High-throughput analysis of tissue microarrays using automated desorption electrospray ionization mass spectrometry

Tissue microarrays (TMAs) are commonly used for the rapid analysis of large numbers of tissue samples, often in morphological assessments but increasingly in spectroscopic analysis, where specific molecular markers are targeted via immunostaining. Here we report the use of an automated high-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS) for the rapid generation and online analysis of high-density (6144 samples/array) TMAs, at rates better than 1 sample/second. Direct open-air analysis of tissue samples (hundreds of nanograms) not subjected to prior preparation, plus the ability to provide molecular characterization by tandem mass spectrometry (MS/MS), make this experiment versatile and applicable to both targeted and untargeted analysis in a label-free manner. These capabilities are demonstrated in a proof-of-concept study of frozen brain tissue biopsies where we showcase (i) a targeted MS/MS application aimed at identification of isocitrate dehydrogenase mutation in glioma samples and (ii) an untargeted MS tissue type classification using lipid profiles and correlation with tumor cell percentage estimates from histopathology. The small sample sizes and large sample numbers accessible with this methodology make for a powerful analytical system that facilitates the identification of molecular markers for later use in intraoperative applications to guide precision surgeries and ultimately improve patient outcomes

Clinical, Pathological, and Surgical Outcomes for Adult Pineoblastomas

Introduction Pineoblastomas are uncommon primitive neuroectodermal tumors that occur mostly in children; they are exceedingly rare in adults. Few published reports have compared the various aspects of these tumors between adults and children. Methods The authors report a series of 12 pineoblastomas in adults from 2 institutions over 24 years. The clinical, radiologic, and pathologic features and clinical outcomes were compared with previously reported cases in children and adults. Results Patient age ranged from 24 to 81 years, and all but 1 patient exhibited symptoms of obstructive hydrocephalus. Three patients underwent gross total resection, and subtotal resection was performed in 3 patients. Diagnostic biopsy specimens were obtained in an additional 6 patients. Pathologically, the tumors had the classical morphologic and immunohistochemical features of pineoblastomas. Postoperatively, 10 patients received radiotherapy, and 5 patients received chemotherapy. Compared with previously reported cases, several differences were noted in clinical outcomes. Of the 12 patients, only 5 (42%) died of their disease (average length of survival, 118 months); 5 patients (42%) are alive with no evidence of disease (average length of follow-up, 92 months). One patient died of unrelated causes, and one was lost to follow-up. Patients with subtotal resections or diagnostic biopsies did not suffer a worse prognosis. Of the 9 patients with biopsy or subtotal resection, 4 are alive, 4 died of their disease, and 1 died of an unrelated hemorrhagic cerebral infarction. Conclusions Although this series is small, the data suggest that pineoblastomas in adults have a less aggressive clinical course than in children

Designing assisted living technologies 'in the wild' : preliminary experiences with cultural probe methodology

Background There is growing interest in assisted living technologies to support independence at home. Such technologies should ideally be designed ‘in the wild’ i.e. taking account of how real people live in real homes and communities. The ATHENE (Assistive Technologies for Healthy Living in Elders: Needs Assessment by Ethnography) project seeks to illuminate the living needs of older people and facilitate the co-production with older people of technologies and services. This paper describes the development of a cultural probe tool produced as part of the ATHENE project and how it was used to support home visit interviews with elders with a range of ethnic and social backgrounds, family circumstances, health conditions and assisted living needs. Method Thirty one people aged 60 to 98 were visited in their homes on three occasions. Following an initial interview, participants were given a set of cultural probe materials, including a digital camera and the ‘Home and Life Scrapbook’ to complete in their own time for one week. Activities within the Home and Life Scrapbook included maps (indicating their relationships to people, places and objects), lists (e.g. likes, dislikes, things they were concerned about, things they were comfortable with), wishes (things they wanted to change or improve), body outline (indicating symptoms or impairments), home plan (room layouts of their homes to indicate spaces and objects used) and a diary. After one week, the researcher and participant reviewed any digital photos taken and the content of the Home and Life Scrapbook as part of the home visit interview. Findings The cultural probe facilitated collection of visual, narrative and material data by older people, and appeared to generate high levels of engagement from some participants. However, others used the probe minimally or not at all for various reasons including limited literacy, physical problems (e.g. holding a pen), lack of time or energy, limited emotional or psychological resources, life events, and acute illness. Discussions between researchers and participants about the materials collected (and sometimes about what had prevented them completing the tasks) helped elicit further information relevant to assisted living technology design. The probe materials were particularly helpful when having conversations with non-English speaking participants through an interpreter. Conclusions Cultural probe methods can help build a rich picture of the lives and experiences of older people to facilitate the co-production of assisted living technologies. But their application may be constrained by the participant’s physical, mental and emotional capacity. They are most effective when used as a tool to facilitate communication and development of a deeper understanding of older people’s needs

DNA damage and health effects in juvenile haddock exposed to sediment or produced water associated PAHs

Tilstandsundersøkelsene i Nordsjøen har det siste tiår vist gentoksiske effekter (DNA-addukter) i fisk samlet inn i områder med offshore olje- og gassvirksomhet. Kilden og identiteten til de gentoksiske forbindelsene har til nå ikke blitt identifisert. Målsetningen for prosjektet har vært å studere dannelsen av DNA-skade i hyse som utsettes for ulike petrogene eller pyrogene polyaromatiske hydrokarboner (PAH). Målet har vært å identifisere kildene til forurensningen som medfører DNA-addukter observert i hyse fanget rundt oljefeltene i Nordsjøen. Dannelsen av DNA-skade over tid i hyse under kronisk eksponering for PAH og andre oljehydrokarboner fra følgende kilder er blitt studert: Ekstrakter av produsert vann (Statfjord A); destillasjonsfraksjoner av råolje fra Gullfaks (representere oljebasert borevæske); pyrogene PAH. Denne rapporten presenterer resultatene av studiene på DNA addukter i hyse og et utvalg av andre biologiske effektparametre.The Condition Monitoring in the North Sea the last ten years have documented genotoxic effects (DNA adduct) in fish collected in areas with extensive offshore oil and gas activity. However, the source and identity of genotoxic compound has not been identified. The objective of this project has been to study the formation of DNA damage in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: Extracts of produced water (Statfjord A); distillation fractions of crude oil from Gullfaks (representing oil based drilling mud); pyrogenic PAH This report presents all the results from the study on DNA adducts and a selection of other biological effect parameters

Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas

Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion. Codeletion of 1p/19q traditionally evaluated by fluorescence in situ hybridization (FISH) cannot distinguish partial from whole-arm 1p/19q codeletion. Partial 1p/19q codeletion called positive by FISH is diagnostically a "false-positive" result. Chromosomal microarray (CMA) discriminates partial from whole-arm 1p/19q codeletion. Herein, we aimed to estimate the frequency of partial 1p/19q codeletion that would lead to a false-positive FISH result

Ancient DNA evidence for the ecological globalization of cod fishing in medieval and post-medieval Europe

Understanding the historical emergence and growth of long-range fisheries can provide fundamental insights into the timing of ecological impacts and the development of coastal communities during the last millennium. Whole-genome sequencing approaches can improve such understanding by determining the origin of archaeological fish specimens that may have been obtained from historic trade or distant water. Here, we used genome-wide data to individually infer the biological source of 37 ancient Atlantic cod specimens (ca 1050-1950 CE) from England and Spain. Our findings provide novel genetic evidence that eleventh- to twelfth-century specimens from London were predominantly obtained from nearby populations, while thirteenth- to fourteenth-century specimens were derived from distant sources. Our results further suggest that Icelandic cod was indeed exported to London earlier than previously reported. Our observations confirm the chronology and geography of the trans-Atlantic cod trade from Newfoundland to Spain starting by the early sixteenth century. Our findings demonstrate the utility of whole-genome sequencing and ancient DNA approaches to describe the globalization of marine fisheries and increase our understanding regarding the extent of the North Atlantic fish trade and long-range fisheries in medieval and early modern time

Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly

BACKGROUND: Sarcopenia is an important cause of morbidity and mortality in older adults, with immunosenescence and inflammation being possible underlying mechanisms. We investigated the relationship between latent cytomegalovirus (CMV) infection, Interleukin 6 (IL-6) levels, muscle size and strength in a group of healthy older community-dwelling people. METHODS: Participants were healthy volunteers from the Lothian Birth Cohort 1936 study. Participants had IL-6 level and CMV antibody titre measured at age 70 years and grip strength and a volumetric T1-weighted MRI brain scan (allowing measurement of neck muscle cross-sectional area (CSA)) at age 73. Markers of childhood deprivation were adjusted for in the analysis due to correlations between childhood deprivation and latent CMV infection. RESULTS: 866 participants were studied; 448 men (mean age 72.48 years, sd 0.70) and 418 women (mean age 72.51 years, sd 0.72). In men, CMV seropositivity was associated with smaller neck muscle CSA (p = 0.03, partial eta squared = 0.01), even after adjustment for IL-6 levels. Neck muscle CSA was not associated with CMV seropositivity in women, or CMV antibody titre or IL-6 level in either sex. Grip strength associated negatively with IL-6 level (right grip strength p<0.00001, partial eta squared 0.032 and left grip strength p<0.00001, partial eta squared 0.027) with or without adjustment for CMV serostatus or antibody titre. CMV status and antibody titre were not significantly associated with grip strength in either hand. CONCLUSION: These findings support the hypothesis that there is a relationship between markers of immunosenescence (i.e. CMV serostatus and IL6 level) and low muscle mass and strength and longitudinal studies in older cohorts are now required to investigate these relationships further

Ancient DNA evidence for the ecological globalization of cod fishing in medieval and post-medieval Europe

Understanding the historical emergence and growth of long-range fisheries can provide fundamental insights into the timing of ecological impacts and the development of coastal communities during the last millennium. Whole-genome sequencing approaches can improve such understanding by determining the origin of archaeological fish specimens that may have been obtained from historic trade or distant water. Here, we used genome-wide data to individually infer the biological source of 37 ancient Atlantic cod specimens (ca 1050-1950 CE) from England and Spain. Our findings provide novel genetic evidence that eleventh- to twelfth-century specimens from London were predominantly obtained from nearby populations, while thirteenth- to fourteenth-century specimens were derived from distant sources. Our results further suggest that Icelandic cod was indeed exported to London earlier than previously reported. Our observations confirm the chronology and geography of the trans-Atlantic cod trade from Newfoundland to Spain starting by the early sixteenth century. Our findings demonstrate the utility of whole-genome sequencing and ancient DNA approaches to describe the globalization of marine fisheries and increase our understanding regarding the extent of the North Atlantic fish trade and long-range fisheries in medieval and early modern times