Season and vitamin D status are independently associated with glucose homeostasis in pregnancy

Background: Vitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism.Methods: This is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks' gestation) and late pregnancy (28 weeks' gestation). Season of first antenatal visit was categorised as extended winter (November–April) or extended summer (May–October). Multiple linear regression models, adjusted for confounders, were used for analysis.Results: Those who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P < 0.001). Compared to those who attended their first antenatal visit during extended summer, extended winter was associated with increased HOMA-IR in early-pregnancy (46.7%) and late pregnancy (53.7%), independent of 25OHD <30 nmol/L and confounders. Early pregnancy 25OHD <30 nmol/L and extended winter were independently associated with significantly higher fasting glucose in late pregnancy (B = 0.15 and 0.13, respectively).Conclusions: Women who attended their first antenatal visit during the months of extended winter were more likely to have raised insulin resistance in early pregnancy, which had a lasting association to 28 weeks, and was independent of 25OHD. Our novel findings imply that seasonal variation in insulin resistance may not be fully explained by differences in vitamin D status. This could reflect circannual rhythm or seasonal lifestyle behaviours, and requires further exploration.Trial registration: ISRCTN registry, ISRCTN54392969, date of registration: 22/04/2009, retrospectively registered

Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free.</p> <p>The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms.</p> <p>Results</p> <p>A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction.</p> <p>Conclusion</p> <p>In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.</p

Challenges of developing robust AI for intrapartum fetal heart rate monitoring

Background: CTG remains the only non-invasive tool available to the maternity team for continuous monitoring of fetal well-being during labour. Despite widespread use and investment in staff training, difficulty with CTG interpretation continues to be identified as a problem in cases of fetal hypoxia, which often results in permanent brain injury. Given the recent advances in AI, it is hoped that its application to CTG will offer a better, less subjective and more reliable method of CTG interpretation. Objectives: This mini-review examines the literature and discusses the impediments to the success of AI application to CTG thus far. Prior randomised control trials (RCTs) of CTG decision support systems are reviewed from technical and clinical perspectives. A selection of novel engineering approaches, not yet validated in RCTs, are also reviewed. The review presents the key challenges that need to be addressed in order to develop a robust AI tool to identify fetal distress in a timely manner so that appropriate intervention can be made. Results: The decision support systems used in three RCTs were reviewed, summarising the algorithms, the outcomes of the trials and the limitations. Preliminary work suggests that the inclusion of clinical data can improve the performance of AI-assisted CTG. Combined with newer approaches to the classification of traces, this offers promise for rewarding future development

From clinical educators to educational scholars and leaders: strategies for developing and advancing a career in health professions education

This toolbox article provides ideas and recommendations for academic and clinical educators seeking roles as educational scholars and leaders

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere

Source subtraction for the extended Very Small Array and 33-GHz source count estimates

We describe the source subtraction strategy and observations for the extended Very Small Array, a CMB interferometer operating at 33 GHz. A total of 453 sources were monitored at 33 GHz using a dedicated source subtraction baseline. 131 sources brighter than 20 mJy were directly subtracted from the VSA visibility data. Some characteristics of the subtracted sources, such as spectra and variability, are discussed. The 33-GHz source counts are estimated from a sample selected at 15 GHz. The selection of VSA fields in order to avoid bright sources introduces a bias into the observed counts. This bias is corrected and the resulting source count is estimated to be complete in the flux-density range 20-114 mJy. The 33-GHz source counts are used to calculate a correction to the VSA power spectrum for sources below the subtraction limit.Comment: 15 pages, 15 figures, submitted to MNRA