Bridging the gap for future clinician‐educators

Background In contrast to the training required in the UK, opportunities for medical education training in the USA are limited. Resident‐as‐teacher programmes are typically insufficient to prepare trainees to be successful clinician‐educators, but few pursue formal education degrees. We sought to assess the need for, and feasibility of, a training pathway for subspecialty fellows in a large Department of Medicine that would prepare our trainees to become effective educators. Methods Quantitative and qualitative methods were used. Previous fellowship applicants and current programme directors were surveyed to determine the potential benefits of the programme. A pilot programme was conducted with fellows interested in education to determine the feasibility of the programme. Pilot participants were interviewed regarding the benefits that they gained from the pilot and the logistical challenges that they experienced. In contrast to the training required in the UK, opportunities for medical education training in the USA are limited Results Five highly ranked fellows would have scored our programmes higher if we offered this training pathway. Pilot participants and fellowship programme directors agreed that there is a compelling need for such a training pathway. A number of themes arose from the interviews that enabled us to build the framework for a strong programme. Discussion Our findings suggest that a clinician‐educator training pathway that draws from multiple subspecialties has the potential to improve recruitment, provide needed career counselling and skills development to trainees, and to build a community of educators that will benefit the institution. Important insights from pilot participant interviews will inform the programme design, in order to keep trainees engaged and overcome logistical challenges

16 kW Yb Fiber Amplifier Using Chirped Seed Amplification for Stimulated Brillouin Scattering Suppression

In a high power fiber amplifier, a frequency-chirped seed interrupts the coherent interaction between the laser and Stokes waves, raising the threshold for stimulated Brillouin scattering (SBS). Moving the external mirror of a vertical cavity surface-emitting diode laser 0.2 μm in 10 μs can yield a frequency chirp of 5×1017  Hz/s5×1017  Hz/s at a nearly constant output power. Opto-electronic feedback loops can linearize the chirp, and stabilize the output power. The linear variation of phase with time allows multiple amplifiers to be coherently combined using a frequency shifter to compensate for static and dynamic path length differences. The seed bandwidth, as seen by the counter-propagating SBS, also increases linearly with fiber length, resulting in a nearly-length-independent SBS threshold. Experimental results at the 1.6 kW level with a 19 m delivery fiber are presented. A numerical simulation is also presented

Wideband Electrically Pumped 1050-nm MEMS-Tunable VCSEL for Ophthalmic Imaging

In this paper, we present a 1050-nm electrically pumped microelectromechanically tunable vertical cavity surface-emitting laser (MEMS-VCSEL) with a record dynamic tuning bandwidth of 63.8 nm, suitable for swept-source optical coherence tomography (SS-OCT) imaging. These devices provide reduced cost and complexity relative to previously demonstrated optically pumped devices by obviating the need for a pump laser and associated hardware. We demonstrate ophthalmic SS-OCT imaging with the electrically-pumped MEMS-VCSEL at a 400 kHz axial scan rate for wide-field imaging of the in vivo human retina over a 12 mm × 12 mm field and for OCT angiography of the macula over 6 mm × 6 mm and 3 mm × 3 mm fields to show retinal vasculature and capillary structure near the fovea. These results demonstrate the feasibility of electrically pumped MEMS-VCSELs in ophthalmic instrumentation, the largest clinical application of OCT. In addition, we estimate that the 3 dB coherence length in air is 225 ± 51 m, far greater than required for ophthalmic SS-OCT and suggestive of other distance ranging applications.National Eye InstituteNational Institutes of Health (U.S.) (Grant R01-EY011289-28)National Institutes of Health (U.S.) (Grant R44-EY022864-02)National Institutes of Health (U.S.) (Grant R44-EY022864-03)National Institutes of Health (U.S.) (Grant R01-CA075289-17)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-12-1-0499

The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development

Recent advances in MEMS-VCSELs for high performance structural and functional SS-OCT imaging

Since the first demonstration of swept source optical coherence tomography (SS-OCT) imaging using widely tunable micro-electromechanical systems vertical cavity surface-emitting lasers (MEMS-VCSELs) in 2011, VCSEL-based SSOCT has advanced in both device and system performance. These advances include extension of MEMS-VCSEL center wavelength to both 1060nm and 1300nm, improved tuning range and tuning speed, new SS-OCT imaging modes, and demonstration of the first electrically pumped devices. Optically pumped devices have demonstrated continuous singlemode tuning range of 150nm at 1300nm and 122nm at 1060nm, representing a fractional tuning range of 11.5%, which is nearly a factor of 3 greater than the best reported MEMS-VCSEL tuning ranges prior to 2011. These tuning ranges have also been achieved with wavelength modulation rates of >500kHz, enabling >1 MHz axial scan rates. In addition, recent electrically pumped devices have exhibited 48.5nm continuous tuning range around 1060nm with 890kHz axial scan rate, representing a factor of two increase in tuning over previously reported electrically pumped MEMS-VCSELs in this wavelength range. New imaging modes enabled by optically pumped devices at 1060nm and 1300nm include full eye length imaging, pulsatile Doppler blood flow imaging, high-speed endoscopic imaging, and hand-held wide-field retinal imaging.National Institutes of Health (U.S.) (Grant R44EY022864-01)National Institutes of Health (U.S.) (Grant R44EY022864-02)National Institutes of Health (U.S.) (Grant R44CA101067-05)National Institutes of Health (U.S.) (Grant R44CA101067-06)National Institutes of Health (U.S.) (Grant R44CA101067-07)National Institutes of Health (U.S.) (Grant R01-EY011289-26)National Institutes of Health (U.S.) (Grant R01-CA075289-15)National Institutes of Health (U.S.) (Grant R01-EY013178-12)National Institutes of Health (U.S.) (Grant R01-EY013516-09)National Institutes of Health (U.S.) (Grant R01-EY018184-05)National Institutes of Health (U.S.) (Grant R01-NS057476-05)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (Grant FA9550-12-1-0499)Thorlabs, Inc

Metabolomics : population epidemiology and concordance in Australian children aged 11-12 years and their parents

Objectives Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11-12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent-child dyads. Design The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. Setting Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. Participants 1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent-child dyads (518 mother-daughter, 469 mother-son, 68 father-daughter and 78 father-son). Outcome measures 228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis. Results We identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent-child comparisons. Conclusions We describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent-child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.Peer reviewe

Cross-sectional metabolic profiles of mental health in population-based cohorts of 11-to 12-year-olds and mid-life adults: The Longitudinal Study of Australian Children

Objective:Poorer mental health in adulthood is associated with increased risk of cardiovascular disease and reduced life expectancy. However, little is known of the molecular pathways underpinning this relationship and how early in life adverse metabolite profiles relate to self-reported variation in mental health. We examined cross-sectional associations between mental health and serum metabolites indicative of cardiovascular health, in large Australian population-based cohorts at two stages of the life-course.Methods:We characterised cross-sectional serum nuclear magnetic resonance metabolite profiles of positively and negatively framed mental health in a large population-based sample of Australian 11- to 12-year-olds (n = 1172; 51% girls) and mid-life adults (n = 1322; mean age 45 years; 87% women). We examined multiple standard self-report mental health scales, spanning psychosocial health, general well-being, life satisfaction, and health-related quality of life. Linear regression was used to investigate the cross-sectional association between mental health and each metabolite (n = 73) in children and adults separately, unadjusted and adjusted for age, sex, socioeconomic position and body mass index.Results:Better child and adult mental health were associated with lower levels of the inflammatory marker glycoprotein acetyls, and a favourable, less atherogenic lipid/lipoprotein profile. Patterns of association in children were generally weaker than in adults. Associations were generally modest and partially attenuated when adjusted for body mass index.Conclusions:In general, metabolite profiles associated with better child and adult mental health closely aligned with those predictive of better cardiovascular health in adults. Our findings support previous evidence for the likely bidirectional relationship between mental health and cardiovascular disease risk, by extending this evidence base to the molecular level and in children.</div

Interactive analysis of systems biology molecular expression data

Peer reviewedPublisher PD

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS

Consortium for the Study of Pregnancy Treatments (Co-OPT) : An international birth cohort to study the effects of antenatal corticosteroids

Acknowledgments We are grateful to the Co-OPT collaborators from Finland, Iceland, Israel, Nova Scotia, and Scotland, who have provided high-quality patient data, without which the Co-OPT ACS cohort would not have been possible. We acknowledge Public Health Scotland for providing us with a secure data analytical platform in which to undertake this research and are particularly grateful to Anna Schneider who has been the data controller for this project. Co-OPT collaborators: Karel Allegaert (Belgium), Jasper Been (Netherlands), David Burgner (Australia), Sohinee Bhattacharya (UK), Kate Duhig (UK), Kristjana Einarsdóttir (Iceland), John Fahey (Canada), Lani Florian (UK), Abigail Fraser (UK), Mika Gissler (Finland), Cynthia Gyamfi-Bannerman (USA), Bo Jacobsson (Sweden), Eyal Krispin (Israel), Stefan Kuhle (Canada), Marius Lahti-Pulkkinen (Finland), Jessica Miller (Australia), Ben Mol (Australia), Sarah Murray (UK), Jane Norman (UK), Lars Henning Pedersen (Denmark), Richard Riley (UK), Devender Roberts (UK), Ewoud Schuit (Netherlands), Aziz Sheikh (UK), Ting Shi (UK), Joshua Vogel (Australia), Rachael Wood (UK), John Wright (UK), Helga Zoega (Australia). Funding Information: The Co-OPT ACS study is funded through a Wellcome Trust Clinical Career Development Fellowship grant (Funding Reference number 209560/Z/17) awarded to Sarah J Stock. The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript. The Sponsor of the study is the University of Edinburgh (www.ed.ac. uk), Sponsor reference AC19119. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD