RAS screening in colorectal cancer: a comprehensive analysis of the results from the UK NEQAS colorectal cancer external quality assurance schemes (2009–2016)

Abstract

Evidence strongly indicates that extended RAS testing should be undertaken in mCRC patients, prior to prescribing anti-EGFR therapies. With more laboratories implementing testing, the requirement for External Quality Assurance schemes increases, thus ensuring high standards of molecular analysis. Data was analysed from 15 United Kingdom National External Quality Assessment Service (UK NEQAS) for Molecular Genetics Colorectal cancer external quality assurance (EQA) schemes, delivered between 2009 and 2016. Laboratories were provided annually with nine colorectal tumour samples for genotyping. Information on methodology and extent of testing coverage was requested, and scores given for genotyping, interpretation and clerical accuracy. There has been a sixfold increase in laboratory participation (18 in 2009 to 108 in 2016). For RAS genotyping, fewer laboratories now use Roche cobas®, pyrosequencing and Sanger sequencing, with more moving to next generation sequencing (NGS). NGS is the most commonly employed technology for BRAF and PIK3CA mutation screening. KRAS genotyping errors were seen in ≤10% laboratories, until the 2014–2015 scheme, when there was an increase to 16.7%, corresponding to a large increase in scheme participants. NRAS genotyping errors peaked at 25.6% in the first 2015–2016 scheme but subsequently dropped to below 5%. Interpretation and clerical accuracy scores have been consistently good throughout. Within this EQA scheme, we have observed that the quality of molecular analysis for colorectal cancer has continued to improve, despite changes in the required targets, the volume of testing and the technologies employed. It is reassuring to know that laboratories clearly recognise the importance of participating in EQA schemes.

http://ift.tt/2sS1YXf

Giardia duodenalis and Cryptosporidium spp. as contaminant protozoa of the main rivers of western Romania: genetic characterization and public health potential of the isolates

Abstract

The objective of this study was to establish the prevalence, contamination level, and public health significance of Giardia duodenalis and Cryptosporidium spp. in the primary rivers of western Romania. A total of 53 sampling points in the 24 most important western Romanian rivers in four counties (Arad, Bihor, Caraș-Severin, and Timiș) were investigated from March to September 2016. Surface water samples were collected by microfiber filtration. Cryptosporidium and Giardia (oo)cysts were isolated using immunomagnetic separation (IMS) according to the USEPA 1623 method and, after staining with fluorescently labeled (FITC) monoclonal antibodies, were identified and counted under a microscope. The Cryptosporidium and Giardia (oo)cysts were identified to species and assemblage/sub-assemblage level through the nested PCR–RFLP procedure targeting the 18S ribosomal RNA and gdh genes, respectively. PCR-based techniques were utilized for all water samples. Overall, 22 samples (41.5%) were determined to be positive for Giardia cysts (ranging from 0.05 to 300 cysts per liter), and four samples (7.5%) tested positive for Cryptosporidium oocysts (0.17–48 oocysts/l). G. duodenalis was molecularly identified in 13 water samples (24.5%), indicating the presence of the sub-assemblage A-II (n = 12) and assemblage E (n = 1). PCR–RFLP showed that two samples (3.8%) contained Cryptosporidium DNA, and the identified species were Cryptosporidium parvum and Cryptosporidium canis. All positive results were successfully confirmed by DNA sequencing. Subtyping of the zoonotic C. parvum isolate based on sequence analysis of the GP60 gene revealed the occurrence of the IIaA16G1R1 subtype. The results of this study highlight considerable contamination of river waters with pathogenic Giardia spp. and Cryptosporidium spp., suggesting a potential risk for the public and animal health. This report presents the first extended published description of the presence of Giardia spp. and Cryptosporidium spp. in the aquatic environment in Romania.

http://ift.tt/2tc43Am

Effects of residue incorporation and plant growth on soil labile organic carbon and microbial function and community composition under two soil moisture levels

Abstract

This study investigates the effects of residue incorporation coupled with plant growth and soil moisture level on wheat biomasses, soil nutrients, labile organic carbon (LOC), microbial metabolic profiles, and community composition. Four management practices were used in a 180-day pot experiment: (1) control (CON), (2) maize (Zea mays L.) residue incorporation without plants (MR), (3) wheat (Triticum aestivum L.) plants without maize residue (WP), and (4) maize residue incorporation with wheat plants (MRWPs). Each management practice included soil moisture at both 40 and 80% of field capacity. At wheat harvest, soil nutrient contents in the WP and MRWP treatments were significantly lower than in the CON and MR treatments. In comparison with the CON treatment, MR, WP, and MRWP treatments resulted in 35, 23, and 67% increases in dissolved organic carbon content; 17, 12, and 34% increases in hot-water extractable organic carbon content; and 78, 50, and 150% increases in microbial biomass carbon content. Furthermore, microbial utilizations of carboxylic acids and polymer carbon sources in the MR, WP, and MRWP treatments were 261 and 88%, 239 and 105%, and 300 and 126% higher than in the CON treatment. The MR and CON treatments had similar phospholipid fatty acid (PLFA) content but the WP and MRWP treatments had significantly increased gram-negative content and changes to community composition compared with the CON and MR treatments. The wheat biomass, LOC, and PLFA contents significantly increased with greater soil moisture. Overall, these results suggest an additive effect of residue incorporation and plant growth on LOC contents, primarily due to the changes in microbial utilization of carbon sources and community composition.

http://ift.tt/2tLD6An

Air pollution and hospital visits for acute upper and lower respiratory infections among children in Ningbo, China: A time-series analysis

Abstract

Acute upper and lower respiratory infections are main causes of mortality and morbidity in children. Air pollution has been recognized as an important contributor to development and exacerbation of respiratory infections. However, few studies are available in China. In this study, we investigated the short-term effect of air pollution on hospital visits for acute upper and lower respiratory infections among children under 15 years in Ningbo, China. Poisson generalized models were used to estimate the associations between air pollution and hospital visits for acute upper and lower respiratory infections adjusted for temporal, seasonal, and meteorological effects. We found that four pollutants (PM_2.5, PM₁₀, NO₂, and SO₂) were significantly associated with hospital visits for acute upper and lower respiratory infections. The effect estimates for acute upper respiratory infections tended to be higher (PM_2.5 ER = 3.46, 95% CI 2.18, 4.76; PM₁₀ ER = 2.81, 95% CI 1.93, 3.69; NO₂ ER = 11.27, 95% CI 8.70, 13.89; SO₂ ER = 15.17, 95% CI 11.29, 19.19). Significant associations for gaseous pollutants (NO₂ and SO₂) were observed after adjustment for particular matter. Stronger associations were observed among older children and in the cold period. Our study suggested that short-term exposure to outdoor air pollution was associated with hospital visits for acute upper and lower respiratory infections in Ningbo.

http://ift.tt/2tcdXlA

Disease genetics: Repeat expansion disorders — going through a phase

Nature Reviews Genetics. doi:10.1038/nrg.2017.54

Author: Dorothy Clyde

http://ift.tt/2tLrPjU

Synthetic lethality and cancer

Nature Reviews Genetics. doi:10.1038/nrg.2017.47

Authors: Nigel J. O'Neil, Melanie L. Bailey & Philip Hieter

http://ift.tt/2tL1sKA

Cancer epigenetics: Therapy-induced transcription is cryptically widespread

Nature Reviews Genetics. doi:10.1038/nrg.2017.53

Author: Darren J. Burgess

http://ift.tt/2tKZJVN