Neuroinflammation as common denominator in heart failure associated mental dysfunction:Studies in animal models

Patients with cardiovascular disease have a higher risk to develop mental dysfunction, like depression or memory impairment. To better treat this group of patients we need to better understand the causes of this relationship. Previous studies have indicated that inflammation plays a role in both conditions. In our study we have studied (neuro)inflammation and behavioural changes in animal models of heart attack (myocardial infarction, MI). We specifically looked at microglia and the two inflammatory markers tumour necrosis factor alpha (TNF-α) and neutrophil gelatinase-associated lipocalin (NGAL). Microglia are immune cells in the brain, we know they are involved in conditions such as Alzheimer’s disease and depression. TNF-α is an inflammatory marker that is raised in the blood of patients after MI and also in depression. NGAL is another inflammatory marker that is raised in the blood of patient with heart failure and is associated with symptoms of depression in heart failure patients. In our mouse model of MI we found that TNF-α was raised in the brain after MI, we also found localized activation of microglia. In rats NGAL was raised after MI and NGAL levels were associated with behavioral changes. Microglia activation was also associated with behavioural changes. A final study in a model for abdominal surgery also showed changes in microglia and NGAL, indicating these are not specific for MI, but more likely a general response to physical damage

Space-based passive microwave soil moisture retrievals and the correction for a dynamic open water fraction

The large observation footprint of low-frequency satellite microwave emissions complicates the interpretation of near-surface soil moisture retrievals. While the effect of sub-footprint lateral heterogeneity is relatively limited under unsaturated conditions, open water bodies (if not accounted for) cause a strong positive bias in the satellite-derived soil moisture retrieval. This bias is generally assumed static and associated with large, continental lakes and coastal areas. Temporal changes in the extent of smaller water bodies as small as a few percent of the sensor footprint size, however, can cause significant and dynamic biases. We analysed the influence of such small open water bodies on near-surface soil moisture products derived from actual (non-synthetic) data from the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) for three areas in Oklahoma, USA. Differences between on-ground observations, model estimates and AMSR-E retrievals were related to dynamic estimates of open water fraction, one retrieved from a global daily record based on higher frequency AMSR-E data, a second derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and a third through inversion of the radiative transfer model, used to retrieve soil moisture. The comparison demonstrates the presence of relatively small areas (<0.05) of open water in or near the sensor footprint, possibly in combination with increased, below-critical vegetation density conditions (optical density <0.8), which contribute to seasonally varying biases in excess of 0.2 (m<sup>3</sup> m<sup>−3</sup>) soil water content. These errors need to be addressed, either through elimination or accurate characterisation, if the soil moisture retrievals are to be used effectively in a data assimilation scheme

Vaccination prevented short-term memory loss, but deteriorated long-term spatial memory in Alzheimer's disease mice, independent of amyloid-β pathology

Background: Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer's disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed.Objective: Study the therapeutic potential of this new vaccine in a mouse model for AD.Methods: J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests.Results: J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter.Conclusion: J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.</p

Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2 expression is increased in the periphery and the brain in different age-related CNS diseases and also their risk factor conditions. Experimental studies indicate that Lcn2 contributes to various neuropathophysiological processes of age-related CNS diseases, including exacerbated neuroinflammation, cell death and iron dysregulation, which may negatively impact cognitive function. We hypothesize that increased Lcn2 levels as a result of age-related risk factor conditions may sensitize the brain and increase the risk to develop age-related CNS diseases. In this review we first provide a comprehensive overview of the known functions of Lcn2, and its effects in the CNS. Subsequently, this review explores Lcn2 as a potential (neuro)inflammatory link between different risk factor conditions and the development of age-related CNS disorders. Altogether, evidence convincingly indicates Lcn2 as a key constituent in ageing and age-related brain diseases

The transformation of earth-system observations into information of socio-economic value in GEOSS

The Group on Earth Observations System of Systems, GEOSS, is a co-ordinated initiative by many nations to address the needs for earth-system information expressed by the 2002 World Summit on Sustainable Development. We discuss the role of earth-system modelling and data assimilation in transforming earth-system observations into the predictive and status-assessment products required by GEOSS, across many areas of socio-economic interest. First we review recent gains in the predictive skill of operational global earth-system models, on time-scales of days to several seasons. We then discuss recent work to develop from the global predictions a diverse set of end-user applications which can meet GEOSS requirements for information of socio-economic benefit; examples include forecasts of coastal storm surges, floods in large river basins, seasonal crop yield forecasts and seasonal lead-time alerts for malaria epidemics. We note ongoing efforts to extend operational earth-system modelling and assimilation capabilities to atmospheric composition, in support of improved services for air-quality forecasts and for treaty assessment. We next sketch likely GEOSS observational requirements in the coming decades. In concluding, we reflect on the cost of earth observations relative to the modest cost of transforming the observations into information of socio-economic value

European Gravity Service for Improved Emergency Management - Status and project highlights

European Gravity Service for Improved Emergency Management - Status and project highlight

European Gravity Service for Improved Emergency Management - Status and project highlights

European Gravity Service for Improved Emergency Management - Status and project highlight

De-identifying a public use microdata file from the Canadian national discharge abstract database

<p>Abstract</p> <p>Background</p> <p>The Canadian Institute for Health Information (CIHI) collects hospital discharge abstract data (DAD) from Canadian provinces and territories. There are many demands for the disclosure of this data for research and analysis to inform policy making. To expedite the disclosure of data for some of these purposes, the construction of a DAD public use microdata file (PUMF) was considered. Such purposes include: confirming some published results, providing broader feedback to CIHI to improve data quality, training students and fellows, providing an easily accessible data set for researchers to prepare for analyses on the full DAD data set, and serve as a large health data set for computer scientists and statisticians to evaluate analysis and data mining techniques. The objective of this study was to measure the probability of re-identification for records in a PUMF, and to de-identify a national DAD PUMF consisting of 10% of records.</p> <p>Methods</p> <p>Plausible attacks on a PUMF were evaluated. Based on these attacks, the 2008-2009 national DAD was de-identified. A new algorithm was developed to minimize the amount of suppression while maximizing the precision of the data. The acceptable threshold for the probability of correct re-identification of a record was set at between 0.04 and 0.05. Information loss was measured in terms of the extent of suppression and entropy.</p> <p>Results</p> <p>Two different PUMF files were produced, one with geographic information, and one with no geographic information but more clinical information. At a threshold of 0.05, the maximum proportion of records with the diagnosis code suppressed was 20%, but these suppressions represented only 8-9% of all values in the DAD. Our suppression algorithm has less information loss than a more traditional approach to suppression. Smaller regions, patients with longer stays, and age groups that are infrequently admitted to hospitals tend to be the ones with the highest rates of suppression.</p> <p>Conclusions</p> <p>The strategies we used to maximize data utility and minimize information loss can result in a PUMF that would be useful for the specific purposes noted earlier. However, to create a more detailed file with less information loss suitable for more complex health services research, the risk would need to be mitigated by requiring the data recipient to commit to a data sharing agreement.</p