A clinical laboratory approach to severe sepsis : The changing role of laboratory medicine in clinical decision support during management of septicaemia.

epsis has a different meaning to the surgeon, physician and intensivist than the clinical microbiologist. Understanding the difference between a front line clinician’s diagnosis and determination of the microbial cause of severe sepsis is the key to unlocking the contribution of the clinical laboratory to critical decision support for septicaemic patients. Correct and effective use of blood culture, other culture and non-culture based methods of determining aetiology, followed by monitoring progress in severe sepsis are time-critical support measures for treatment decisions. Nucleic acid amplification techniques and MALDI-TOF mass spectrometer use have sped up the interval between blood culture inoculation and determination of a definitive aetiology. However, the aetiology can only rarely be determined soon enough to direct presumptive antibiotic choice in severe sepsis. More often, presumptive antibiotic and supportive care decisions have to be made with guidance from guidelines, clinical trial results and local laboratory-derived epidemiology. The contribution of the clinical microbiology laboratory is therefore more often in refinement of antibiotic treatment and the monitoring of progress. Until emerging laboratory technology has more to offer in the immediate assessment of severe sepsis, the clinical microbiologist will continue to play a mainly supportive role as a member of a multidisciplinary team. This is likely to change as a range of systems biology tools start to make an impact on the clinical laboratory.DOI: http://dx.doi.org/10.4038/sljid.v3i1.5150 </p

Deployable Laboratory Response to Influenza Pandemic; PCR Assay Field Trials and Comparison with Reference Methods

Background: The influenza A/H1N1/09 pandemic spread quickly during the Southern Hemisphere winter in 2009 and reached epidemic proportions within weeks of the official WHO alert. Vulnerable population groups included indigenous Australians and remote northern population centres visited by international travellers. At the height of the Australian epidemic a large number of troops converged on a training area in northern Australia for an international exercise, raising concerns about their potential exposure to the emerging influenza threat before, during and immediately after their arrival in the area. Influenza A/H1N1/09 became the dominant seasonal variant and returned to Australia during the Southern winter the following year. Methods: A duplex nucleic acid amplification assay was developed within weeks of the first WHO influenza pandemic alert, demonstrated in northwestern Australia shortly afterwards and deployed as part of the pathology support for a field hospital during a military exercise during the initial epidemic surge in June 2009. Results: The nucleic acid amplification assay was twice as sensitive as a point of care influenza immunoassay, as specific but a little less sensitive than the reference laboratory nucleic acid amplification assay. Repetition of the field assay with blinded clinical samples obtained during the 2010 winter influenza season demonstrated a 91.7% congruence with the reference laboratory method. Conclusions: Rapid in-house development of a deployable epidemic influenza assay allowed a flexible laboratory response, effective targeting of limited disease control resources in an austere military environment, and provided the public health laboratory service with a set of verification tools for resource-limited settings. The assay method was suitable for rapid deployment in time for the 2010 Northern winter

Preprints Perspectives: A Panel Discussion

Celebrate Open Access Week 2020 with the Thomas Jefferson University Libraries.Join our four experienced panelists to discuss issues such as: how publishing preprints can benefit authors, current best practices for preprint servers, ethical and legal considerations regarding the use of preprints, and the intersection of preprints and Covid-19 scholarship

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

Meat Intake and the Dose of Vitamin B3 - Nicotinamide:Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Meat and vitamin B 3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B 3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives) may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B 3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress