High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult

Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS

The AMADEUS system is an integral part of the ANTARES neutrino telescope in the Mediterranean Sea. The project aims at the investigation of techniques for acoustic neutrino detection in the deep sea. Installed at a depth of more than 2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for the broad-band recording of signals with frequencies ranging up to 125kHz. AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each one holding six acoustic sensors that are arranged at distances of roughly 1m from each other. The clusters are installed with inter-spacings ranging from 15m to 340m. Acoustic data are continuously acquired and processed at a computer cluster where online filter algorithms are applied to select a high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in 2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like signals in the deep sea, the characteristics of ambient noise and transient signals have been investigated. In this article, the AMADEUS system will be described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

The ANTARES Telescope Neutrino Alert System

The ANTARES telescope has the capability to detect neutrinos produced in astrophysical transient sources. Potential sources include gamma-ray bursts, core collapse supernovae, and flaring active galactic nuclei. To enhance the sensitivity of ANTARES to such sources, a new detection method based on coincident observations of neutrinos and optical signals has been developed. A fast online muon track reconstruction is used to trigger a network of small automatic optical telescopes. Such alerts are generated for special events, such as two or more neutrinos, coincident in time and direction, or single neutrinos of very high energy.Comment: 17 pages, 9 figures submitted to Astroparticle Physic

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey

Background: 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. Methods: Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI &apos;D&apos;, generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer&apos;s Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. Results: Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. Conclusion: Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.Clinical NeurologySCI(E)SSCI17ARTICLEnull

Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope

The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total live time of 863 days, are used to measure the oscillation parameters of atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20 GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon neutrinos of such energies crossing the Earth. The parameters determining the oscillation of atmospheric neutrinos are extracted by fitting the event rate as a function of the ratio of the estimated neutrino energy and reconstructed flight path through the Earth. Measurement contours of the oscillation parameters in a two-flavour approximation are derived. Assuming maximum mixing, a mass difference of $\Delta m_{32}^2=(3.1\pm 0.9)\cdot 10^{-3}$ eV$^2$ is obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure

Small-scale, homelike facilities versus regular psychogeriatric nursing home wards: a cross-sectional study into residents' characteristics

<p>Abstract</p> <p>Background</p> <p>Nursing home care for people with dementia is increasingly organized in small-scale and homelike care settings, in which normal daily life is emphasized. Despite this increase, relatively little is known about residents' characteristics and whether these differ from residents in traditional nursing homes. This study explored and compared characteristics of residents with dementia living in small-scale, homelike facilities and regular psychogeriatric wards in nursing homes, focusing on functional status and cognition.</p> <p>Methods</p> <p>A cross-sectional study was conducted, including 769 residents with dementia requiring an intensive level of nursing home care: 586 from regular psychogeriatric wards and 183 residents from small-scale living facilities. Functional status and cognition were assessed using two subscales from the Resident Assessment Instrument Minimum Data Set (RAI-MDS): the Activities of Daily Living-Hierarchy scale (ADL-H) and the Cognitive Performance Scale (CPS). In addition, care dependency was measured using Dutch Care Severity Packages (DCSP). Finally, gender, age, living condition prior to admission and length of stay were recorded. Descriptive analyses, including independent samples t- tests and chi-square tests, were used. To analyze data in more detail, multivariate logistic regression analyses were performed.</p> <p>Results</p> <p>Residents living in small-scale, homelike facilities had a significantly higher functional status and cognitive performance compared with residents in regular psychogeriatric wards. In addition, they had a shorter length of stay, were less frequently admitted from home and were more often female than residents in regular wards. No differences were found in age and care dependency. While controlling for demographic variables, the association between dementia care setting and functional status and cognition remained.</p> <p>Conclusions</p> <p>Although residents require a similar intensive level of nursing home care, their characteristics differ among small-scale living facilities and regular psychogeriatric wards. These differences may limit research into effects and feasibility of various types of dementia care settings. Therefore, these studies should take resident characteristics into account in their design, for example by using a matching procedure.</p

SOD1 and Amyotrophic Lateral Sclerosis: Mutations and Oligomerization

There are about 100 single point mutations of copper, zinc superoxide dismutase 1 (SOD1) which are reported (http://alsod.iop.kcl.ac.uk/Als/index.aspx) to be related to the familial form (fALS) of amyotrophic lateral sclerosis (ALS). These mutations are spread all over the protein. It is well documented that fALS produces protein aggregates in the motor neurons of fALS patients, which have been found to be associated to mitochondria. We selected eleven SOD1 mutants, most of them reported as pathological, and characterized them investigating their propensity to aggregation using different techniques, from circular dichroism spectra to ThT-binding fluorescence, size-exclusion chromatography and light scattering spectroscopy. We show here that these eleven SOD1 mutants, only when they are in the metal-free form, undergo the same general mechanism of oligomerization as found for the WT metal-free protein. The rates of oligomerization are different but eventually they give rise to the same type of soluble oligomeric species. These oligomers are formed through oxidation of the two free cysteines of SOD1 (6 and 111) and stabilized by hydrogen bonds, between beta strands, thus forming amyloid-like structures. SOD1 enters the mitochondria as demetallated and mitochondria are loci where oxidative stress may easily occur. The soluble oligomeric species, formed by the apo form of both WT SOD1 and its mutants through an oxidative process, might represent the precursor toxic species, whose existence would also suggest a common mechanism for ALS and fALS. The mechanism here proposed for SOD1 mutant oligomerization is absolutely general and it provides a common unique picture for the behaviors of the many SOD1 mutants, of different nature and distributed all over the protein