Land-Applied Goat Manure as a Source of Human QFever in the Netherlands, 2006–2010

Studies have shown a link between Q-fever positive farms (QFPFs) and community cases of human Q-fever. Our study is the first to investigate the potential role of contaminated land-applied manure in human Q-fever, based on a large set of nationwide notification and farm management data. Time between manure application and disease onset in geographically linked notified human cases coincided with the incubation period of Q-fever. Proximity of contaminated land parcels predicted human cases better than proximity of QFPFs (80% vs. 58%, 0–5 km in 2009). Incidence around QFPFs and contaminated land parcels decreased with distance, but not around non-contaminated land parcels. Incidence was higher around contaminated land parcels than non-contaminated land parcels (RR = [10],95%CI = [7], [1]–[14,2]). Our findings deliver evidence that, apart from QFPFs, land-applied contaminated manure may be another source of human Q-fever

Underreporting of meningococcal disease incidence in the Netherlands: results from a capture-recapture analysis based on three registration sources with correction for false positive diagnoses.

In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture-recapture method. Data over 1993-1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture-recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture-recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture-recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs

The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse

The Mouse Genome Database (MGD, http://www.informatics.jax.org) is the international community resource for integrated genetic, genomic and biological data about the laboratory mouse. Data in MGD are obtained through loads from major data providers and experimental consortia, electronic submissions from laboratories and from the biomedical literature. MGD maintains a comprehensive, unified, non-redundant catalog of mouse genome features generated by distilling gene predictions from NCBI, Ensembl and VEGA. MGD serves as the authoritative source for the nomenclature of mouse genes, mutations, alleles and strains. MGD is the primary source for evidence-supported functional annotations for mouse genes and gene products using the Gene Ontology (GO). MGD provides full annotation of phenotypes and human disease associations for mouse models (genotypes) using terms from the Mammalian Phenotype Ontology and disease names from the Online Mendelian Inheritance in Man (OMIM) resource. MGD is freely accessible online through our website, where users can browse and search interactively, access data in bulk using Batch Query or BioMart, download data files or use our web services Application Programming Interface (API). Improvements to MGD include expanded genome feature classifications, inclusion of new mutant allele sets and phenotype associations and extensions of GO to include new relationships and a new stream of annotations via phylogenetic-based approaches

Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings

Characterization of segmental flexibility is needed to understand the biological mechanisms of the very large category of functionally diverse proteins, exemplified by the regulators of complement activation, that consist of numerous compact modules or domains linked by short, potentially flexible, sequences of amino acid residues. The use of NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, to evaluate interdomain motion is established but only for two-domain proteins. We focused on the three N-terminal domains (called CCPs or SCRs) of the important complement regulator, human factor H (i.e. FH1-3). These domains cooperate to facilitate cleavage of the key complement activation-specific protein fragment, C3b, forming iC3b that no longer participates in the complement cascade. We refined a three-dimensional solution structure of recombinant FH1-3 based on nuclear Overhauser effects and RDCs. We then employed a rudimentary series of RDC datasets, collected in media containing magnetically aligned bicelles (disk-like particles formed from phospholipids) under three different conditions, to estimate interdomain motions. This circumvents a requirement of previous approaches for technically difficult collection of five independent RDC datasets. More than 80% of conformers of this predominantly extended three-domain molecule exhibit flexions of < 40 °. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3), could facilitate recognition of C3b via initial anchoring and eventual reorganization of modules to the conformation captured in the previously solved crystal structure of a C3b:FH1-4 complex

Spontaneous clearance of Chlamydia trachomatis accounting for bacterial viability in vaginally or rectally infected women (FemCure)

Objectives: Spontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patien

SPAD array camera for localization based super resolution microscopy

Super resolution microscopy by localization is a stochastic based approach, where the resolution is determined by the localization accuracy [1] [2] [3]. The accuracy of localization heavily depends on the statistics of the data obtained with a camera during imaging. Current state of the art EMCCD (electron multiplying charge coupled device) cameras have frame rates up to 200 fps and hence a limited temporal resolution between frames. This can lead to ambiguities in localization. For example, a single fluorescent spot appearing at the same location in two successive frames is not considered for localization, because it is not clear, whether the spot arises from a single fluorophore in ON state for a long time or from two adjacent fluorophores, which switches ON and OFF. In this work, we explore for the first time the use of a single-photon counting SPAD (single photon avalanche diodes) array camera for super resolution microscopy. These cameras can provide high frame rates (up to 375000 fps), with improved temporal resolution between the frames, enabling a more accurate view of events that can be precisely tracked over time. The rich information obtained from such large number of frames leads to more accurate statistical estimations for overcoming the current ambiguities in localization. Also, SPAD array cameras are capable of reading frames having pixels depth of 1-bit. [4]. Such, a fine granularity enables the user to add any number of frames for identifying and localizing individual events with a very high accuracy. SPADs have been success fully used in performing time-resolved imaging measurements like FLIM (fluorescence life time imaging measurements). This allows us to extend the possibility of performing FLIM and super resolution imaging simultaneously. As a result, two different fluorophores can be separated based on their unique life times, enabling multi-channel operations using a single camera. An example of a preliminary image captured using a SPAD array camera is depicted in Figure

Social networks in relation to self-reported symptomatic infections in individuals aged 40-75 - the Maastricht study.

Most infections are spread through social networks (detrimental effect). However, social networks may also lower infection acquisition (beneficial effect). This study aimed to examine associations between social network parameters and prevalence of self-reported upper and lower respiratory, gastrointestinal and urinary tract infections in a population aged 40-75