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Current practice is to report and manage likely pathogenic/pathogenic variants in a given cancer susceptibility gene as though having equivalent penetrance, despite increasing evidence of intervariant variability in risk associations. Using existing variant interpretation approaches, largely based on full-penetrance models, variants in which reduced penetrance is suspected may be classified inconsistently and/or as variants of uncertain significance. We aimed to develop a national consensus approach for such variants within the Cancer Variant Interpretation Group UK (CanVIG-UK) multidisciplinary network.

Single-step trans-vertical moulds have been shown to increase the throughput of automated mineralogy systems. Owing to the small particle size of iron ore grains in the -200 mesh size fraction (<75 µm), not all of the surface area on a mould is needed for measurement in achieving good statistical representation. Trimming the excess area of a mould results in superfluous material being removed, leaving only the necessary analyte. This allows maximum packing in the sample chamber and promotes efficiency by increasing the quantity of samples that can fit in a newly designed trans-vertical adapter for an FEI MLA™ 650 field emission gun SEM. The analysis was completed using a newly designed sample block holder capable of holding 98 samples. This study represents the most expedient method yet reported to prepare well-polished samples and analyse them in a timely manner that can allow for quicker results in process mineralogy.

Scanning Electron Microscope–Mineral Liberation Analysis (SEM–MLA) can be used to discriminate between hematite and magnetite in iron ores. However, achieving backscattered electron (BSE) segmentation between the two minerals is difficult for particles =75 µm using typical preparation and analysis methods for the MLA method based on a tungsten filament SEM (Quanta 400) with 25 kV high voltage. Preparing iron ore sample mounts using a slow-speed polishing method, and conducting the experiment on a field emission gun SEM–MLA (Quanta 650) with the high voltage setting lowered to 15 kV reduces instrument noise and results in very clean BSE images and segmentation. This method requires new X-ray standards for each mineral at 15 kV because of major changes in the spectra at lower kV. However, once these X-ray spectra are added to the mineral reference list, effective segmentation can be achieved and an accurate analysis obtained.

ABSTRACTSingle-step trans-vertical moulds have been shown to increase the throughput of automated mineralogy systems. Owing to the small particle size of iron ore grains in the −200 mesh size fraction (<75 µm), not all of the surface area on a mould is needed for measurement in achieving good statistical representation. Trimming the excess area of a mould results in superfluous material being removed, leaving only the necessary analyte. This allows maximum packing in the sample chamber and promotes efficiency by increasing the quantity of samples that can fit in a newly designed trans-vertical adapter for an FEI MLA™ 650 field emission gun SEM. The analysis was completed using a newly designed sample block holder capable of holding 98 samples. This study represents the most expedient method yet reported to prepare well-polished samples and analyse them in a timely manner that can allow for quicker results in process mineralogy.

ABSTRACTScanning Electron Microscope–Mineral Liberation Analysis (SEM–MLA) can be used to discriminate between hematite and magnetite in iron ores. However, achieving backscattered electron (BSE) segmentation between the two minerals is difficult for particles ≤75 µm using typical preparation and analysis methods for the MLA method based on a tungsten filament SEM (Quanta 400) with 25 kV high voltage. Preparing iron ore sample mounts using a slow-speed polishing method, and conducting the experiment on a field emission gun SEM–MLA (Quanta 650) with the high voltage setting lowered to 15 kV reduces instrument noise and results in very clean BSE images and segmentation. This method requires new X-ray standards for each mineral at 15 kV because of major changes in the spectra at lower kV. However, once these X-ray spectra are added to the mineral reference list, effective segmentation can be achieved and an accurate analysis obtained.

A novel approach to creating a trans-vertical grain mount embedded in epoxy has been demonstrated through the creation of a new mounting mould, as well as a polisher adapter and sample holder for the Quanta 400 SEM. These rectangular moulds result in a sample that is 30 mm long × 10 mm high × 17 mm wide, thus leading to the ability to polish 10 samples at once. Up to 14 samples may fit in the SEM holder for analysis. This represents an increase in efficiency of over 50%, and with a slow-speed polishing method, the consumables used are reduced by at least a factor of 4. This has the potential to lead to significant financial savings. A comparison of mounting techniques using a −100+200 mesh size fraction of an iron-ore sample from Labrador demonstrates that this new mounting system removes any bias in analysis resulting from density stratification during the sample preparation. These moulds yield similar modal mineralogy abundances and standard deviation as the two-step trans-vertical method, but they are less labour-intensive to make and more efficient to analyse.

ObjectiveTo establish national clinical guidelines and integrated care pathways for five conditions (tuberous sclerosis (TS), Huntington's disease (HD), myotonic dystrophy (MD), neurofibromatosis type 1 (NF1), and Marfan syndrome (MS)) and audit their use in Scotland.DesignSystematic review of published reports followed by consensus conferences to prepare clinical guidelines and integrated care pathways. Structured review of medical records before and after introduction of integrated care pathways to document changes in practice. Survey of staff views on procedures adopted.SettingAll four clinical genetics centres in Scotland.ResultsProject resulted in reduced variation in practice across centres, improved data recording in medical records, and improved communication with other professional groups. A very poor evidence base for management of patients with the conditions studied was found.ConclusionsA collaborative structure for undertaking clinical research would improve the evidence base for current practice. National discussion of the boundaries of responsibility of care for the long term management of patients with these disorders is required. The integrated care pathway approach shows promise as a means of facilitating the development of audit within clinical genetics services.

Pulsed-field gel electrophoresis and flow dot-blot analysis have been used to construct a physical map of the q32-q34 region of chromosome 9, where one of the loci responsible for tuberous sclerosis (TSC1) has been mapped by genetic linkage. Five linked groups of markers have been defined by pulsed-field gel electrophoresis. The orientation of these groups and the order of markers within them were determined by hybridization to flow-sorted dot blots derived from a panel of cell lines of chromosome 9 translocations to place probes proximal or distal to each breakpoint. The local map order in 9q32-q34 derived by application of this combination of techniques is as follows: centromere-ALAD-1.3 Mb-ORM/20 kb/D9S16-GSN-250 kb-C5-HXB-1.9 Mb-D9S21-AK1-1.4 Mb-SPTAN1-ASS-800 kb-ABL-2 Mb-D9S10/350 Kb/DBH-telomere. Copyright 1993, 1999 Academic Press

This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of chromosome 9. A total of 124 markers were typed in the CEPH family DNAs by 14 contributing laboratories; of these, 42 loci are ordered on the map with likelihood support of at least 1000:1. The uniquely placed markers include 31 that can be typed by PCR. A further 28 markers that can be typed by PCR are approximately positioned on the map. Multilocus linkage analysis with CR1-MAP has produced male, female, and sex-averaged maps extending for 176, 237, and 209 cM, respectively, while sex-averaged maps produced with MAPMAKER and the multiple two-point program MAP extended for 170 and 129 cM, respectively. The male map contains only two intervals greater than 10 cM, and the mean genetic distance between the 42 uniquely placed loci is 4.3 cM. However, no markers were available to anchor the map at either telomere or the centromere. The results confirm the high level of interference suggested by chiasma maps of chromosome 9. Detailed meiotic breakpoints for three of the families are shown. These can be used to provide rapid placement of any new marker without the need for statistical analysis.

IntroductionFaecal Immunochemical Tests for haemoglobin (FIT) detect haemoglobin in stool (FHb). FIT has been advocated as a good ‘rule-out’ test for significant bowel disease in the symptomatic population (1). In this pilot study, we examined whether FIT may have a similar role in subjects enrolled in surveillance colonoscopy.MethodBetween 1stJune 2014 and Sept 30th2016, 15 consecutive months of surveillance patients were approached at Ninewells Hospital, and 3 consecutive months were approached at St Marks Hospital. Subjects were invited to complete a FIT test prior to their colonoscopy. FHb was measured by Blood Sciences, Ninewells Hospital using an OC-Sensor iO analyser (Eiken Chemical Co., Tokyo, Japan) with an analytic range of <10 to>200 µg Hb/g of faeces. Colonoscopy results were recorded and the diagnostic accuracy of the FIT test was examined.ResultsOf the 1103 patients approached, 643 returned a FIT kit. Four patients had known IBD and were excluded, leaving 639 (58%) in the study; age range 25–90 years (median 64 years, IQR 55–71) 54% were male. Indications for colonoscopy were: adenoma surveillance 312 (48.8%), genetic surveillance 152 (23.8%), other family history 84 (13.1%), cancer follow-up 72 (11.3%), other 19 (3.0%). Of the 639 patients, 46 were excluded from analysis of FIT test performance; 19 patients did not respond to or cancelled colonoscopy appointment, 8 did not attend colonoscopy, 3 patients were not fit to attend, 3 no valid FIT result, 1 cancelled by nurse, 1 had CT colonoscopy, 2 colonoscopy incomplete, 9 colonoscopies not complete by end of study. Of 593 patients who returned a FIT and completed colonoscopy only 7% had significant neoplasia (4 cancers (0.7%), 37 HRA (6.3%)) and 0.8% had IBD. 227/593 patients (38%) had undetectable FIT of whom 2.2% had significant neoplasia (one cancer (0.4%), 4 HRA (1.8%)) and 0.4% had IBD. 366/593 patients (62%) had detectable FIT of whom 9.9% had significant neoplasia (3 cancers (0.8%), 33 HRA (9.0%)) and 1.1% had IBD. Using a FIT cut off level of ‘not detectable’, gave a NPV of 99.6% for CRC and 97.8% for CRC+HRA. 36/41 cases of advanced neoplasia would have been detected. One CRC and 4 HRA would have been missed.ConclusionThe yield of significant neoplasia at surveillance colonoscopy was low. A negative FIT was recorded in over one third of subjects and could be used as a ‘rule-out’ test to avoid unnecessary surveillance colonoscopy, at the expense of missing a very small proportion of significant neoplasia.Reference. Mowat C, J Digby, Strachan JA, et al. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut2016 Sept;65(9):1463–9.Disclosure of InterestNone Declared

Genetic testing for hereditary haemochromatosis is likely to be a significant workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE gene associated with hereditary haemochromatosis have previously been detected using a number of methods including alterations in the restriction digest pattern of polymerase chain reaction (PCR) amplified products. An amplification refractory mutation system (ARMS) has been developed that will simultaneously detect both hereditary haemochromatosis mutations. Comparison of the results obtained from the analysis of 46 samples referred for hereditary haemochromatosis testing showed no discrepancies between ARMS and restriction enzyme digestion. Furthermore, consistent results were obtained by ARMS from both blood and buccal mouthwash samples. The ARMS test is quicker and less expensive in terms of consumables and scientist time than restriction enzyme analysis, and is therefore suited to the routine diagnostic analysis of hereditary haemochromatosis.