Soft x ray spectroscopy of coronene and coronene H cations The influence of hydrogenation on electronic structure and photofragmentation

We have studied soft x ray absorption in coronene and in singly hydrogenated coronene cations. Hydrogenation on the one hand closes the singly occupied molecular orbital of the coronene radical cation and thus decreases the reactivity of the molecule. On the other hand, the additional H atom breaks the coronene D6h symmetry and exhibits a comparably small binding energy. The effect of single hydrogenation on soft x ray photoionization is therefore hard to predict. In our experiments, the mass selected polycyclic aromatic hydrocarbons cations were stored in a cryogenic radio frequency ion trap and exposed to monochromatic x rays with energies around the carbon K edge. The partial photoion yields were recorded as a function of photon energy by means of time of flight mass spectrometry. The experimental data was compared to time dependent density functional theory calculations based on a short range corrected functional. The combination of experiment and theory allowed for precise assignment of 1s excitations to the resonances in the spectra. We found that these resonant transitions as well as direct 1s ionization into the continuum could induce nondissociative ionization, H H2 loss, as well as fragmentation of the carbon backbone. For multiple ionization, neutral hydrogen loss was found to compete with fission reactions where H or H2 is released. H attachment was found to substantially decrease backbone fragmentatio

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio = 0.54, 95% confidence interval = 0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring. Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective. Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs. Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds. Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective

Alteração de atributos químicos do solo e estado nutricional e características agronômicas de plantas de milho, considerando as modalidades de calagem em plantio direto

A aplicação de calcário na superfície do solo em sistema plantio direto, sem incorporação, em determinadas condições edafoclimáticas, não tem sido eficaz na correção da acidez e no fornecimento de cálcio e magnésio às plantas. Na busca de alternativas para a realização da calagem sem as operações convencionais de aração e gradagem, o trabalho teve como objetivo avaliar a eficiência de diferentes modalidades de calagem nos atributos químicos do solo, no estado nutricional e nas características agronômicas da cultura do milho. O delineamento experimental utilizado foi o de blocos ao acaso, em parcelas subdivididas, com três repetições. Os tratamentos aplicados nas parcelas foram: milho híbrido duplo Z 8447, variedade de milho AL 25 e híbrido duplo AG 122 e, nas subparcelas, testemunha sem calagem, calcário aplicado ao longo do perfil do solo no sulco de semeadura, calcário aplicado a lanço na superfície do solo e calcário aplicado ao longo do perfil do solo no sulco de semeadura, mais calcário aplicado a lanço na superfície. Nos tratamentos que receberam calcário no sulco, a semeadura foi realizada no mesmo sulco que recebeu o calcário. A amostragem do solo foi feita 30 e 150 dias após a calagem, a partir da linha de semeadura até 25 cm de distância desta, em cinco profundidades. Determinaram-se pH em água e Ca, Mg e Al trocáveis nas amostras. Avaliou-se o estado nutricional do tecido foliar dos três cultivares, bem como algumas características agronômicas da cultura. Os resultados indicaram que o calcário aplicado no sulco de semadura foi distribuído eficientemente ao longo do perfil do solo até 20 cm de profundidade, em uma faixa de 10 cm de largura. O calcário aplicado na superfície teve efeito sobre as características químicas do solo somente até 5 cm de profundidade. A aplicação conjunta de calcário ao longo do perfil do solo no sulco de semeadura mais calcário em superfície foi mais eficiente para elevar os valores de pH e os teores Ca e Mg trocáveis e diminuir os teores de Al trocável. O estado nutricional dos cultivares e as características agronômicas do milho não foram afetados pelos tratamentos

Tumour necrosis factor - alpha mediated mechanisms of cognitive dysfunction

Background: Tumour necrosis factor - alpha (TNF-α) is a pro-inflammatory cytokine that combines a plethora of activities in the early stages of an immune response. TNF-α has gained increasing importance given TNF-α upregulation in multiple brain pathologies like neuropsychiatric conditions such as depression, schizophrenia, as well as neuroinflammatory disorder like multiple sclerosis (MS).\ud \ud Aim: The aim of this review is to critically analyse neurobiological, immunological and molecular mechanisms through which TNF-α influences the development of cognitive dysfunction.\ud \ud Principal findings/results: The review presents several lines of original research showing that the immunological properties of TNF-α exacerbate inflammatory responses in the central nervous system such as microglial and endothelial activation, lymphocytic and monocytic infiltration and the expression of downstream pro-inflammatory cytokines and apoptotic factors. Depression, schizophrenia, and MS all manifest symptoms of activated immune response along with cognitive dysfunction, with TNF-α overexpression as a central clinical feature common to these disorders. Furthermore, TNF-α acts negatively on neuroplasticity and the molecular mechanisms of memory and learning (i.e., long-term potentiation and long-term depression). TNF-α also exerts influence over the production of neurotrophins (i.e., nerve growth factor and brain-derived neurotrophic factor), neurogenesis, and dendritic branching.\ud \ud Conclusions/significance: This review outlines that TNF-α and its receptors have a substantial yet underappreciated influence on the development and progression of neuropsychiatric symptoms across several disease entities. An improved understanding of these underlying mechanisms may help develop novel therapeutic targets in the form of drugs specifically targeting downstream products of TNF-α activation within the central nervous system