Performance assessment of a 125 human plasma peptide mixture stored at room temperature for multiple reaction monitoring-mass spectrometry

Synthetic peptides are a critical requirement for the development and application of targeted mass spectrometry (MS)-based assays for the quantitation of proteins from biological matrices. Transporting synthetic peptides on dry ice from one laboratory to another is costly and often difficult because of country-specific import and export regulations. Therefore, in this study, we assessed the impact of leaving a lyophilized mixture consisting of 125 peptides at room temperature for up to 20 days, and we assessed the effect on the quantitative performance of multiple reaction monitoring-MS (MRM-MS) assays. The findings suggest that there are no significant differences in the MRM-MS results for the time points assessed in this study (up to 20 days). All the calibration curves and quality control (QC) samples met the acceptance criteria for precision and accuracy (raw data are available via the public MS data repository PanoramaWeb, identifier: /MRM Proteomics/2020_BAK125_RT). The number of endogenous proteins quantifiable across five plasma samples was consistently between 87 and 99 out of 125 for all time points. Moreover, the coefficients of variation (CVs) calculated for the majority of peptide concentrations across all samples and time points were <5%. In addition, a lyophilized peptide mixture was transported from Canada to Iceland without dry ice. The results showed that there was no significant difference in the quantitative performance, with the determined concentrations of most proteins in the samples falling within 30% between the analyses performed on the same three plasma samples in Iceland and those in Canada. Overall, a comparison of the results obtained in Canada and in Iceland indicated that the peptides were stable under the conditions tested and also indicated that shipping lyophilized peptide mixtures without dry ice, but in the presence of sufficient desiccant material, could be a feasible option in cases where transport difficulties may arise or dry-ice sublimation may occur.Proteomic

Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease

AIMS: To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols. METHODS AND RESULTS: We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75-2.31, P = 9.8 × 10-23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49-1.59, P = 1.1 × 10-154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10-4). CONCLUSIONS: Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis

Laparoscopic versus open left lateral segmentectomy

<p>Abstract</p> <p>Background</p> <p>Laparoscopic liver surgery is becoming increasingly common. This cohort study was designed to directly compare perioperative outcomes of the left lateral segmentectomy via laparoscopic and open approach.</p> <p>Methods</p> <p>Between 2002 and 2006 43 left lateral segmentectomies were performed at King's College Hospital. Those excluded from analysis included previous liver resections, polycystic liver disease, liver cirrhosis and synchronous operations. Of 20 patients analysed, laparoscopic (n = 10) were compared with open left lateral segmentectomy (n = 10). Both groups had similar patient characteristics.</p> <p>Results</p> <p>Morbidity rates were similar with no wound or chest infection in either group. The conversion rate was 10% (1/10). There was no difference in operating time between the groups (median time 220 minutes versus 179 minutes, p = 0.315). Surgical margins for all lesions were clear. Less postoperative opiate analgesics were required in the laparoscopic group (median 2 days versus 5 days, p = 0.005). The median postoperative in-hospital stay was less in the laparoscopic group (6 days vs 9 days, p = 0.005). There was no mortality.</p> <p>Conclusion</p> <p>Laparoscopic left lateral segmentectomy is safe and feasible. Laparoscopic patients may benefit from requiring less postoperative opiate analgesia and a shorter post-operative in-hospital stay.</p

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Holocene Cyclic Records of Ice-Rafted Debris and Sea Ice Variations on the East Greenland and Northwest Iceland Margins

The dynamics of the Greenland Ice Sheet and drift of sea ice from the Arctic Ocean reaching Denmark Strait are poorly constrained. We present data on the provenance of Fe oxide detrital grains from two cores in the Denmark Strait area and compare the Fe grain source data with other environmental proxies in order to document the variations and potential periodicities in ice-rafted debris delivery during the Holocene. Based on their Fe grain geochemistry, the sediments can be traced to East Greenland sources and to more distal sites around the Arctic Basin. On the Holocene time scales of the two cores, sea ice biomarker (IP25) data, and quartz weight percent reveal positive associations with T°C and inverse associations with biogenic carbonate wt%. Trends in the data were obtained from Singular Spectrum Analysis (SSA), and residuals were tested for cyclicity. Trends on the environmental proxies explained between 15 and 90% of the variance. At both sites the primary Fe grain sources were from Greenland, but significant contributions were also noted from Banks Island and Svalbard. There is a prominent cyclicity of 800 yrs as well as other less prominent cycles for both Greenland and arctic sources. The Fe grain sources from Greenland and the circum-Arctic Ocean are in synchronization, suggesting that the forcings for these cycles are regional and not local ice sheet instabilities

Accounting: A General Commentary on an Empirical Science

Many researchers have questioned the view of accounting as a science. Some maintain that it is a service activity rather than a science, yet others entertain the view that it is an art or merely a technology. While it is true that accounting provides a service and is a technology (a methodology for recording and reporting), that fact does not prevent accounting from being a science. Based upon the structure and knowledge base of the discipline, this paper presents the case for accounting as an empirical science

Parameterized verification of the FLASH cache coherence protocol by compositional model checking

Abstract. We consider the formal verification of the cache coherence protocol of the Stanford FLASH multiprocessor for N processors. The proof uses the SMV proof assistant, a proof system based on symbolic model checking. The proof process is described step by step. The protocol model is derived from an earlier proof of the FLASH protocol, using the PVS system, allowing a direct comparison between the two methods.

Holocene centennial to millennial-scale climatic variability: Evidence from high-resolution magnetic analyses of the last 10 cal kyr off North Iceland (core MD99-2275)

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