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The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.
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Imagem de Difusão por Ressonância Magnética , Substância Branca , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Substância Branca/diagnóstico por imagem , Fibras Nervosas , Visão Ocular , Tálamo , Anisotropia , Vias Visuais/diagnóstico por imagemRESUMO
The current work is an attempt to reveal the possible utilization of the radiometric measurements to build-up a complete genetic scenario for magmatic, hydrothermal, and supergene uranium mineralization. For this purpose, ground gamma-ray survey was performed through the exploratory tunnels dug perpendicular to El-Missikat and El-Erediya shear zones, the Central Eastern Desert of Egypt. Contents of U, Th, and K were measured for the host pink granite (e.g., avg.15.94 U ppm, 35.62 Th ppm, and 6.63% K), alteration zones (brecciation, silicification, greisenization, kaolinization and hematitization) (e.g., avg. 124.01 U ppm, 63.67 Th ppm, and 3.13% K), and mineralized silica veins (e.g., avg. 312.65 U ppm, 92.22 Th ppm, and 2.62% K). All of these data were graphically represented as correlation plots of Th vs. U, Th/U vs. U, Th vs. K, and U/K vs. Th/K. The overall results indicate magmatic, hydrothermal, and supergene sources of El-Missikat and El-Erediya U mineralization. The magma-derived U contents are enclosed mainly in the pink granite that is mostly characterized by normal Th/U (2.5-5) and Th/K ratios (3-5*10-4). The hydrothermal processes through the alteration zones and mineralized silica veins are reflected by the weak correlation of Th with U (e.g. r = 0.13 and - 0.39), the strong negative correlation of Th/U ratio with U (e.g. r = - 0.82), 2.5ËTh/UË0.1, Th/KË5*10-4, Th/K < 3*10-4, and the strong positive correlation of U/K with Th/K (e.g. r = 0.91) as well as the occurrence of thorite, columbite, xenotime and hydrothermal zircon (0.5 > Th/U ≤ 0.1). Afterwards, the hydrothermal mineralization underwent some degrees of chemical weathering that resulted in supergene U mineralization whose fingerprints can be traced by the occurrence of secondary U minerals (e.g. kasolite and uranophane), Th/U ratios ≤ 0.1, and the weak correlation between Th/K and U/K (e.g. r = 0.39 and - 0.11).
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Historical PM2.5 data are essential for assessing the health effects of air pollution exposure across the life course or early life. However, a lack of high-quality data sources, such as satellite-based aerosol optical depth before 2000, has resulted in a gap in spatiotemporally resolved PM2.5 data for historical periods. Taking the United Kingdom as an example, we leveraged the light gradient boosting model to capture the spatiotemporal association between PM2.5 concentrations and multi-source geospatial predictors. Augmented PM2.5 from PM10 measurements expanded the spatiotemporal representativeness of the ground measurements. Observations before and after 2009 were used to train and test the models, respectively. Our model showed fair prediction accuracy from 2010 to 2019 [the ranges of coefficients of determination (R2) for the grid-based cross-validation are 0.71-0.85] and commendable back extrapolation performance from 1998 to 2009 (the ranges of R2 for the independent external testing are 0.32-0.65) at the daily level. The pollution episodes in the 1980s and pollution levels in the 1990s were also reproduced by our model. The 4-decade PM2.5 estimates demonstrated that most regions in England witnessed significant downward trends in PM2.5 pollution. The methods developed in this study are generalizable to other data-rich regions for historical air pollution exposure assessment.
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Poluentes Atmosféricos , Poluição do Ar , Material Particulado/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar/análise , Aprendizado de Máquina , Reino UnidoRESUMO
The increasing threat of cyberattacks has resulted in increased efforts by both the U.K. government and regulatory authorities to coordinate efforts to influence cybersecurity risk management practices in the U.K. insurance sector, focusing on cyber risk underwriters. This paper provides an evaluation of these arrangements. It first provides a descriptive overview of the key U.K. regulatory authorities and the evolution of their efforts over the past decade, as well as the scope for broader collaborations with industry and member-based associations and international organisations. It then evaluates the effectiveness of these efforts by providing a multi-method study of the incidence, nature and evolution of cost of data breaches, investment in computer systems and software intangible assets at risk of cyberattack, and a content analysis of annual reports of both U.K. regulators and a sample of U.K. insurers. The findings suggest that while both the total costs of data breaches and the size of investment in computer systems and software intangibles at risk of cyberattack have gradually increased over time, the degree of engagement with cyber as a reporting issue by both cyber insurers and financial regulators has not. It is concluded that while these efforts have been apparently successful in avoiding a large-scale, systemic cyberattack on the U.K. insurance industry, there are significant gaps and overlaps in the system of cyber regulatory oversight.
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The United Kingdom (UK) was among the hardest-hit by the COVID-19 pandemic. It is, therefore, imperative to understand the coping strategies of individuals in the UK during the pandemic to develop appropriate programs and policies for them. A heterogeneous sample of 50 UK residents (15 males & 35 females) with an age range of 18-55 years were recruited using a snowball technique from Facebook between April and May 2020. Participants responded to 4 open-ended questions (that were generated through consultation with literature and 2 health practitioners) that sought to explore their coping strategies during the COVID-19 pandemic. Thematic analysis was applied to analyze data using a data-driven method. Eleven themes were found: "socializing with loved ones (e.g., through video calls)", "engaging in exercise", "being occupied with jobs", "being occupied with studies", "avoiding negative news on COVID-19", "consumption of alcohol", "healthy eating", "engaging in meditation activities", "gaming activities", "hope", and "self-care and self-appreciation", in that order. Positive and maladaptive coping strategies were employed by some individuals in the UK during the COVID-19 pandemic. This, therefore, echoes the need for appropriate psychosocial support programs that strengthen positive coping strategies and mitigate maladaptive coping strategies during the COVID-19 pandemic.
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Deriving reliable information about the structural and functional architecture of the brain in vivo is critical for the clinical and basic neurosciences. In the new era of large population-based datasets, when multiple brain imaging modalities and contrasts are combined in order to reveal latent brain structural patterns and associations with genetic, demographic and clinical information, automated and stringent quality control (QC) procedures are important. Diffusion magnetic resonance imaging (dMRI) is a fertile imaging technique for probing and visualising brain tissue microstructure in vivo, and has been included in most standard imaging protocols in large-scale studies. Due to its sensitivity to subject motion and technical artefacts, automated QC procedures prior to scalar diffusion metrics estimation are required in order to minimise the influence of noise and artefacts. However, the QC procedures performed on raw diffusion data cannot guarantee an absence of distorted maps among the derived diffusion metrics. Thus, robust and efficient QC methods for diffusion scalar metrics are needed. Here, we introduce Fast qualitY conTrol meThod foR derIved diffUsion Metrics (YTTRIUM), a computationally efficient QC method utilising structural similarity to evaluate diffusion map quality and mean diffusion metrics. As an example, we applied YTTRIUM in the context of tract-based spatial statistics to assess associations between age and kurtosis imaging and white matter tract integrity maps in U.K. Biobank data (n = 18,608). To assess the influence of outliers on results obtained using machine learning (ML) approaches, we tested the effects of applying YTTRIUM on brain age prediction. We demonstrated that the proposed QC pipeline represents an efficient approach for identifying poor quality datasets and artefacts and increases the accuracy of ML based brain age prediction.
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Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/normas , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Bancos de Espécimes Biológicos , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Controle de Qualidade , Reino UnidoRESUMO
Parkinson's disease (PD) is a chronic movement disorder that produces a variety of characteristic movement abnormalities. The ubiquity of wrist-worn accelerometry suggests a possible sensor modality for early detection of PD symptoms and subsequent tracking of PD symptom severity. As an initial proof of concept for this technological approach, we analyzed the U.K. Biobank data set, consisting of one week of wrist-worn accelerometry from a population with a PD primary diagnosis and an age-matched healthy control population. Measures of movement dispersion were extracted from automatically segmented gait data, and measures of movement dimensionality were extracted from automatically segmented low-movement data. Using machine learning classifiers applied to one week of data, PD was detected with an area under the curve (AUC) of 0.69 on gait data, AUC = 0.84 on low-movement data, and AUC = 0.85 on a fusion of both activities. It was also found that classification accuracy steadily improved across the one-week data collection, suggesting that higher accuracy could be achievable from a longer data collection. These results suggest the viability of using a low-cost and easy-to-use activity sensor for detecting movement abnormalities due to PD and motivate further research on early PD detection and tracking of PD symptom severity.
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Acelerometria/instrumentação , Doença de Parkinson/diagnóstico , Tremor/diagnóstico , Dispositivos Eletrônicos Vestíveis , Acelerometria/métodos , Adulto , Idoso , Bancos de Espécimes Biológicos , Marcha/fisiologia , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Monitorização Fisiológica , Doença de Parkinson/fisiopatologia , PunhoRESUMO
The red sheep tick, Haemaphysalis punctata (Ixodida: Ixodidae), has been reported as present in the U.K. for more than a century; however, very little has been written about its distribution. In recent years, numbers of detections of this tick species reported to the Public Health England (PHE) Tick Surveillance Scheme have increased. This rise in the number of records may be attributable to increased tick surveillance activities or to the increased distribution of this species of tick in parts of England. This paper reviews published reports of H. punctata and all data held by the Biological Records Centre and PHE, and summarizes a number of field studies conducted by PHE and the Animal and Plant Health Agency over the past 8 years. It would appear from the evidence presented here that H. punctata may be expanding its range across the eastern part of the South Downs National Park, where there have also been reports of this tick species biting humans. It is possible that the movement of sheep between grassland sites is facilitating this spread. Further studies that better elucidate the ecology of this tick and its possible role as a vector of human and veterinary diseases are now warranted.
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Doenças das Aves/parasitologia , Ixodidae/fisiologia , Passeriformes/parasitologia , Coelhos/parasitologia , Doenças dos Ovinos/parasitologia , Infestações por Carrapato/veterinária , Animais , Doenças das Aves/epidemiologia , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Poaceae/parasitologia , Ovinos , Doenças dos Ovinos/epidemiologia , Infestações por Carrapato/epidemiologia , Infestações por Carrapato/parasitologia , País de Gales/epidemiologiaRESUMO
The recent implication of Dermacentor reticulatus (Ixodida: Ixodidae) in the transmission of canine babesiosis in the U.K. has highlighted the lack of accurate published data on its distribution in this country. This paper aims to collate and appraise historical data for D. reticulatus, to supplement such data with more recent surveillance data and to report on field sampling conducted during 2009-2016. These updated data facilitate better understanding of the current distribution of this tick in the U.K., which will better inform disease risk assessments. There appear to be four known regions of the U.K. in which D. reticulatus currently occurs, including western Wales, North and South Devon, and Essex. The majority of foci are located in coastal sand dunes and maritime grasslands, including grazing marsh. However, more recently the tick has been detected in urban greenspace in Essex. The emergence of this tick as a vector of babesiosis in the U.K. and its recent apparent spread in Essex into urban greenspace highlight the need for continued surveillance and for further research into its status as a vector of human and veterinary pathogens.
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Distribuição Animal , Vetores Aracnídeos/fisiologia , Dermacentor/fisiologia , Animais , Vetores Aracnídeos/crescimento & desenvolvimento , Dermacentor/crescimento & desenvolvimento , Cães , Inglaterra , Feminino , Larva/crescimento & desenvolvimento , Larva/fisiologia , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , País de GalesRESUMO
Remarkable progress has been made over the past decade in cancer medicine. Personalized medicine, driven by biomarker predictive factors, novel biotherapy, novel imaging, and molecular targeted therapeutics, has improved outcomes. Cancer is becoming a chronic disease rather than a fatal disease for many patients. However, despite this progress, there is much work to do if patients are to receive continuous high-quality care in the appropriate place, at the appropriate time, and with the right specialized expert oversight. Unfortunately, the rapid expansion of therapeutic options has also generated an ever-increasing burden of emergency care and encroaches into end-of-life palliative care. Emergency presentation is a common consequence of cancer and of cancer treatment complications. It represents an important proportion of new presentations of previously undiagnosed malignancy. In the U.K. alone, 20%-25% of new cancer diagnoses are made following an initial presentation to the hospital emergency department, with a greater proportion in patients older than 70 years. This late presentation accounts for poor survival outcomes and is often associated with poor patient experience and poorly coordinated care. The recent development of acute oncology services in the U.K. aims to improve patient safety, quality of care, and the coordination of care for all patients with cancer who require emergency access to care, irrespective of the place of care and admission route. Furthermore, prompt management coordinated by expert teams and access to protocol-driven pathways have the potential to improve patient experience and drive efficiency when services are fully established. The challenge to leaders of acute oncology services is to develop bespoke models of care, appropriate to local services, but with an opportunity for acute oncology teams to engage cancer care strategies and influence cancer care and delivery in the future. This will aid the integration of highly specialized cancer treatment with high-quality care close to home and help avoid hospital admission.
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Serviços Médicos de Emergência , Neoplasias/mortalidade , Neoplasias/terapia , Serviço Hospitalar de Oncologia , Medicina de Precisão , Humanos , Prognóstico , Reino UnidoRESUMO
Mosquitoes of the Anopheles maculipennis Meigen (Diptera: Culicidae) group are of public health concern: five of the 11 morphologically indistinct species have been historically considered as vectors of malaria in Europe. Three members of the An. maculipennis group have been reported in the U.K.: Anopheles atroparvus van Thiel; Anopheles messeae Falleroni, and Anopheles daciae Linton, Nicolescu & Harbach. To study the distribution of the three U.K. species, particularly that of An. daciae, we developed a polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) assay using the nuclear ribosomal internal transcribed spacer 2 (ITS-2) gene. Anopheles daciae was found to be widespread, occurring in four of the five counties surveyed in southern England and on the Welsh island of Anglesey, often in sympatry with the closely related species An. messeae. The host preferences of 237 blood-fed females were determined using either direct sequencing or PCR-based fragment analysis of the mitochondrial cytochrome oxidase b gene with DNA from females' abdomens. All three species were found to be opportunistic, having fed on at least three different hosts. Seventeen individuals contained multiple bloodmeals, including two An. daciae that had fed on humans and birds. Our results show that An. daciae is widespread in England and Wales, occurs in sympatry with other members of the An. maculipennis group, and feeds on humans, which suggests it is a potential vector of disease in the U.K.
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Distribuição Animal , Anopheles/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Insetos Vetores/fisiologia , Animais , Anopheles/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Inglaterra , Comportamento Alimentar , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/genética , Malária/transmissão , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , País de GalesRESUMO
BACKGROUND: Previous studies have shown that respiratory diseases are associated with an increased risk of rheumatoid arthritis (RA). However, whether there is a correlation between chronic rhinosinusitis (CRS) and RA is not known. Due to the high incidence of CRS, it remains to be clarified whether we should pay additional attention to RA risk in the huge population of CRS. METHODS: We used a 2-sample Mendelian randomization (MR) analysis to explore the causal effects of CRS on the incidence of RA. The inverse variance weighted (IVW) approach was used as the main analysis in the MR randomization study. Then, we used the data from the U.K. Biobank to examine the association between RA and CRS at the individual level in a prospective cohort. We identified patients with CRS at the time of recruitment and further followed the incidence of RA until 2021. The risk of developing RA in patients with CRS was determined by a multivariate Cox regression model. We used 3 multivariate Cox models to adjust for individual characteristics, lifestyle factors and concomitant diseases, respectively. RESULTS: The MR analysis by the IVW model suggested that the odds ratio of RA associated with genetically predicted CRS was 2.39 (95% CI [1.08-5.30]; p = .032). In the first multivariate model adjusting for individual characteristics, CRS was associated with a 47% increase of risk of developing RA (hazard ratio [HR] = 1.47; 95% CI [1.12-1.90]). In the second multivariate model adjusting for lifestyle factors, the HR of RA associated with CRS was 1.48 (95% CI [1.15-1.90]). In the third multivariate model, chronic sinusitis was associated with a 32% increase in RA risk (HR = 1.32; 95% CI [1.03-1.70]). CONCLUSION: CRS has a genetically causal effect on the incidence of RA, and the risk of RA is greatly higher in CRS at the individual level. This is the first study to reveal an association between CRS and RA. Due to the high incidence of CRS, it is recommended that additional attention should be paid to the increased RA risk in patients with CRS compared to that in common people.
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Artrite Reumatoide , Rinossinusite , Sinusite , Humanos , Bancos de Espécimes Biológicos , Análise da Randomização Mendeliana , Doença Crônica , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to a paradigm shift in global health, casting a previously niche academic discipline into a headline dominating field of research. However, accurate information on the delivery of global health education (GHE) at a university level is lacking. This study aims to assess current GHE practices in U.K. universities, by identifying the availability of dedicated global health qualifications, as well as the breadth of inclusion of GHE topics across university course content. METHODS: Universities selected were the top 25 recipients of MRC funding in 2015-2016, as well as universities who were included in previous iterations of the "Global Health League Table". We used the Consortium of Universities for Global Health "GHE Competencies Toolkit" to identify the presence of global health content across university global health and other course offerings. Universities were additionally judged on opportunities available in global health and on the presence of sustainable partnerships. RESULTS: Our results showed that 20 universities (74%) offer a post-graduate global health related course, with 9 (33%) offering an undergraduate global health related course. 13 (48%) were identified as centers of global health excellence. Just 12 (44%) universities had registered sustainable partnerships with Tropical Health and Education Trust. The London School of Hygiene and Tropical Medicine was identified as the top deliverer of GHE, with the Universities of Leicester and the Universities of Exeter joint bottom. We were unable to standardize quality assessments in this iteration of the project, but the release of student feedback to future assessors would help to improve the reliability of this study methodology. Additionally, much of our data was based on information available online, and thus some aspects of degree courses not published publicly may not have been accounted for in our scoring. CONCLUSION: Those institutions wishing to improve their delivery of GHE should consider the establishment of a postgraduate or undergraduate degree course. Breadth of global health content across curricular was a major discriminating factor between institutions, and we would advise universities to consider including more global health topics across their curricular - especially in light of the intersectional impacts of the COVID-19 pandemic.
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Introduction: Many SARS-CoV-2 variants of concern (VOC) have been reported recently that were linked to increased transmission. In our earlier study using VOC 202012/01 (U.K. variant) and D614G variant in the hamster model, we observed higher viral RNA shedding through nasal wash in the case of U.K. variant with lower pathogenicity in lung. In this study, we have studied transmission of these two variants by direct contact, aerosol, and fomite routes in Syrian hamsters and compared the viral load and body weight changes in hamsters exposed by both variants to understand the transmission efficiency. Methods: Nasal, throat, and rectal swabs were collected sequentially to assess viral load till 14 days. Results: Transmission could be established by direct, aerosol, and fomite contact in Syrian hamsters. Body weight loss or viral load in the contact animals exposed did not show any statistical significance. Conclusion: The study demonstrated comparable transmission of both U.K. and D614G variants of SARS-CoV-2 in Syrian hamsters in the given conditions. Provided these data, it seems that all the routes of exposure are effective leading to higher transmission.
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COVID-19/transmissão , COVID-19/virologia , SARS-CoV-2/classificação , Aerossóis , Animais , Cricetinae , Modelos Animais de Doenças , Fômites/virologia , Anticorpos Anti-HIV/análise , Imunoglobulina G/análise , Pulmão , Masculino , Mesocricetus , Cavidade Nasal/virologia , Faringe/virologia , RNA Viral/análise , Reto/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Reino Unido , Carga Viral , Redução de PesoRESUMO
Coronavirus disease 2019 has changed the way the world is navigated and has had a massive impact on health care. Depending on where you are in the world, the guidance on dealing with potential infected patients is varied. With the high risk of a second wave, it is important to learn from initial responses to plan for the future. With proper preparation, it is possible to minimize exposure and risk of contamination to individuals visiting molecular imaging departments. Such precautions will help departments operate at full capacity. From the widespread nature of this pandemic, a global perspective can be useful; what follows is the United Kingdom's perspective.
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Infecções por Coronavirus/epidemiologia , Departamentos Hospitalares/normas , Imagem Molecular/normas , Pneumonia Viral/epidemiologia , COVID-19 , Humanos , Pandemias , Padrões de Referência , Reino Unido , Recursos Humanos/estatística & dados numéricosRESUMO
This paper aims to introduce our publicly available datasets in the area of tourism demand prediction for future experiments and comparisons. Most of the previous works in the area of tourism demand forecasting are based on coarse-grained analysis (level of countries or regions) and there are very few works and consequently datasets available for fine-grained tourism analysis (level of attractions and points of interest). In this article, we present our fine-grained enriched datasets for two types of attractions - (I) indoor attractions (27 Museums and Galleries in U.K.) and (II) outdoor attractions (76 U.S. National Parks) enriched with official number of visits, social media reviews and environmental data for each of them. In addition, the complete analysis of prediction results, methodology and exploited models, features' performance analysis, anomalies, etc, are available in our original paper, "Fine-grained tourism prediction: Impact of social and environmental features"[2].
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LRRK2 mutations cause Parkinson's, but the molecular link from increased kinase activity to pathological neurodegeneration remains undetermined. Previous in vitro assays indicate that LRRK2 substrates include at least 8 Rab GTPases. We have now examined this hypothesis in vivo in a functional, electroretinogram screen, expressing each Rab with/without LRRK2-G2019S in selected Drosophila dopaminergic neurons. Our screen discriminated Rab10 from Rab3. The strongest Rab/LRRK2-G2019S interaction is with Rab10; the weakest with Rab3. Rab10 is expressed in a different set of dopaminergic neurons from Rab3. Thus, anatomical and physiological patterns of Rab10 are related. We conclude that Rab10 is a valid substrate of LRRK2 in dopaminergic neurons in vivo We propose that variations in Rab expression contribute to differences in the rate of neurodegeneration recorded in different dopaminergic nuclei in Parkinson's.
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Drosophila , Doença de Parkinson , Animais , Neurônios Dopaminérgicos/metabolismo , Drosophila/genética , Drosophila/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Mutação , Doença de Parkinson/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Deoxynivalenol (DON) is a toxic fungal metabolite that frequently contaminates cereal crops. DON is toxic to animals, but the effects on humans are poorly understood, in part because exposure estimates are of limited precision. OBJECTIVES: In this study we used the U.K. adult National Diet and Nutrition Survey to compare 24-hr urinary DON excretion with cereal intake. METHODS: One hundred subjects were identified for each of the following cereal consumption groups: low (mean, 107 g cereal/day; range, 88-125), medium (mean, 179 g/day; range, 162-195) and high (mean, 300 g/day; range, 276-325). DON was analyzed in 24-hr urine samples by liquid chromatography-mass spectrometry after purification on immunoaffinity columns. RESULTS: DON was detected in 296 of 300 (98.7%) urine samples. Cereal intake was significantly associated with urinary DON (p < 0.0005), with the geometric mean urinary levels being 6.55 microg DON/day [95% confidence interval (CI), 5.71-7.53]; 9.63 microg/day (95% CI, 8.39-11.05); and 13.24 microg/day (95% CI, 11.54-15.19) for low-, medium-, and high-intake groups, respectively. In multivariable analysis, wholemeal bread (p < 0.0005), white bread (p < 0.0005), "other" bread (p < 0.0005), buns/cakes (p = 0.003), high-fiber breakfast cereal (p = 0.016), and pasta (p = 0.017) were significantly associated with urinary DON. Wholemeal bread was associated with the greatest percent increase in urinary DON per unit of consumption, but white bread contributed approximately twice as much as wholemeal bread to the urinary DON levels because it was consumed in higher amounts. CONCLUSION: The majority of adults in the United Kingdom appear to be exposed to DON, and on the basis of the urinary levels, we estimate that some individuals may exceed the European Union (EU) recommended maximum tolerable daily intake of 1,000 ng DON/kg (bw). This exposure biomarker will be a valuable tool for biomonitoring as part of surveillance strategies and in etiologic studies of DON and human disease risk.
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Pão , Grão Comestível , Tricotecenos/urina , Adulto , Biomarcadores/urina , Monitoramento Ambiental , Feminino , Contaminação de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
We have compared and assessed the suitability of several chromatographic methods for the analysis of long chain alkenones and long chain diols and the associated paleotemperature proxies (UK'37 and LDI). We evaluated the traditional methods for the analysis of the UK'37 and the LDI, gas chromatography (GC) - flame ionization detection (FID) and GC mass spectrometry (MS) using selected ion monitoring (SIM), respectively, and developed a new method using GC-MS/MS in multiple reaction monitoring mode (MRM) for the analysis of long chain diols as well as a method for automatic silylation of diols using a robot autosampler. Finally, we evaluated liquid chromatography (LC) methods to simultaneously measure the UK'37 and the LDI, using ultra high performance LC (UHPLC) with low (nominal mass) resolution MS in SIM mode, and UHPLC with high resolution MS (HRMS). Detection and quantification limits and reproducibility were assessed by means of serial dilutions of culture extracts. Automated silylation by a robot autosampler showed similar reproducibility as off-line silylation while substantially decreasing sample preparation time. The novel MRM method had a slightly lower limit of quantification (LOQ; i.e. 0.3pgC28 1,13-diol injected on-column) than the traditional method (0.5pg) and improved reproducibility while allowing more unambiguous identification of LCDs in complex matrices. For diols, UHPLC-MS using SIM had the highest LOQ (i.e. 15pg) and a comparable reproducibility as GC-MS. UHPLC-HRMS had a LOQ of ca. 1.5pg, and an improved reproducibility for diol analysis. For alkenone analysis, both UHPLC-HRMS and UHPLC-MS using SIM were 2-3 orders of magnitude more sensitive (LOQ ca. 20 and 2pgC37:2 alkenone injected on-column, respectively) than GC-FID (LOD ca. 3ng), with a similar reproducibility of the UK'37 index. Hence, UHPLC-HRMS allows simultaneous analysis of the UK'37 and LDI at an increased sensitivity. In addition, it allows simultaneous measurement of TEX86, a temperature proxy based on the isoprenoid glycerol dialkyl glycerol tetraethers. This reduces the preparation time by excluding the need of derivatization and separation of the ketone (containing the long chain alkenones) and polar fractions (containing the long chain diols and GDGTs). However, synthetic standards are required to fully assess the accuracy of the new methods for determination of the LDI and UK'37.