Evaluation of community-wide interventions: The ecologic case-referent study design

In a setting of long-standing, community-wide and generally accepted prevention activities like youth health care services in The Netherlands, evaluative research in the form of experimental studies is hardly possible. Furthermore, as most interventions will bear fruit only after several years and the effects are often described in rather vague terms, even nonexperimental study designs are fraught with possible difficulties. Although a study design using aggregate data is generally considered inferior or 'incomplete', in many cases, especially in health services research, this approach can be the only one feasible to evaluate the effectiveness of preventive programmes and interventions. In this article we present the ecologic case-referent design as a potentially expedient and valid method for estimating the ecologic effect of a population-wide intervention on the outcome rate in those populations. In this case-referent design, many variables are measured at the individual level, whereas the main exposure variable is measured at an aggregate or ecologic level. Using recently published studies as an example, the advantages and drawbacks of the design are discussed using the randomised controlled trial design as the referent study design

Paintable Encapsulated Body-Temperature-Responsive Photonic Reflectors with Arbitrary Shapes

A temperature-responsive photonic coating on a flexible substrate was prepared by a photoinduced phase-separation process. In this coating a low molecular weight cholesteric liquid crystal (Ch-LC) mixture was encapsulated between the substrate and an in situ formed protective polymer top layer. The photonic coating showed a blue-shift of the photonic reflection band of 100 nm by heating from 22 to 23 °C due to the close proximity to the smectic to cholesteric phase transition and an overall 330 nm blue-shift while heating from 22 to 45 °C. Hence, the red coating turned green upon contact with skin within seconds. Furthermore, the coating structure and composition were investigated in detail, revealing a thick top coat. The adhesion of the coating was improved by providing trays on the substrate (by etching or 3D printing), resulting in a link between arbitrary-shaped substrates and the protective polymer top layer. These bendable coatings could be of interest for sensors, anticounterfeit labels, or customizable aesthetic applications.</p

Athymic nude rat. III natural cell mediated cytotoxicity.

Homozygous rnu/rnu and heterozygous +/rnu rats were investigated and compared with each other for the existence of natural cell-mediated cytotoxicity. Investigated were total, adherent, and nonadherent cell populations from spleen, peritoneal cavity, and mesenteric lymph node. The natural killer (NK) cell activity was measured in a 4-hr 51Cr-release assay with a xenogeneic murine YAC lymphoma target cell line. In both and +/rnu rats the peritoneal cavity had the highest percentage of activity, while the spleen and mesenteric lymph node showed a lower activity. The mesenteric lymph node of +/rnu rats of 8–10 weeks of age was found to express a very low activity, in contrast to a very high activity in rats. For almost every effector to target cell (E:T) ratio investigated (100, 70, 50, and 10), the natural killer cell activity in the nude rats was found to be significantly higher than in their thymus-bearing littermates. In comparison with that of +/rnu rats, NK activity in the nonadherent cell fractions of athymic rats was 50 to 60% higher in spleen cells, doubled in peritoneal cells, and increased 10-fold or higher in lymph node cells. Investigations o

Using schema transformation pathways for data lineage tracing

With the increasing amount and diversity of information available on the Internet, there has been a huge growth in information systems that need to integrate data from distributed, heterogeneous data sources. Tracing the lineage of the integrated data is one of the problems being addressed in data warehousing research. This paper presents a data lineage tracing approach based on schema transformation pathways. Our approach is not limited to one specific data model or query language, and would be useful in any data transformation/integration framework based on sequences of primitive schema transformations

Antigenic and genetic variability of human metapneumoviruses

Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences

Effects of epidemic threshold definition on disease spread statistics

We study the statistical properties of the SIR epidemics in heterogeneous networks, when an epidemic is defined as only those SIR propagations that reach or exceed a minimum size s_c. Using percolation theory to calculate the average fractional size of an epidemic, we find that the strength of the spanning link percolation cluster $P_{\infty}$ is an upper bound to . For small values of s_c, $P_{\infty}$ is no longer a good approximation, and the average fractional size has to be computed directly. The value of s_c for which $P_{\infty}$ is a good approximation is found to depend on the transmissibility T of the SIR. We also study Q, the probability that an SIR propagation reaches the epidemic mass s_c, and find that it is well characterized by percolation theory. We apply our results to real networks (DIMES and Tracerouter) to measure the consequences of the choice s_c on predictions of average outcome sizes of computer failure epidemics.Comment: 12 pages, 8 figure

Sub-terahertz, microwaves and high energy emissions during the December 6, 2006 flare, at 18:40 UT

The presence of a solar burst spectral component with flux density increasing with frequency in the sub-terahertz range, spectrally separated from the well-known microwave spectral component, bring new possibilities to explore the flaring physical processes, both observational and theoretical. The solar event of 6 December 2006, starting at about 18:30 UT, exhibited a particularly well-defined double spectral structure, with the sub-THz spectral component detected at 212 and 405 GHz by SST and microwaves (1-18 GHz) observed by the Owens Valley Solar Array (OVSA). Emissions obtained by instruments in satellites are discussed with emphasis to ultra-violet (UV) obtained by the Transition Region And Coronal Explorer (TRACE), soft X-rays from the Geostationary Operational Environmental Satellites (GOES) and X- and gamma-rays from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The sub-THz impulsive component had its closer temporal counterpart only in the higher energy X- and gamma-rays ranges. The spatial positions of the centers of emission at 212 GHz for the first flux enhancement were clearly displaced by more than one arc-minute from positions at the following phases. The observed sub-THz fluxes and burst source plasma parameters were found difficult to be reconciled to a purely thermal emission component. We discuss possible mechanisms to explain the double spectral components at microwaves and in the THz ranges.Comment: Accepted version for publication in Solar Physic

Qualitative grading of aortic regurgitation: a pilot study comparing CMR 4D flow and echocardiography

Over the past 10 years there has been intense research in the development of volumetric visualization of intracardiac flow by cardiac magnetic resonance (CMR). This volumetric time resolved technique called CMR 4D flow imaging has several advantages over standard CMR. It offers anatomical, functional and flow information in a single free-breathing, ten-minute acquisition. However, the data obtained is large and its processing requires dedicated software. We evaluated a cloud-based application package that combines volumetric data correction and visualization of CMR 4D flow data, and assessed its accuracy for the detection and grading of aortic valve regurgitation using transthoracic echocardiography as reference. Between June 2014 and January 2015, patients planned for clinical CMR were consecutively approached to undergo the supplementary CMR 4D flow acquisition. Fifty four patients (median age 39 years, 32 males) were included. Detection and grading of the aortic valve regurgitation using CMR 4D flow imaging were evaluated against transthoracic echocardiography. The agreement between 4D flow CMR and transthoracic echocardiography for grading of aortic valve regurgitation was good (κ = 0.73). To identify relevant, more than mild aortic valve regurgitation, CMR 4D flow imaging had a sensitivity of 100 % and specificity of 98 %. Aortic regurgitation can be well visualized, in a similar manner as transthoracic echocardiography, when using CMR 4D flow imaging

Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant

Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events

A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors

__Background:__ Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients' plasma. __Methods:__ A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample. __Results:__ The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patien