Forensic DNA databases in European countries: is size linked to performance?

The political and financial investments in the implementation of forensic DNA databases and the ethical issues related to their use and expansion justify inquiries into their performance and general utility. The main function of a forensic DNA database is to produce matches between individuals and crime scene stains, which requires a constant input of individual profiles and crime scene stains. This is conditioned, among other factors, by the legislation, namely the criteria for inclusion of profiles and the periods of time and conditions for their retention and/or deletion. This article aims to provide an overview of the different legislative models for DNA databasing in Europe and ponder if wider inclusion criteria – and, consequently, database size – translates into more matches between profiles of crime scene stains and included individuals (performance ratio). The legislation governing forensic DNA databases in 22 countries in the European Union was analysed in order to propose a typology of two major groups of legislative criteria for inclusion/retention of profiles that can be classified as having either expansive effects or restrictive effects. We argue that expansive criteria for inclusion and retention of profiles do not necessarily translate into significant gains in output performance.MES -Ministry of Education and Science(SFRH/BPD/34143/2006)info:eu-repo/semantics/publishedVersio

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Brief report: Group 3 innate lymphoid cells in human enthesis

Objective: Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthropathy (SpA). It was investigated whether normal and injured human enthesis, the key target tissue in early SpA, harboured ILC3s in entheseal soft tissue (EST) and adjacent peri-entheseal bone (PEB). Methods: Interspinous ligament and spinous process bone was collected from donors with no systemic inflammatory disease, enzymatically digested and immunophenotyped. The immunological profile of entheseal cells was examined and the transcriptional profile of sorted ILC3s was compared to those isolated from SpA synovial fluid. To assess the ability of entheseal tissue to produce IL-17 and IL-22 entheseal digests were stimulated with IL-23 and IL-1β. Osteoarthritic and ruptured Achilles tissue was examined histologically. Results: Compared to peripheral blood, human EST had a higher proportion of ILCs (p=0.008), EST and PEB both had a higher proportion of NKp44+ ILC3s (p=0.001 and p=0.043). RORγt, STAT3 and IL-23R transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and SpA synovial fluid. Normal entheseal digests stimulated with IL-23/IL-1β upregulated IL17A transcript and histological examination of injured/damaged entheses showed RORγt expressing cells. Conclusion: This work shows that human enthesis harbours a resident population of ILC3s, with the potential to participate in spondyloarthropathy pathogenesis

Syndromic Surveillance for Influenzalike Illness in Ambulatory Care Setting

Detection algorithm using proxy data for a bioterrorism agent release and historical data for influenza was effective

Nucleotide sequence and chromosomal location of Cab -7, the tomato gene encoding the type II chlorophyll a/b-binding polypeptide of photosystem I

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43420/1/11103_2004_Article_BF00016015.pd

Evidence that tissue resident human enthesis γδ T-cells can produce IL-17A independently of IL-23R transcript expression

Objectives: Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of Î 3Î T-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated Î 3Î T-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. Methods: Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal Î 3Î T-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from Î 3Î T-cell subsets and analysed by qPCR. Entheseal Î 3Î T-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. Results: Entheseal Î 3Î T-cells were confirmed immunohistochemically with VÎ 1 and VÎ 2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal VÎ 2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the VÎ 1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both VÎ 1 and VÎ 2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the VÎ 1 subset following IL-23 stimulation. Conclusion: Spinal entheseal VÎ 1 and VÎ 2 subsets are tissue resident cells with inducible IL-17A production with evidence that the VÎ 1 subset does so independently of IL-23R expression