An optimised small-scale sample preparation workflow for historical dye analysis using UHPLC-PDA applied to Scottish and English Renaissance embroidery

A sample preparation workflow for historical dye analysis based on 96 well plates and filtration by centrifugation was developed. It requires less sample and the introduced error is decreased, making it useful for culturally important objects. A sample preparation workflow for historical dye analysis requiring less sample has been developed. Samples as small as 0.01 ± 0.005 mg have been successfully analysed and high percentage recoveries (>85%), more automation and shorter preparation time have been achieved using filtration by centrifugation and only one manual transfer. The optimised workflow based on 96 well plates together with the shorter UHPLC method developed makes dye analysis data collection faster from unprocessed sample to result, facilitating the creation of larger datasets and application of chemometric approaches. The method was evaluated on 85 samples from 12 dye sources (RSD < 5.1%, = 5) as well as 22 samples from a 17 century embroidered stomacher from the National Museums Scotland (NMS) collection

Gene expression profiling and expanded immunohistochemistry tests to guide selection of chemotherapy regimens in breast cancer management: a systematic review

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7064 citations, of which 41 citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision-making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomised controlled trial data

Levels of DNA methylation vary at CpG sites across the BRCA1 promoter, and differ according to triple negative and "BRCA-like" status, in both blood and tumour DNA

Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies

Using a Delphi process to determine optimal care for patients with pancreatic cancer

Aim Overall 5-year survival for pancreatic cancer is ~5%. Optimising the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. Methods Using a Delphi process, a multi-disciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one (no importance/disagree) to 10 (very important/agree) the factors. The mean and coefficient of variation scores were calculated and categorised into three levels of importance. Results Overall 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from 9 disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multi-disciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and inter- disciplinary variation in views about MDT membership and roles. Conclusion Overall the opinions of Australian health professionals reflect international guideline recommended care; however they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multi-disciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

A stitch in time: 300 years of visible mending

Does your favourite jumper have a hole in it? Seems a shame to get rid of a lovely piece of clothing because of a little tear, right? How about mending it! Senior Curator of Historic Textiles Helen Wyld talks us through some of the historic repairs in our textiles collection. You never know, it might inspire you to pick up a needle and thread

Catalogue entry: Mortlake Workshop, after Francis Cleyn (born in Rostock, 1582; died in London, 1658), designer, after Pieter Coecke van Aelst (1502-1550) and Bernard van Orley (c.1492-c.1541) The Return of Sarah by the Egyptians, c.1658-60

The Paston Treasure, a spectacular painting now held at Norwich Castle Museum, depicts objects from the collections of a local landed family. The Pastons established one of the most extensive cabinets of rarities and curiosities in seventeenth-century England—it boasted no fewer than six hundred decorative art objects, including shell cups, crystal vessels, a pair of crocodiles, gemstones, musical instruments, and paintings. During the 1660s, either Sir William Paston or his son Robert Paston, first Earl of Yarmouth, and his wife, Rebecca (née Clayton), commissioned a picture that functions as a kind of heirloom portrait, celebrating the family’s legacy of collecting, while providing a tantalizing glimpse of the riches they accumulated over the generations. This volume accompanies an exhibition that unites objects depicted in the painting for the first time in nearly three hundred years. This multidisciplinary exposition of the painting, the Paston family, and their world draws on a wide range of fields, including history of art and of collections, technical art history, musicology, and history of science, as well as the broader social and cultural history of the seventeenth century. Technical analysis has made it possible to delve beneath the surface of the painting itself, revealing unexpected changes during its production and illuminating the material history of a masterwork that has in the past defied firm attribution, dating, and interpretation. Using the painting as a portal to the history of the collection and its owners, The Paston Treasure: Microcosm of the Known World weaves together narratives of the family and their possessions, the objects, and the institutions that eventually acquired them

The Storrar Coverlet: uncovering a story of Baltic trade

This beautiful double-weave coverlet, dated 1729, was recently acquired by National Museums Scotland from the collection of a family from Fife in the east of Scotland. In the family’s possession for generations, the coverlet has been passed down, tradition has it, from mother to daughter. The double-weave technique was used in the eighteenth century for so-called Scotch carpets and other locally produced domestic textiles, and historically the coverlet has been described as of Scottish manufacture. Visually, however, the design, with its repeating motif of geometric forms and birds, is far closer to traditional Swedish double weave textiles known as finnvaev. Such textiles survive from as early as the Viking era, and their distinctive design characteristics were established in the Renaissance, partly through influence from southern Europe. In Sweden, such coverlets were often made to mark a wedding or family event and, so, incorporated dates; they were often handed down through the female line. Research is currently underway on the history of the Storrar family, the early provenance of the coverlet, and its physical characteristics to establish its relationship to traditional Swedish production and to the Scottish textile industry. The east coast of Fife where the coverlet comes from has historic trading links with the Baltic, and we are excited about what the coverlet will reveal about the rich history of trade, cultural exchange, and the transfer of skills between Scotland and Scandinavia.The double-weave technique has been used for woolen coverlets and similar textiles in a range of other contexts, including the North American coverlet tradition—almost certainly arriving via immigration from Scandinavia. An examination of this transfer of a traditional skill to a new continent could potentially help establish the status of the Storrar coverlet, between Scotland and Sweden