rapid changes in (14)C counts were observed with flow-time for both these materials. These changes were most likely to be due to complete mineralisation. A dissipation half-life of approximately 7.1 h was observed for the (14)C label with DOBS. The end of the IZ was defined as the point at which the concentration of both unionised ammonia and nitrite fell below their respective predicted no-effect concentrations for salmonids. At these points in the cascade, approximately 83 and 90% of the initial concentration of (14)C had been removed from the water column, respectively. A simple model of mineral nitrogen transformations based on Michaelis-Menten kinetics was fitted to observed concentrations of NH(4), NO(2) and NO(3). The cascade is intended to provide a confirmatory methodology for assessing the ecological risks of chemicals under direct discharge conditions.
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Poluentes da Água , Água/química , Modelos Químicos , RiosRESUMO
Multi-media fate and transport models (MFTMs) are invaluable tools in understanding and predicting the likely behaviour of organic pollutants in the environment. However, some parameters describing the properties of both the environmental system and the chemical pollutant under consideration are uncertain and or variable in space and time. Furthermore, model performance is often evaluated using sparse data sets on chemical concentrations in different media. This can result in equifinality - the phenomenon in which several different combinations of model parameters can result in similar predictions of environmental concentrations. We explore this idea for MFTMs for the first time using, as examples, three cyclic volatile methyl siloxanes (cVMS: D4, D5 and D6) and the QWASI lake model applied to Tokyo Bay. Monte Carlo simulation was employed with parameters selected from probability distributions representing estimated uncertainty in a large number of iterations. This generated distributions of predicted chemical concentrations in water (CW) and sediment (CS) which represent the aleatory uncertainty envelope but which also demonstrate significant equifinality. For all three compounds, the uncertainty implied in the CW was lower (coefficient of variation, CV, of the order of 20%) than for CS (CV ca. 45%), reflecting the propensity of cVMS compounds to sorb to sediment and the sensitivity of the model to KOC. Confidence intervals were particularly high for the persistence of D5 and D6 in sediment which both ranged between approximately 1.7 years and approximately 26 years for Tokyo Bay. Predicted concentration distributions matched observations well for D5 and D6 not for D4. Equifinality could be reduced by better constraining acceptable parameter sets using additional measured data from different environmental compartments.
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Monitoramento Ambiental/métodos , Modelos Teóricos , Siloxanas/análise , Compostos Orgânicos Voláteis/análise , Poluentes Químicos da Água/análise , Baías/química , Monitoramento Ambiental/estatística & dados numéricos , Japão , Lagos/química , Método de Monte Carlo , IncertezaRESUMO
A national approach to addressing sexually transmitted and blood-borne infections (STBBIs) was recently articulated in the Public Health Agency of Canada's new A Pan-Canadian Framework for Action: Reducing the health impact of sexually transmitted and blood-borne infections in Canada by 2030. This Framework promotes an integrated approach, with a focus on the key populations that are affected by overlapping epidemics (i.e., syndemics). We advance the idea that integrating surveillance would be helpful in characterizing and understanding the populations, locations, risk behaviours and other drivers that contribute to STBBI syndemics. The creation of matched or linked data systems that would allow routine reporting of integrated data is challenged by the technical barriers of integrating data silos as well as by the privacy and ethical considerations of merging sensitive individual-level data. Lessons can be learned from jurisdictions where an improved understanding of syndemics, through integrated STBBI surveillance, has led to more efficient and effective operational, program and policy decisions. Emerging enablers include the development of data standards and guidelines, investment in resources to overcome technical challenges and community engagement to support the ethical and non-stigmatizing use of integrated data. The Framework's call to action offers an opportunity for national discussion on priorities and resources needed to advance STBBI syndemic surveillance for local, regional and national reporting in Canada.
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We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56+ and CD56- fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.
Assuntos
Antígenos de Helmintos/imunologia , Antígenos Virais/imunologia , Proteínas de Helminto/imunologia , Hepacivirus/imunologia , Subpopulações de Linfócitos/imunologia , Toxoide Tetânico/imunologia , Adjuvantes Imunológicos , Adulto , Idoso , Antígeno CD56/análise , Comunicação Celular/imunologia , Células Cultivadas , Citocinas/biossíntese , Feminino , Hepatite C Crônica/imunologia , Humanos , Memória Imunológica , Mediadores da Inflamação/metabolismo , Interferon gama/biossíntese , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologiaRESUMO
BACKGROUND: Influenza outbreaks in hospital settings affect vulnerable patient populations and pose considerable risk of morbidity and mortality; however, key information regarding these outbreaks is limited. OBJECTIVE: To describe surveillance data on influenza outbreaks in Ontario hospitals between 2012-13 and 2015-16 and compare H3N2- and H1N1-dominant influenza seasons. METHODS: Hospital laboratory-confirmed influenza outbreaks occurring between September 1, 2012 and August 31, 2016 were analysed for indicators of outbreak duration and severity (case attack rate, pneumonia rate and fatality rate). Frequency, duration and severity of influenza A outbreaks were compared between H3N2- (2012-13, 2014-15) and H1N1-dominant seasons (2013-14, 2015-16). RESULTS: Over the four years, there were 256 hospital outbreaks involving 1,586 patients that included 91 cases of pneumonia and 40 deaths. The total number of outbreaks was lowest in the 2015-16 (n=36) and highest in the 2014-15 (n=117) influenza seasons. The 2014-15 season also had the highest number of influenza cases (n=753), pneumonia cases (n=46), fatalities (n=18) and hospital sites reporting ≥1 outbreak (n=72). Median outbreak duration ranged from 4.5 days in 2013-14 to 6.0 days in 2015-16. Comparisons of H3N2 and H1N1 seasons did not identify statistically significant differences in outbreak duration or severity; however, significantly more influenza A outbreaks than influenza B outbreaks were reported in H3N2 seasons compared with H1N1 seasons (p<0.05). CONCLUSION: While H3N2-dominant years contribute to influenza morbidity and mortality through an increased number of hospital outbreaks, the duration and severity of influenza A outbreaks are not significantly different in H3N2 and H1N1 seasons.
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This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from the reductionist nature of an alternative test as compared to the animal study as well as from the animal study being considered as the gold standard. Modern approaches combine individual alternatives into testing strategies, for which integrated and defined approaches are emerging at OECD. Furthermore, progress in mechanistic toxicology, e.g. through the adverse outcome pathway approach, and in computational systems toxicology allows integration of alternative test battery results into toxicity predictions that are more fine-tuned to the human situation. The road towards transition to a mechanistically-based human-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment.
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Alternativas aos Testes com Animais/métodos , Medição de Risco/métodos , Testes de Toxicidade/métodos , Animais , Órgãos Governamentais , Humanos , Reprodutibilidade dos TestesRESUMO
Direct discharge of untreated sewage to surface waters is a common practice in many parts of the world. However, relatively little is known about the behaviour of synthetic organic pollutants under these conditions. This paper describes a sampling campaign designed to track changes in water quality in a surface water system in Vientiane (Lao PDR) receiving significant quantities of untreated waste water. The study was based on following in-channel transport using a fluorescent tracer injected as a pulse, with a focus on the anionic surfactant linear alkylbenzene sulphonate (LAS) and ammonia. Water samples were collected at a number of stations with sampling times estimated to coincide with solute time-of-travel. The reduction in LAS concentration with flow-time could be approximated by first-order kinetics with a half life of about 7 h. Free ammonia concentrations decreased more slowly than LAS and remained above the level believed to be toxic for sensitive aquatic species along the entire channel. Changes in the ratios of LAS alkyl chain homologues to total LAS concentrations suggest a preferential removal of longer chain lengths. The role of biodegradation in the removal of LAS was confirmed by the presence of LAS metabolites (sulphophenylcarboxylates, SPCs) which increased systematically (as a fraction of LAS remaining) with flow-time.