National Library of Scotland

Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.

Background: complex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: A candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 MTBC isolates with paired whole-genome sequencing and phenotypic drug susceptibility testing data were amassed from 45 countries. For each mutation, a contingency table of binary phenotypes and presence or absence of the mutation computed positive predictive value, and Fisher's exact tests generated odds ratios and Benjamini-Hochberg corrected p-values. Mutations were graded as Associated with Resistance if present in at least 5 isolates, if the odds ratio was >1 with a statistically significant corrected p-value, and if the lower bound of the 95% confidence interval on the positive predictive value for phenotypic resistance was >25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: 15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: This first WHO endorsed catalogue of molecular targets for MTBC drug susceptibility testing provides a global standard for resistance interpretation. Its existence should encourage the implementation of molecular diagnostics by National Tuberculosis Programmes. Funding: UNITAID, Wellcome, MRC, BMGF.

Summary Upland biotopes have conservation importance for their typical plant and animal species. Recently, the condition of upland habitats has deteriorated with associated declines in many upland birds. Grazing by increased densities of sheep has been implicated in these changes. Studies in lowland agricultural land have shown a link between declines in bird populations and the availability of arthropod prey. We studied the effect of three grazing regimes and an ungrazed control, each replicated six times in a total of 24 3·3‐ha plots, on the numbers and overall biomass of foliar arthropods in upland grassland in the Southern Highlands. The three grazed treatments of the experiment were stocked with the commercial stocking density of sheep, one‐third of the commercial stocking density by sheep only and one‐third of the commercial stocking density by sheep and cattle. Arthropod groups recognized as components of the diet of moorland birds were sampled by motorized suction sampler and sweep net. Arthropod numbers were unaffected by grazing treatments 6 months after grazing commenced. Significant grazing treatment effects on spiders, bugs and beetles were observed in years 2 and 3, with higher numbers in the less‐grazed treatments, but no such effect on brachyceran flies, caterpillars and craneflies. A residual maximum likelihood (REML) analysis related the numbers of spiders, bugs, beetles, craneflies and caterpillars to either the stocking density of sheep or an interaction of sheep with year. The analysis related bugs and brachyceran flies to an interaction between cattle stocking density and year. Estimated total biomass of foliar arthropods increased significantly with decreasing grazing intensity in years 2 and 3 and biomass in the ungrazed treatment was approximately twice that in the commercially grazed treatment. The REML analysis related biomass to the stocking density of sheep and both the stocking density of sheep and of cattle in an interaction with year. Synthesis and applications . We demonstrated that the stocking density and inclusion of cattle grazing affects the numbers and biomass of particular foliar arthropods in the uplands of Scotland. Grazing management is important not only for the conservation of arthropods per se but also as food for insectivorous birds of conservation concern.

Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics.

OBJECTIVES: To explore the driving problems associated with Parkinson's disease (PD) and to ascertain whether any clinical features or tests predict driver safety. METHODS: The driving ability of 154 individuals with PD referred to a driving assessment centre was determined by a combination of clinical tests, reaction times on a test rig and an in-car driving test. RESULTS: The majority of cases (104, 66%) were able to continue driving although 46 individuals required an automatic transmission and 10 others needed car modifications. Ability to drive was predicted by the severity of physical disease, age, presence of other associated medical conditions, particularly dementia, duration of disease, brake reaction, time on a test rig and score on a driving test (all p<0.001). The level of drug treatment and the length of driving history were not correlated. Discriminant analysis revealed that the most important features in distinguishing safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction time, moderate disease associated with another medical condition and high score on car testing. CONCLUSIONS: Most individuals with PD are safe to drive, although many benefit from car modifications or from using an automatic transmission. A combination of clinical tests and in-car driving assessment will establish safety to drive, and a number of clinical correlates can be shown to predict the likely outcome and may assist in the decision process. This is the largest series of consecutive patients seen at a driving assessment centre reported to date, and the first to devise a scoring system for on-road driving assessment.

During 1994-2005, we isolated Mycobacterium microti from 5 animals and 4 humans. Only 1 person was immunocompromised. Spoligotyping showed 3 patterns: vole type, llama type, and a new variant llama type.

The outcomes of the Follett Committee report are described and the question of access to research collections is discussed. The considerations of a national research strategy and the work of Professor Anderson’s committee are considered, and the importance of the Coopers and Lybrand study of levels and costs of use of higher education libraries by external researchers emphasised. The development of a strategy for research access is described including demonstrator projects and non‐formula funding for cataloguing, preservation and improved access to major humanities collections. The impact of electronic informations and wider developments is also discussed.

Devising Consumption explores the vital role played by thefinancial service industries in enabling the poor to consumeover the last hundred and fifty years. Spending requiresmeans, but these industries also offered practical marketingdevices that captured, captivated and enticed poorconsumers. The role of these devices has been poorlyunderstood both in the social sciences and in businessstudies and marketing. The book advances the case for a morepragmatic understanding of how ordinary, dull, everydayconsumption is arranged, and offers an alternative toorthodox approaches.

OBJECTIVES: (A) To examine the prevalence and demographic characteristics of hepatitis C virus (HCV) infection among childbearing women in Scotland; and (B) to determine the extent of maternal HCV infection diagnosed prior to birth. METHODS: (A) Residual dried blood spot samples from routine neonatal screening, collected throughout Scotland during March-October 2000, were unlinked from identifiers and tested anonymously for HCV antibodies; and (B) electronic record linkage of Scotland's databases of births and diagnosed HCV infections was performed. RESULTS: (A) Of 30,259 samples, 121 were enzyme linked immunosorbent assay repeat reactive and 88 of these were confirmed as anti-HCV positive in the recombinant immunoblot assay, representing a seroprevalence of 0.29-0.40%. HCV seroprevalence was high among 25-29 year olds (0.4-0.57%), in high deprivation areas (0.92-1.07%), and in Greater Glasgow (0.83-0.96%) and Grampian (0.38-0.62%). Adjusted relative risk for HCV infection was highest among residents in high deprivation areas of Glasgow (7.2 (95% confidence interval 2.0-25.5)). (B) Of 121 HCV infections found among women at delivery, 24% and 46% were estimated to have been diagnosed prior to pregnancy and birth, respectively. CONCLUSIONS: HCV prevalence among Scottish childbearing women is consistent with that expected from injecting drug use. Based on reported rates of mother to child transmission, 8-11 paediatric infections are expected per annum. Diagnosis in only 24% of infected women prior to pregnancy indicates the extent to which HCV goes unrecognised in the injecting community. The current HCV screening approach-to test only those with a history of injecting drug use (or other risk factors for infection)-identifies approximately a quarter of previously undetected infections among pregnant women.

Abstract Handwritten Text Recognition (HTR) technology is now a mature machine learning tool, becoming integrated in the digitisation processes of libraries and archives, speeding up the transcription of primary sources and facilitating full text searching and analysis of historic texts at scale. However, research into how HTR is changing our information environment is scant. This paper presents a systematic literature review regarding how researchers are using one particular HTR platform, Transkribus, to indicate the domains where HTR is applied, the approach taken, and how the technology is understood. 381 papers from 2015 to 2020 were gathered from Google Scholar, Scopus, and Web of Science, then grouped and coded into categories using quantitative and qualitative approaches. Published research that mentions Transkribus is international and rapidly growing. Transkribus features primarily in archival and library science publications, while a long tail of broad and eclectic disciplines, including history, computer science, citizen science, law and education, demonstrate the wider applicability of the tool. The most common paper categories were humanities applications (67%), technological (25%), users (5%) and tutorials (3%) . This paper presents the first overarching review of HTR as featured in published research, while also elucidating how HTR is affecting the information environment.

In this paper, the authors conceptualize Open Data ecosystems by analysing the major stakeholders in the UK. The conceptualization is based on a review of popular Open Data definitions and business ecosystem theories, which are applied to qualitative empirical data. The work is informed by a combination of discourse analysis and a content analysis of in-depth interviews, undertaken during the summer of 2013. Drawing on the UK as a best practice example, the authors examine a set of structural business ecosystem properties: circular flow of resources, sustainability, demand that encourages supply, and dependence developing between suppliers, intermediaries, and users. The authors identify that gaps and shortcomings remain. Most prominently, demand is not yet fully encouraging supply and actors have yet to experience fully mutual interdependence.

The World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms.

From low-obscure Beginnings raysde to Fame': critical and historical contexts of the Lord Mayor's Show 1 2 'Our devices for that solemne and Iouiall daye': the writers, the artifi cers and the livery companies 53 3 'A day of well Compos'd Variety of Speach and shew': bringing the Shows to life 4 'A briefe narration of each seuerall shew': the Show from street to print 5 'To prune and dresse the Tree of Gouernment': political and contemporary contexts of the Shows Appendices: 1 The Lord Mayors' Shows, 1585-1639: summary 2 Governance of the City of London

This paper, which is published in two parts, explores the interrelationships between nuptiality, marital fertility, and migration in Scotland during the later nineteenth and early twentieth centuries. In Part I the pervasiveness and persistence of the differences between demographic experiences in Scotland and England is explored. Though overall fertility was roughly the same, across most of the country nuptiality was significantly lower in Scotland than in England, and marital fertility was markedly higher. Population growth in Scotland was slower mainly because loss of population through migration was so widespread. Within Scotland, regional contrasts were very apparent and these are shown at parish level by maps of population change for 1861–1911, of population loss through migration for 1861–1871, and of I m and I g for years centred on 1881, 1901, and 1911. In Part II of the paper (to be published in the next issue), explanations are offered for these regional differences and also for the marked contrasts between the demographic experiences of England and Scotland in this period.

Due to an increase in bovine tuberculosis in cattle in the United Kingdom, we investigated the characteristics of Mycobacterium bovis infection in humans and assessed whether extensive transmission of M. bovis between humans has occurred. A cross-sectional study linking demographic, clinical, and DNA fingerprinting (using 15-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat [MIRU-VNTR] typing) data on cases reported between 2005 and 2008 was undertaken. A total of 129 cases of M. bovis infection in humans were reported over the period, with a decrease in annual incidence from 0.065 to 0.047 cases per 100,000 persons. Most patients were born pre-1960, before widespread pasteurization was introduced (73%), were of white ethnicity (83%), and were born in the United Kingdom (76%). A total of 102 patients (79%) had MIRU-VNTR typing data. A total of 31 of 69 complete MIRU-VNTR profiles formed eight distinct clusters. The overall clustering proportion determined using the n - 1 method was 33%. The largest cluster, comprising 12 cases, was indistinguishable from a previously reported West Midlands outbreak strain cluster and included those cases. This cluster was heterogeneous, having characteristics supporting recent zoonotic and human-to-human transmission as well as reactivation of latent disease. Seven other, smaller clusters identified had demographics supporting recrudescence rather than recent infection. A total of 33 patients had incomplete MIRU-VNTR profiles, of which 11 may have yielded 2 to 6 further small clusters if typed to completion. The incidence of M. bovis in humans in the United Kingdom remains low, and the epidemiology is predominantly that of reactivated disease.

In Part I of this paper (published in the previous issue) we outlined the major contrasts in demographic experience between almost all areas of Scotland and most of England during the later nineteenth and early twentieth centuries. We also demonstrated the existence of significant regional differences within Scotland. In Part II, interpretations are offered for these various contrasts in experience. Four Scottish regional case studies are examined, each of which shows a different combination of nuptiality, marital fertility and out-migration. In studying each case, stress is laid on the ways in which the prevailing demographic regime, if it is examined as an interrelated whole, can be seen as involving highly appropriate adjustments to the ecological, economic, and institutional contexts of the region. In this approach, ‘innovation’ aspects of the fertility decline are therefore played down; instead, for some parts of the country in particular, continued very high fertility among those who married is seen as a highly rational response to particular local social and economic situations which also encouraged very low nuptiality, and moderate or high levels of out-migration. The much lower nuptiality in Scotland compared to England is explained in part by reference to constraints on access to housing and the very limited availability of any support from the Poor Law, and in part through limited economic opportunities in a more slowly growing economy.

Purpose To examine how the synergy of open access and open source have been used at Edinburgh University Library to design and implement an e‐thesis service, and to offer a comfortable theoretical framework to aid others. Design/methodology/approach The concepts of open access and open source are introduced and compared to show the conceptual relationship between them and the natural partnering of these approaches to information freedom. The development of the open access repository (Edinburgh Research Archive, ERA) and the related open source software (Tapir for DSpace) are then examined as an opportunity for other implementers and developers to gain insight, both technical and non‐technical. Findings That open access and open source are a natural and forward looking way to develop e‐theses and other research material repositories. The discussion of developing open source and the brief study of the creation of ERA show us that this approach is both warranted and useful. Research limitations/implications It shows how institutions can leverage open source technology successfully, and further consideration must be given to this development methodology. Practical implications Software and documentation outcomes available for the community have been produced should aid the further research in this area and provide a good starting point for institutions. Originality/value We discuss for the first time both the theoretical aspects and the practical considerations surrounding an e‐theses archive which is of value to any group of information professionals considering similar activities.

Charles Darwin's publisher John Murray played an important, if often underrated, role in bringing his theories to the public. As their letters and publishing archives show they had a friendly, business like and successful relationship. This was despite fundamental scientific and religious differences between the men. In addition to publishing Darwin, Murray also published many of the critical and supportive works and reviews which Darwin's own works excited.

With a mass digitisation programme underway and the addition of non-print legal deposit and web archive collections, the National Library of Scotland is now both producing and collecting data at an unprecedented rate, with over 5PB of storage in the Library’s data centres. As well as the opportunities to support large scale analysis of the collections, this also presents new challenges around data management, storage, rights, formats, skills and access. Furthermore, by assuming the role of both creators and collectors, libraries face broader questions about the concepts of ‘collections' and ‘heritage', and the ethical implications of collecting practices. While the ‘collections as data’ movement has encouraged cultural heritage organisations to present collections in machine-readable formats, new services, processes and tools also need to be established to enable these emerging forms of research, and new modes of working need to be established to take into account an increasing need for transparency around the creation and presentation of digital collections. This commentary explores the National Library of Scotland's new digital scholarship service, the implications of this new activity and the obstacles that libraries encounter when navigating a world of Big Data.

It can be argued that institutional repositories have not had the impact (Lynch 2003, Salo 2008), initially expected, on academic scholarly communications (the exception being in a few well-developed and successful instances). So why should data repositories expect to fare any better? Firstly, data repositories can learn from publication repositories experiences and their efforts to engage researchers to accept and use these new institutional services. Secondly, they provide a technical infrastructure for storing and sharing data with the potential for providing access to complimentary research support facilities. Finally, due to the interdisciplinary expertise required to develop and maintain such systems, stronger ties will be forged between libraries, information and computing services, and researchers which will assist innovation and help to make them sustainable and embedded within academic institutional policy. This paper, whilst aware of the diverse nature of institutional and departmental practices, aims to highlight a number of initiatives that will show how research data repository infrastructures can be effectively realised through collaboration and sharing of expertise. We argue that by employing agile community, strategic and policy judgment a robust data repository infrastructure will be part of an integrated solution to effectively manage institutional research data assets.