Construction and evaluation of an automated flow injection-stopped flow analyser for multipoint reaction rate spectrophotometric methods. Determination of ammonia nitrogen, creatinine and phosphate

The construction and evaluation of a fully automated Flow Injection-Stopped Flow (FI-SF) spectrophotometric analyser is described. A microcomputer (Rockwell AIM 65) is used to control the analyser (sample injection, stop and start of the pump) through a suitable interface. Data acquisition is achieved using a 12 bit ADC card and a suitable subroutine in 6502 assembly language, allowing data sampling at a frequency of 7.5 kHz. The measurement interface and software were evaluated using a voltage ramp generator. A precision of 0.02-1.1% RSD (N =10) was obtained for voltage ramps in the range of 1-37 mVs-1. The FI-SF analyser was evaluated in routine analysis by developing FI-SF kinetic spectrophotometric methods for the determination of ammonia nitrogen (20-250 ppm, 0.4-2.5% RSD) based on the Berthelot reaction, creatinine (20-220 ppm, 0.9-3.6% RSD) based on the Jaffé reaction, and phosphate (5-30 ppm, 1.0-3.3% RSD) based on the phosphomolybdenum blue reaction. The reaction rate is measured by linear fitting of multiple absorbance readings vs time. Algorithms for automated estimation of the residence time, the linear range of the reaction curve, and data treatment are presented

Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes

Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death : Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials

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

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

A new multiresidue method for the determination of multiclass pesticides, degradation products and PCBs in water using LC–MS/MS and GC–MS^(<i>n</i>) systems

<div><p>A new multiresidue method for the determination of more than 200 pesticides and degradation products with distinct physicochemical properties and 13 polychlorinated biphenyls (PCBs) in water was developed and statistically validated. The method includes solid phase extraction using Oasis HLB cartridges and analysis using liquid chromatography tandem mass spectrometry (LC–MS/MS) and gas chromatography tandem mass spectrometry (GC–MS/MS) for pesticides and GC–MS for PCBs. The method was validated at different concentration levels for pesticides (1, 0.1 and 0.01 μg L⁻¹) and PCBs (0.1 μg L⁻¹) (five replicates) by assessing the following parameters: accuracy, precision, limit of quantification and linearity. Calibration curves were established for all analytes and regression analysis was performed at 95% confidence level. About 4.1% of the analytes had a recovery less than 60%, 5% from 60 to 70%, 84% from 70 to 120% and 6.8% from 120 to 140%. Acrinathrin had the lowest recoveries among all analytes studied both in LC and GC systems. In terms of pesticide class, lowest recoveries were for pyrethrins, aryloxyphenoxypropionic acids, cyclodienes and organochlorines. For PCBs, recovery ranged from 45.4% for deca-substituted PCB-209, to 105% for di-substituted PCB-11. The developed method was applied for the determination of pesticide residues in 73 samples of groundwater intended for irrigation purposes from three regions in Greece: (1) Prefecture of Messinia, Peloponesse; (2) Prefecture of Heraklion, Crete; and (3) Prefecture of Lasithi, Crete, during the period of November 2011 to November 2013. Eleven samples were found positive for pesticide residues, with ethalfluralin being the most frequently detected pesticide.</p></div

Validation and uncertainty estimation for conformity declaration of a method to assess the stability of nitrocellulose-based propellants

The scope of the present study was to develop and validate a rapid and precise method for the evaluation the stability and the chemical life of nitrocellulose-based propellants which contain as stabilizers diphenylamine, N-nitrosodiphenylamine, 2-nitrodiphenylamine, 4-nitrodiphenylamine and ethyl centralite. This was made by using the calculation of the weight percentage concentration (% w/w) of the initial effective stabilizer, the calculation of the weight percentage concentration (% w/w) of the effective stabilizer after artificial ageing, as well as the reduction of the concentration as a % percentage. All crucial parameters were investigated and optimized. The validation and the uncertainty estimation of the method was based on the Eurachem Guidelines. The recovery of the method was found higher than 95% and the RSD values were found less than 10%. The ageing procedure was found to be the most important factor influencing the uncertainty. The present study describes a very important procedure for ammunition management and the way to provide a declaration of conformity for safe use and storage