People with type 2 diabetes mellitus experience an increased prevalence of non-alcoholic fatty liver disease (NAFLD) compared with the general population and often with worse outcomes. As part of the ABCD Liraglutide Nationwide Audit Programme, we obtained and analysed data from 2009 to 2018 to assess the impact of liraglutide on alanine aminotransferase (ALT) levels as a marker of liver inflammation (often used in clinical trials as a marker of NAFLD). After excluding those with insufficient or incomplete data, we analysed the results from 1,759 patients treated in the real-world clinical setting. Our results demonstrated an overall significant decrease in median ALT (−1 U/L, 95% CI −1 to −2, p<0.001) compared with baseline, which was more pronounced in patients with elevated ALT based on gender- specific ranges (male: −4 U/L, 95% CI −3 to −6, p<0.001; female: −3 U/L, 95% CI −2 to −4, p<0.001). There was no correlation between weight loss and degree of ALT change (rho=−0.0002, p=0.41). Our data mirror outcomes from large randomised controlled trials and show that the impact of liraglutide on ALT is likely generalisable to real-world practice. Some of our data suggest that there may be a slight increase in ALT in those with normal levels at baseline, although the clinical significance of this is uncertain.

The University of Bristol, UK, holds over 33 000 pages in the Brunel Collection. This collection contains the personal papers of the Victorian engineer Isambard Kingdom Brunel, a key figure in the Industrial Revolution. However, despite its importance as a scholarly resource, no electronic catalogue of the collection exists and physical access is limited. In 2003 the University was awarded a grant carry out a pilot digitization project to bring this resource to a wider audience via the Internet. This is the first digitization project undertaken by the University Library and the process has been one of trial, error, luck and determination. The aims of providing access to a larger audience and understanding more about such a key historical figure sit alongside the technical goals of an open source, open standard, easily extensible and migratable image database and electronic catalogue. This paper describes our decisions and methods and provides a case study for the uninitiated who wish to take the plunge into digital archiving and who might learn from the paths we chose.

In the area of cultural heritage, images - photographic, scanned, or computer-generated - are often used as virtual representations of real artefacts or scenes. For these images to be authoritative, they should be a faithful representation of the original object. To interpret these images, they must be displayed. The conditions under which an image is displayed can adversely affect its appearance, so care must be taken to ensure that the user sees the end product in the way that it was intended to look. However, in digital image archiving, perceptual fidelity between the stored image and the displayed image is desirable, regardless of the medium of display or the environment in which it is exhibited, but this requires careful consideration of such diverse factors as tone and color reproduction, display device specifications and physical viewing conditions, which all contribute towards the final displayed image that the user perceives. This paper summarises the issues concerning display quality control for digital archiving.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

One hundred and fourteen kilobase pairs (kb) of contiguous genomic sequence have been determined immediately distal to the his5 genetic marker located about 0.9 Mb from the centromere on the long arm of Schizosaccharomyces pombe chromosome 2. The sequence is contained in overlapping cosmid clones c16H5, c12D12, c24C6 and c19G7, of which 20 kb are identical to previously reported sequence from clone c21H7. The remaining 93 781 bp of sequence contains 10 known genes (cdc14, cdm1, cps1, gpa1, msh2, pck2, rip1, rps30-2, sad1 and ubl1), 32 open reading frames (ORFs) capable of coding for proteins of at least 100 amino acid residues in length, one 5S rRNA gene, one tRNA(Pro) gene, one lone Tf1-type long terminal repeat (LTR) and one lone Tf2-type LTR. There is a density of one protein-coding gene per 2.2 kb and 22 of the 42 ORFs (52%) incorporate one or more introns. Twenty-one of the novel ORFs show sequence similarities which suggest functions of their products, including a cyclin C, a MADS box transcription factor, mad2-like protein, telomere binding protein, topoisomerase II-associated protein, ATP-dependent DEAH box RNA helicase, G10 protein, ubiquitin-activating e1-like enzyme, nucleoporin, prolyl-tRNA synthetase, peptidylprolyl isomerase, delta-1-pyrroline-5-carboxylate dehydrogenase, protein transport protein, coatomer epsilon, TCP-1 chaperonin, beta-subunit of 6-phosphofructokinase, aminodeoxychorismate lyase, a phosphate transport protein and a thioredoxin.

Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491 (ref. 1). The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5′ or 3′ exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.

This directory was made possible by a unique international collaboration between the 633 scientists whose names appear below. It represents both the first published description of the complete sequence of most chromsomes from Saccharomyces cerevisiae , and the first published overview of the entire sequence. As such, the authors would like future papers referring to the entire sequence and/or its contents to cite this directory; future papers referring to the sequence of individual chromosomes should refer to the papers listed at the head of page 9. The authors’ affiliations appear in the papers describing the individual chromosomes.