Development and evaluation of a multiple-locus variable-number tandem-repeats analysis assay for subtyping Salmonella Typhi strains from sub-Saharan Africa

Purpose: Molecular epidemiological investigations of the highly clonal Salmonella enterica subspecies enterica serovar Typhi (S. Typhi) are important in outbreak detection and in tracking disease transmission. In this study, we developed and evaluated a multiple-locus variable-number tandem-repeats (VNTR) analysis (MLVA) assay for characterization of S. Typhi isolates from sub-Saharan Africa. Methodology: Twelve previously reported VNTR loci were evaluated and an MLVA assay consisting of five polymorphic loci was adopted. The MLVA assay was developed for use on capillary electrophoresis systems by testing a collection of 50 S. Typhi isolates. This S. Typhi strain panel consisted of six outbreak related isolates and 44 epidemiologically unlinked isolates. Amongst these were nine S.Typhi haplotype H58 isolates. Results: The MLVA assay characterized the 50 isolates into 47 MLVA profiles while PFGE analysis of the same isolates revealed 34 pulsotypes. MLVA displayed higher discriminatory power (Simpson’s index of diversity (DI) 0.998 [95% confidence interval (CI) 0.995–1.000)] as compared to pulsed-field gel electrophoresis [Simpson’s DI 0.984 (95% CI 0.974–0.994)]. Conclusion: The MLVA assay presented in this study is a simple, rapid and more accessible tool that serves as a good alternative to other molecular subtyping methods for S. Typhi

A breaking internal wave in the surface ocean boundary layer

High-temporal resolution measurements in the Labrador Sea surface layer are presented using an upwardly profiling autonomous microstructure instrument, which captures an internal wave in the act of breaking at the base of the surface mixed layer, driving turbulence levels 2-3 orders of magnitude above the background. While lower-frequency (near-inertial) internal waves are known to be important sources of turbulence, we report here a higher-frequency internal wave breaking near the ocean surface. Due to observational limitations, the exact nature of the instability cannot be conclusively identified, but the interaction of wave-induced velocity with unresolved background shear appears to be the most likely candidate. These observations add a new process to the list of those currently being considered as potentially important for near-surface mixing. The geographical distribution and global significance of such features are unknown, and underscore the need for more extensive small-scale, rapid observations of the ocean surface layer

Screening history of women with cervical cancer: a 6-year study in Aarhus, Denmark

To identify possible weaknesses in cervical screening in Aarhus County, 10 years after the programme was introduced, screening histories were examined. A major problem for the screening programme was that 31% of women were never screened and 61% under-screened, the latter group being significantly dominated by older women and high-stage tumours

Representations of the family in postwar British amateur film: family histories in the Lane and Scrutton collection at the East Anglian Film Archive

This article examines the construction of the postwar British family in amateur film with reference to the Sidney Lane and Cecil Scrutton collection held at the East Anglian Film Archive (EAFA), particularly the films covering 1948 – 1961. Heather Norris Nicholson argues that home movies contribute to 'an understanding of leisure and visual-related practices of consumption as well as the social processes by which people came to give themselves, and others, identities' in the mid-twentieth century (Nicholson, 2004, p. 323). By considering the social and historical contexts in which these home movies were produced, and using accompanying notes by one of the filmmaker’s sons, the leisure time films of Lane and Scrutton can be analysed in order to understand how the amateur cine hobby ideologically constructed family, community and national identity in postwar Britain. The images of Christmas parties, daytrips and holidays in these films reveal much about this particular family, and are therefore very illuminating to the social historian and film scholar of today

Searching for the elusive typhoid diagnostic

Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area

Targeted sequencing of lung function loci in chronic obstructive pulmonary disease cases and controls

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; smoking is the main risk factor for COPD, but genetic factors are also relevant contributors. Genome-wide association studies (GWAS) of the lung function measures used in the diagnosis of COPD have identified a number of loci, however association signals are often broad and collectively these loci only explain a small proportion of the heritability. In order to examine the association with COPD risk of genetic variants down to low allele frequencies, to aid fine-mapping of association signals and to explain more of the missing heritability, we undertook a targeted sequencing study in 300 COPD cases and 300 smoking controls for 26 loci previously reported to be associated with lung function. We used a pooled sequencing approach, with 12 pools of 25 individuals each, enabling high depth (30x) coverage per sample to be achieved. This pooled design maximised sample size and therefore power, but led to challenges during variant-calling since sequencing error rates and minor allele frequencies for rare variants can be very similar. For this reason we employed a rigorous quality control pipeline for variant detection which included the use of 3 independent calling algorithms. In order to avoid false positive associations we also developed tests to detect variants with potential batch effects and removed them before undertaking association testing. We tested for the effects of single variants and the combined effect of rare variants within a locus. We followed up the top signals with data available (only 67% of collapsing methods signals) in 4,249 COPD cases and 11,916 smoking controls from UK Biobank. We provide suggestive evidence for the combined effect of rare variants on COPD risk in TNXB and in sliding windows within MECOM and upstream of HHIP. These findings can lead to an improved understanding of the molecular pathways involved in the development of COPD