Antimargination of microparticles and platelets in the vicinity of branching vessels

We investigate the margination of microparticles/platelets in blood flow through complex geometries typical for in vivo vessel networks: a vessel confluence and a bifurcation. Using 3D Lattice-Boltzmann simulations, we confirm that behind the confluence of two vessels a cell-free layer devoid of red blood cells develops in the channel center. Despite its small size of roughly one micrometer, this central cell-free layer persists for up to 100 $\mu$m after the confluence. Most importantly, we show from simulations that this layer also contains a significant amount of microparticles/platelets and validate this result by in vivo microscopy in mouce venules. At bifurcations, however, a similar effect does not appear and margination is largely unaffected by the geometry. This anti-margination towards the vessel center after a confluence may explain in vivo observations by Woldhuis et al. [Am. J. Physiol. 262, H1217 (1992)] where platelet concentrations near the vessel wall are seen to be much higher on the arteriolar side (containing bifurcations) than on the venular side (containing confluences) of the vascular system

Changes in Blood Cell Deformability in Chorea-Acanthocytosis and Effects of Treatment With Dasatinib or Lithium

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investigated blood cell deformability of five ChAc patients compared to healthy controls during up to 1-year individual off-label treatment with the tyrosine kinase inhibitor dasatinib or several weeks with lithium. Measurements with two microfluidic techniques allowed us to assess RBC deformability under different shear stresses. Furthermore, we characterized leukocyte stiffness at high shear stresses. The results showed that blood cell deformability–including both RBCs and leukocytes - in general was altered in ChAc patients compared to healthy donors. Therefore, this study shows for the first time an impairment of leukocyte properties in ChAc. During treatment with dasatinib or lithium, we observed alterations in RBC deformability and a stiffness increase for leukocytes. The hematological phenotype of ChAc patients hinted at a reorganization of the cytoskeleton in blood cells which partly explains the altered mechanical properties observed here. These findings highlight the need for a systematic assessment of the contribution of impaired blood cell mechanics to the clinical manifestation of ChAc

Conceptualising the technical relationship of animal disease surveillance to intervention and mitigation as a basis for economic analysis

<p>Abstract</p> <p>Background</p> <p>Surveillance and intervention are resource-using activities of strategies to mitigate the unwanted effects of disease. Resources are scarce, and allocating them to disease mitigation instead of other uses necessarily involves the loss of alternative sources of benefit to people. For society to obtain the maximum benefits from using resources, the gains from disease mitigation must be compared to the resource costs, guiding decisions made with the objective of achieving the optimal net outcome.</p> <p>Discussion</p> <p>Economics provides criteria to guide decisions aimed at optimising the net benefits from the use of scarce resources. Assessing the benefits of disease mitigation is no exception. However, the technical complexity of mitigation means that economic evaluation is not straightforward because of the technical relationship of surveillance to intervention. We argue that analysis of the magnitudes and distribution of benefits and costs for any given strategy, and hence the outcome in net terms, requires that mitigation is considered in three conceptually distinct stages. In Stage I, 'sustainment', the mitigation objective is to sustain a free or acceptable status by preventing an increase of a pathogen or eliminating it when it occurs. The role of surveillance is to document that the pathogen remains below a defined threshold, giving early warning of an increase in incidence or other significant changes in risk, and enabling early response. If a pathogen is not contained, the situation needs to be assessed as Stage II, 'investigation'. Here, surveillance obtains critical epidemiological information to decide on the appropriate intervention strategy to reduce or eradicate a disease in Stage III, 'implementation'. Stage III surveillance informs the choice, timing, and scale of interventions and documents the progress of interventions directed at prevalence reduction in the population.</p> <p>Summary</p> <p>This article originates from a research project to develop a conceptual framework and practical tool for the economic evaluation of surveillance. Exploring the technical relationship between mitigation as a source of economic value and surveillance and intervention as sources of economic cost is crucial. A framework linking the key technical relationships is proposed. Three conceptually distinct stages of mitigation are identified. Avian influenza, salmonella, and foot and mouth disease are presented to illustrate the framework.</p

Characterization of 30 76^{76}Ge enriched Broad Energy Ge detectors for GERDA Phase II

The GERmanium Detector Array (GERDA) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double beta decay of $^{76}$Ge into $^{76}$Se+2e$^-$. GERDA has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new Ge detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the HADES underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for GERDA Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the strength of pulse shape simulation codes.Comment: 29 pages, 18 figure

The first search for bosonic super-WIMPs with masses up to 1 MeV/c2^2 with GERDA

We present the first search for bosonic super-WIMPs as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-beta decay experiment which operates high-purity germanium detectors enriched in $^{76}$Ge in an ultra-low background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c$^2$ to 1 MeV/c$^2$. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c$^2$ have been set. As an example, at a mass of 150 keV/c$^2$ the most stringent direct limits on the dimensionless couplings of axion-like particles and dark photons to electrons of $g_{ae} < 3 \cdot 10^{-12}$ and ${\alpha'}/{\alpha} < 6.5 \cdot 10^{-24}$ at 90% credible interval, respectively, were obtained.Comment: 6 pages, 3 figures, submitted to Physical Review Letters, added list of authors, updated ref. [21

Background free search for neutrinoless double beta decay with GERDA Phase II

The Standard Model of particle physics cannot explain the dominance of matter over anti-matter in our Universe. In many model extensions this is a very natural consequence of neutrinos being their own anti-particles (Majorana particles) which implies that a lepton number violating radioactive decay named neutrinoless double beta ($0\nu\beta\beta$) decay should exist. The detection of this extremely rare hypothetical process requires utmost suppression of any kind of backgrounds. The GERDA collaboration searches for $0\nu\beta\beta$ decay of $^{76}$Ge (^{76}\rm{Ge} \rightarrow\,^{76}\rm{Se} + 2e^-) by operating bare detectors made from germanium with enriched $^{76}$Ge fraction in liquid argon. Here, we report on first data of GERDA Phase II. A background level of $\approx10^{-3}$ cts/(keV$\cdot$kg$\cdot$yr) has been achieved which is the world-best if weighted by the narrow energy-signal region of germanium detectors. Combining Phase I and II data we find no signal and deduce a new lower limit for the half-life of $5.3\cdot10^{25}$ yr at 90 % C.L. Our sensitivity of $4.0\cdot10^{25}$ yr is competitive with the one of experiments with significantly larger isotope mass. GERDA is the first $0\nu\beta\beta$ experiment that will be background-free up to its design exposure. This progress relies on a novel active veto system, the superior germanium detector energy resolution and the improved background recognition of our new detectors. The unique discovery potential of an essentially background-free search for $0\nu\beta\beta$ decay motivates a larger germanium experiment with higher sensitivity.Comment: 14 pages, 9 figures, 1 table; ; data, figures and images available at http://www.mpi-hd.mpg/gerda/publi

The background in the neutrinoless double beta decay experiment GERDA

The GERmanium Detector Array (GERDA) experiment at the Gran Sasso underground laboratory (LNGS) of INFN is searching for neutrinoless double beta decay of 76Ge. The signature of the signal is a monoenergetic peak at 2039 keV, the Q-value of the decay, Q_bb. To avoid bias in the signal search, the present analysis does not consider all those events, that fall in a 40 keV wide region centered around Q_bb. The main parameters needed for the neutrinoless double beta decay analysis are described. A background model was developed to describe the observed energy spectrum. The model contains several contributions, that are expected on the basis of material screening or that are established by the observation of characteristic structures in the energy spectrum. The model predicts a flat energy spectrum for the blinding window around Q_bb with a background index ranging from 17.6 to 23.8*10^{-3} counts/(keV kg yr). A part of the data not considered before has been used to test if the predictions of the background model are consistent. The observed number of events in this energy region is consistent with the background model. The background at Q-bb is dominated by close sources, mainly due to 42K, 214Bi, 228Th, 60Co and alpha emitting isotopes from the 226Ra decay chain. The individual fractions depend on the assumed locations of the contaminants. It is shown, that after removal of the known gamma peaks, the energy spectrum can be fitted in an energy range of 200 kev around Q_bb with a constant background. This gives a background index consistent with the full model and uncertainties of the same size

Limits on uranium and thorium bulk content in GERDA Phase I detectors

Internal contaminations of $^{238}$U, $^{235}$U and $^{232}$Th in the bulk of high purity germanium detectors are potential backgrounds for experiments searching for neutrinoless double beta decay of $^{76}$Ge. The data from GERDA Phase~I have been analyzed for alpha events from the decay chain of these contaminations by looking for full decay chains and for time correlations between successive decays in the same detector. No candidate events for a full chain have been found. Upper limits on the activities in the range of a few nBq/kg for $^{226}$Ra, $^{227}$Ac and $^{228}$Th, the long-lived daughter nuclides of $^{238}$U, $^{235}$U and $^{232}$Th, respectively, have been derived. With these upper limits a background index in the energy region of interest from $^{226}$Ra and $^{228}$Th contamination is estimated which satisfies the prerequisites of a future ton scale germanium double beta decay experiment.Comment: 2 figures, 7 page