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1.
Philos Trans R Soc Lond B Biol Sci ; 378(1889): 20220400, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37718599

RESUMO

The potential for changes in water management regimes to reduce greenhouse gases (GHG) in rice paddies has recently become a major topic of research in Asia, with implications for top-down versus bottom-up management strategies. Flooded rice paddies are a major source of anthropogenic GHG emissions and are responsible for approximately 11% of global anthropogenic methane (CH4) emissions. However, rice is also the most important food crop for people in low- and lower-middle-income countries. While CH4 emissions can be reduced by lessening the time the plants are submerged, this can trigger increased emissions of nitrous oxide (N2O), a more potent GHG. Mitigation options for CH4 and N2O are different, and minimizing one gas may increase the emission of the other. Accurate measurement of these gas emissions in rice paddies is difficult, and the results are controversial. We analysed these trade-offs using continuous high-precision measurements in a closed chamber in 2018-2020. Based on the results, we tested a bottom-up adaptive irrigation regime that improves nitrogen uptake by rice plants while reducing combined GHG emissions and nitrogen runoff from paddies to reefs in agricultural drainages. In 2023, we undertook a follow-up study in which farmers obtained higher rice yields with adaptive intermittent irrigation compared to uniformly flooded fields. These results use the polycentric, self-governing capacity of Balinese subaks for continuous adaptation. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.


Assuntos
Gases de Efeito Estufa , Oryza , Humanos , Fazendeiros , Seguimentos , Nitrogênio
2.
J Psychopharmacol ; 37(6): 577-589, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37165642

RESUMO

BACKGROUND: Up to 40% of patients suffering from anxiety disorders do not benefit from currently available pharmacological treatments. Overactivity of the orexin-1 receptor (OX1R) has been implicated in anxiety- and panic-related states. AIM & METHODS: We investigated the pharmacokinetics and characterized the pharmacodynamic (PD) profile of the OX1R antagonist JNJ-61393215 using a battery of central nervous system assessments investigating relevant functional domains such as alertness, attention, (visuo)motor coordination, balance, subjective effects and resting-state electroencephalography in a single ascending dose placebo-controlled study in doses from 1 to 90 mg inclusive, assessing PD up to 10 h after dosing, safety and pharmacokinetic in 48 healthy male subjects. RESULTS: Average time to maximal plasma concentration (Tmax) ranged between 1.0 and 2.25 h; average half-life ranged from 13.6 to 24.6 h and average maximum plasma concentration ranged from 1.4 to 136.8 ng/mL in the 1 and 90 mg groups, respectively. JNJ-61393215 did not demonstrate any statistically significant or clinically meaningful effects on any PD endpoint at any dose investigated at Tmax nor over the total period up to 10 h post-dose and was well tolerated. The reported somnolence rate was 16.7% (which was attributable to the cohorts receiving 6 mg and higher doses) compared to 12.5% in placebo. CONCLUSION: This observation is in line with our knowledge about the OX1R in preclinical studies, where only inconsistent and non-dose-dependent changes in electroencephalography or other behavioural measures were observed under non-challenged conditions, potentially exemplifying the need for a challenged subject.


Assuntos
Antagonistas dos Receptores de Orexina , Humanos , Masculino , Área Sob a Curva , Relação Dose-Resposta a Droga , Método Duplo-Cego , Meia-Vida , Voluntários Saudáveis , Antagonistas dos Receptores de Orexina/efeitos adversos , Antagonistas dos Receptores de Orexina/farmacocinética , Orexinas
4.
Int J Hyg Environ Health ; 242: 113972, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35453051

RESUMO

The Flemish Environment and Health Study (FLEHS) collects information on internal exposure to a broad range of environmental chemicals in the general population in Flanders, the Northern region of Belgium. The aim is to establish biomonitoring exposure distributions for the general population in support of public health and environmental policy, environmental risk assessment and risk management decisions. In 2017-2018, urine and blood samples were collected from 428 teenagers by a stratified clustered two stage randomized design. Samples were analyzed for a broad range of biomarkers related to exposure to chlorinated and newer pesticides, brominated and organophosphate flame retardants (BFR/OPFR), polychlorinated biphenyls (PCBs), bisphenols, phthalates and alternative plasticizers, per-and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), benzene, metals and trace elements. The geometric mean levels and percentiles of the distribution were estimated for each biomarker, for the whole study population and following stratification for sex, the household educational attainment and the residence area's urbanicity. Geometric means of biomarkers of lead, dichlorodiphenyltrichloroethane (DDT), PCBs, PAHs, regulated phthalates and bisphenol A (BPA) were lower than in the previous FLEHS cycles. Most biomarker levels were below health-based guidance values (HB-GVs). However, HB-GVs of urinary arsenic, blood lead, blood cadmium, sum of serum perfluorooctane sulfonate (PFOS) and perfluoro-1-hexanesulfonate (PFHxS) and the urinary pyrethroid metabolite (3-PBA) were exceeded in respectively 25%, 12%, 39.5%, 10% and 22% of the teenagers. These results suggest that the levels of exposure in the Flemish population to some environmental chemicals might be of concern. At the same time, we noticed that biomarkers for BPA substitutes, metabolites of OPFRs, an expanded list of PFAS, glyphosate and its metabolite could be measured in substantial proportions of participants. Interpretation of these levels in a health-risk context remains uncertain as HB-GVs are lacking. Household educational attainment and residential urbanicity were significant exposure determinants for many biomarkers and could influence specific biomarker levels up to 70% as shown by multiple regression analysis. The research consortium also took care of the broader external communication of results with participants, policy makers, professional groups and civil society organizations. Our study demonstrated that teenagers are exposed to a wide range of chemicals, it demonstrates the success of public policies to reduce exposure but also points to concern and further priorities and needs for follow up.


Assuntos
Poluentes Ambientais , Fluorocarbonos , Bifenilos Policlorados , Adolescente , Biomarcadores , Exposição Ambiental/análise , Saúde Ambiental , Monitoramento Ambiental , Humanos , Bifenilos Policlorados/análise
5.
Tijdschr Psychiatr ; 64(3): 160-165, 2022.
Artigo em Holandês | MEDLINE | ID: mdl-35420145

RESUMO

BACKGROUND: The care for people with trauma- and stressor-related disorders is multidisciplinary. The place of chaplaincy care in multidisciplinary trauma care has received limited attention. AIM: Exploration of the place of chaplaincy care in relation to psychotrauma, moral injury, grief and palliative care and in time in relation to exposure to psychotrauma as a basis for a model of multidisciplinary collaboration. METHOD: Inventory and discussion of the position of chaplaincy care in the literature and guidelines for trauma- and stressor-related disorders. RESULTS: Chaplaincy care may support finding meaning and reconnection in people at risk of trauma and PTSD, moral injury, and traumatic grief. Chaplaincy care is increasingly available for palliative and multicultural care recipients. Most guidelines for trauma care recommend the availability of chaplaincy care or research into the effectiveness of complementary existential, spiritual or meaning-making interventions. CONCLUSION: Traumatic stressors represent limit experiences, whereby the quest for meaning, existential and moral orientation are pre-eminently at stake. The use of chaplaincy care supports finding meaning and reconnection and may thereby potentially contribute to the prevention of traumatic exposure to stressors, persistent symptoms after exposure, and worsening of chronic trauma- and stressor related symptoms.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Pesar , Humanos , Princípios Morais , Transtornos de Estresse Pós-Traumáticos/terapia
6.
Eur J Clin Pharmacol ; 77(8): 1181-1192, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33575848

RESUMO

PURPOSE: The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary. METHODS: Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV). RESULTS: The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441-447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine Cmax correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV. CONCLUSION: The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.


Assuntos
Ketamina/análogos & derivados , Ketamina/farmacocinética , Modelos Biológicos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
8.
Biomed Pharmacother ; 130: 110545, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32731134

RESUMO

There is an urgent need for the introduction of novel and better (i.e., improved risk-benefit profile) compounds for the treatment of major psychiatric disorders, in particular mood and psychotic disorders. However, despite increased societal awareness and a rising public and professional demand for such agents from patients and physicians, the pharmaceutical industry continues to close down its psychopharmacology research facilities in reaction to the lack of success with the search for new psychotropics. It is high time to stop this untoward trend and explore "new" lines of investigation to solve the current crisis in psychopharmacological research. In line with the prevailing molecular view in drug research in general, also in psychopharmacology mechanistic explanations for drug effects are "traditionally" looked for at the level of molecular targets, like receptors and transporters. Also, more recent approaches, although using so-called systems- and function-based approaches to model the multidimensional characteristics of psychiatric disorders and psychotropic drug action, still emphasize this search strategy for new therapeutic leads by identification of single molecules or molecular pathways. This "psychomolecular gaze" overlooks and disregards the fact that psychotropic agents usually are highly hydrophobic and amphipathic/amphiphilic agents that, in addition to their interaction with membrane-bound proteins in the form of e.g. receptors or transporters, also interact strongly with the lipid component of cellular membranes. Here we suggest to develop a program of systematic, whole-cell level based, investigation into the role of these physical-chemical cellular membrane interactions in the therapeutic action of known psychotherapeutics. This complementary yet conceptually different approach, in our opinion, will complement drug development in psychopharmacology and thereby assist in overcoming the current crisis. In this way the "old" physical theory of drug action, which antedates the current, primary molecular, paradigm may offer "new" options for lead discovery in psychopharmacological research.


Assuntos
Membrana Celular/efeitos dos fármacos , Psicofarmacologia/tendências , Psicotrópicos/farmacologia , Psicotrópicos/uso terapêutico , Pesquisa/tendências , Animais , Humanos , Transtornos Mentais/tratamento farmacológico
10.
Food Chem ; 255: 348-356, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29571486

RESUMO

Caramel colours are used by the food industry in a wide range of foods and beverages. During their manufacturing, low molecular weight compounds such as 4-methylimidazole (4-MEI), the structural isomer of 4-MEI, 2-methylimidazole (2-MEI) and 2-acetyl-4-tetrahydroxy-butylimidazole (THI) are generated. The presence of these inevitable by-products of caramel manufacturing can be hazardous to human health. This publication describes an isotope dilution Ultra-High-performance Liquid Chromatography tandem mass spectrometric method (UHPLC-MS/MS) that was developed and validated for the simultaneous quantification of these impurities in both beverages/liquids and foods. A limit of quantification of 5 µg/kg was obtained for 4-MEI and THI. The expanded measurement uncertainty (U; k = 2) for these compounds was below 51% in beverages/liquids and below 56% in foods. As higher measurement uncertainties were obtained for 2-MEI, the developed analytical procedure can only be used in a semi-quantitative way for this compound.


Assuntos
Bebidas/análise , Carboidratos/análise , Análise de Alimentos/métodos , Alimentos , Imidazóis/análise , Cromatografia Líquida , Isótopos/análise , Espectrometria de Massas em Tandem
11.
Food Chem ; 255: 372-379, 2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-29571489

RESUMO

In Europe, 2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) and 4-methylimidazole (4-MEI) are - to a certain level - allowed to be present in the food colours ammonia caramel (E 150c) and sulphite ammonia caramel (E 150d). Besides their presence in food colours, exposure to these contaminants may also include other dietary sources. This study describes the occurrence of THI and 4-MEI in a wide variety of food products (n = 522) purchased from the Belgian market and their dietary intake in Belgian consumers from 15 years old onwards. THI was found to be present in 22.4% of the investigated foods at a level up to 551 µg/kg. For 4-MEI (57.7% quantifiable), concentrations up to 2,835 µg/kg were observed. The average dietary intake amounted to 0.02-0.36 µg kg-1 bw-1 day for THI and 0.4-3.7 µg kg-1 bw-1 day for 4-MEI. Coffee, cola and beer were contributing most to the dietary THI and 4-MEI intake in Belgium.


Assuntos
Bebidas/análise , Carboidratos/análise , Análise de Alimentos/métodos , Alimentos , Imidazóis/análise , Cerveja/análise , Bélgica , Café/química , Ingestão de Alimentos
12.
Environ Pollut ; 232: 105-112, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28931465

RESUMO

Genetic and epigenetic changes were investigated in chronically irradiated Scots pine (Pinus sylvestris L.) populations from territories that were heavily contaminated by radionuclides as result of the Chernobyl Nuclear Power Plant accident. In comparison to the reference site, the genetic diversity revealed by electrophoretic mobility of AFLPs was found to be significantly higher at the radioactively contaminated areas. In addition, the genome of pine trees was significantly hypermethylated at 4 of the 7 affected sites.


Assuntos
Acidente Nuclear de Chernobyl , Variação Genética/efeitos da radiação , Pinus sylvestris/efeitos da radiação , Exposição à Radiação/análise , Monitoramento de Radiação , Metilação de DNA , Pinus
13.
Public Health Action ; 7(Suppl 1): S70-S75, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28744442

RESUMO

Setting: Health facilities providing human immunodeficiency virus (HIV) testing, care and treatment in Liberia. Objective: To evaluate individuals aged ⩾15 years who were tested, diagnosed and enrolled into HIV care before (2013), during (2014) and after the Ebola outbreak (2015). Design: A cross-sectional descriptive study. Results: A median of 6930 individuals aged ⩾15 years per county were tested for HIV before the Ebola outbreak; this number declined by 35% (2444/6930) during the outbreak. HIV positivity remained similar before (7028/207 314, 3.4%) and during the outbreak (4146/121 592, 3.5%). During Ebola, HIV testing declined more in highly affected counties (68 035/127 468, 47%) than in counties that were less affected (16 444/23 955, 31%, P < 0.001). Compared to the pre-Ebola period, HIV testing in less-affected counties recovered more quickly during the post-outbreak period, with a 19% increase in testing, while medium and highly affected counties remained at respectively 38% and 48% below pre-outbreak levels. Enrolment for HIV care increased during and after the outbreak compared to the pre-Ebola period. Conclusion: HIV testing and diagnosis were significantly limited during the Ebola outbreak, with the most severe effects occurring in highly affected counties. However, enrolment for HIV care and treatment were resilient throughout the outbreak. Pro-active measures are needed to sustain HIV testing rates in future epidemics.


Contexte : Structures de santé offrant des tests et une prise en charge de l'infection par le virus de l'immunodéficience humaine (VIH) au Liberia.Objectif : Evaluer les personnes âgées de ⩾15 ans qui sont testées, diagnostiquées et enrôlées dans la prise en charge du VIH avant (2013), pendant (2014) et après la flambée d'Ebola (2015).Schéma : Étude descriptive transversale.Résultats : Une médiane de 6930 personnes âgées de ⩾15 ans par comté ont eu un test VIH avant la flambée d' Ebola ; ce nombre a décliné de 35% (2444/6930) pendant la flambée. La positivité du VIH est restée similaire avant (7028/207 314 ; 3,4%) et pendant la flambée d'Ebola (4146/121 592 ; 3,5%). Pendant Ebola, les tests VIH ont diminué davantage dans les comtés les plus affectés (68 035/127 468 ; 47%) comparés aux comtés moins affectés (16 444/23 955 ; 31% ; P < 0,001). Comparés à la période pré Ebola, les tests VIH dans les comtés les moins affectés ont récupéré plus rapidement pendant la période post flambée, avec une augmentation de 19% des tests, tandis que les comtés moyennement ou très affectés sont restés à 38% et à 48%, respectivement, sous les niveaux d'avant la flambée. L'enrôlement dans la prise en charge du VIH a augmenté pendant et après la flambée par rapport à la période pré Ebola.Conclusion : Le test et le diagnostic du VIH ont été significativement limités pendant la flambée d'Ebola, avec l'impact le plus grave dans les comtés les plus affectés. L'enrôlement dans la prise en charge du VIH a toutefois été résilient tout au long de la flambée. Des mesures proactives sont requises pour maintenir le taux des tests VIH lors de futures épidémies.


Marco de referencia: Los establecimientos de salud que prestan servicios de diagnóstico, atención y tratamiento de la infección por el virus de la inmunodeficiencia humana (VIH) en Liberia.Objetivo: Evaluar el número de personas de edad de ⩾15 años en quienes se practicó la prueba del VIH, se estableció el diagnóstico de infección por el virus y se inscribieron en el servicio de atención antes la epidemia de fiebre hemorrágica del Ébola (2013), durante el brote (2014) y después del mismo (2015).Método: Fue este un estudio transversal descriptivo.Resultados: La mediana del número de personas de edad de ⩾15 años en quienes se practicó la prueba del VIH antes del brote del Ébola por condado fue 6930; esta cifra disminuyó un 35% (2444/6930) durante el brote. La proporción de resultados positivos de la prueba permaneció estable antes del brote epidémico (7028/207 314 ; 3,4%) y durante el mismo (4146/121 592 ; 3,5%). Durante la epidemia del Ébola, la práctica de la prueba del VIH disminuyó más en los condados más afectados (68 035/127 468; −47%) que en los condados con una epidemia de menor nivel (16 444/23 955; −31%; P < 0,001). En comparación con el período pre-Ébola, la recuperación de la práctica de la prueba del VIH después de la epidemia en los condados menos afectados fue más rápida, con un aumento del 19%, pero en los condados donde la epidemia alcanzó un nivel intermedio o alto, las cifras permanecieron un 38% y un 48% inferiores al período pre-Ébola, respectivamente. La inscripción al programa de atención de la infección por el VIH aumentó durante el brote y después del mismo, en comparación con el período pre-Ébola.Conclusión: Los resultados del presente estudio revelan que las pruebas y el diagnóstico de la infección por el VIH se redujeron de manera notable durante el brote epidémico del Ébola y los efectos fueron más acentuados en los condados donde la epidemia alcanzó un alto nivel. Sin embargo, la inscripción al programa de atención y tratamiento resistió durante toda la epidemia. Se precisan medidas anticipatorias que favorezcan la estabilidad de la práctica de la prueba diagnóstica del VIH durante las epidemias futuras.

14.
Eur J Clin Nutr ; 71(8): 995-1001, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28378853

RESUMO

BACKGROUND/OBJECTIVES: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. SUBJECTS/METHODS: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses. RESULTS: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. CONCLUSIONS: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.


Assuntos
Fígado Gorduroso Alcoólico/sangue , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Estudos de Coortes , Biologia Computacional , Estudos Transversais , Dipeptídeos/sangue , Sistemas Inteligentes , Fígado Gorduroso Alcoólico/diagnóstico por imagem , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/fisiopatologia , Feminino , Ácido Glutâmico/análogos & derivados , Ácido Glutâmico/sangue , Humanos , Fígado/diagnóstico por imagem , Fígado/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/metabolismo , Autorrelato , Índice de Gravidade de Doença
15.
Ned Tijdschr Geneeskd ; 160: D89, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27507414

RESUMO

This clinical case presentation describes the disease trajectory in two patients who presented with psychiatric symptoms as a result of abnormal serum glucocorticoid levels. One case involves a 58-year-old man with hypercortisolism, the other case concerns a 55-year-old woman with hypocortisolism. In both cases there was a considerable diagnostic delay in recognizing the underlying adrenal gland pathology. Abnormal glucocorticoid levels, caused by endocrine disorders, often results in psychiatric symptoms. Delay in diagnosis may have adverse consequences. Hyper- or hypocortisolism should be considered in patients who present with an atypical presentation of psychiatric symptoms. Moreover, the absence of specific physical signs or symptoms at first presentation in such patients does not exclude an underlying endocrinological cause. Therefore, physical and psychiatric reassessment of such patients should be considered at regular intervals.


Assuntos
Glucocorticoides/sangue , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Transtornos Mentais/terapia , Pessoa de Meia-Idade
16.
Transpl Infect Dis ; 17(2): 289-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25661804

RESUMO

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms.


Assuntos
Infecções por Acinetobacter , Diabetes Mellitus Tipo 1/cirurgia , Endocardite Bacteriana , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Pâncreas , Complicações Pós-Operatórias , Acinetobacter baumannii/genética , Bacteriemia , Proteínas de Bactérias/genética , Carbapenêmicos , Farmacorresistência Bacteriana/genética , Humanos , Masculino , Pessoa de Meia-Idade , beta-Lactamases/genética
17.
Theor Popul Biol ; 100C: 39-55, 2015 03.
Artigo em Inglês | MEDLINE | ID: mdl-25543095

RESUMO

Rare long distance dispersal events are thought to have a disproportionate impact on the spread of invasive species. Modelling using integrodifference equations suggests that, when long distance contacts are represented by a fat-tailed dispersal kernel, an accelerating wave of advance can ensue. Invasions spreading in this manner could have particularly dramatic effects. Recently, various authors have suggested that demographic stochasticity disrupts wave acceleration. Integrodifference models have been widely used in movement ecology, and as such a clearer understanding of stochastic effects is needed. Here, we present a stochastic non-linear one-dimensional lattice model in which demographic stochasticity and the dispersal regime can be systematically varied. Extensive simulations show that stochasticity has a profound effect on model behaviour, and usually breaks acceleration for fat-tailed kernels. Exceptions are seen for some power law kernels, K(l)∝|l|-ß with ß<3, for which acceleration persists despite stochasticity. Such kernels lack a second moment and are important in 'accelerating' phenomena such as Lévy flights. Furthermore, for long-range kernels the approach to the continuum limit behaviour as stochasticity is reduced is generally slow. Given that real-world populations are finite, stochastic models may give better predictive power when long-range dispersal is important. Insights from mean-field models such as integrodifference equations should be applied with caution in such circumstances.

18.
Artigo em Inglês | MEDLINE | ID: mdl-25375542

RESUMO

Moran processes are often used to model selection in evolutionary simulations. The updating rule in Moran processes is a birth-death process, i. e., selection according to fitness of an individual to give birth, followed by the death of a random individual. For well-mixed populations with only two strategies this updating rule is known to be equivalent to selecting unfit individuals for death and then selecting randomly for procreation (biased death-birth process). It is, however, known that this equivalence does not hold when considering structured populations. Here we study whether changing the updating rule can also have an effect in well-mixed populations in the presence of more than two strategies and high mutation rates. We find, using three models from different areas of evolutionary simulation, that the choice of updating rule can change model results. We show, e. g., that going from the birth-death process to the death-birth process can change a public goods game with punishment from containing mostly defectors to having a majority of cooperative strategies. From the examples given we derive guidelines indicating when the choice of the updating rule can be expected to have an impact on the results of the model.


Assuntos
Teoria dos Jogos , Modelos Biológicos , Taxa de Mutação , Coeficiente de Natalidade , Simulação por Computador , Comportamento Cooperativo , Cadeias de Markov , Mortalidade
19.
Artigo em Inglês | MEDLINE | ID: mdl-25293886

RESUMO

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.


Assuntos
Biomarcadores/análise , Doença Crônica/epidemiologia , Estudos de Coortes , Vigilância da População/métodos , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Manejo de Espécimes/estatística & dados numéricos , Manejo de Espécimes/normas , Adulto , Idoso , Doença Crônica/prevenção & controle , Estudos de Viabilidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Eur J Clin Nutr ; 68(3): 324-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24398637

RESUMO

BACKGROUND/OBJECTIVES: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. SUBJECTS/METHODS: Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. RESULTS: In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. CONCLUSIONS: The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.


Assuntos
Registros de Dieta , Avaliação Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Internet , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
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