Preterm infants have deficient monocyte and lymphocyte cytokine responses to Group B Streptococcus

Group B streptococcus GBS) is an important cause of early-and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS HKGBS) of preterm infants gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants GA, < 30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection

Reproducibility of aortic intima-media thickness in infants using edge-detection software and manual caliper measurements

Background: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Methods. Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 &mu;m (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 &mu;m (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 &mu;m (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 &mu;m (50) versus mean aIMT 563 &mu;m (49) respectively; p &lt; 0.001, mean difference 44 &mu;m, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. &copy; 2014 McCloskey et al.; licensee BioMed Central Ltd

Seasonlity of Kawasaki Disease: A global perspective

The authors are for the Kawasaki Disease Global Climate ConsortiumBACKGROUND: Understanding global seasonal patterns of Kawasaki disease (KD) may provide insight into the etiology of this vasculitis that is now the most common cause of acquired heart disease in children in developed countries worldwide. METHODS: Data from 1970-2012 from 25 countries distributed over the globe were analyzed for seasonality. The number of KD cases from each location was normalized to minimize the influence of greater numbers from certain locations. The presence of seasonal variation of KD at the individual locations was evaluated using three different tests: time series modeling, spectral analysis, and a Monte Carlo technique. RESULTS: A defined seasonal structure emerged demonstrating broad coherence in fluctuations in KD cases across the Northern Hemisphere extra-tropical latitudes. In the extra-tropical latitudes of the Northern Hemisphere, KD case numbers were highest in January through March and approximately 40% higher than in the months of lowest case numbers from August through October. Datasets were much sparser in the tropics and the Southern Hemisphere extra-tropics and statistical significance of the seasonality tests was weak, but suggested a maximum in May through June, with approximately 30% higher number of cases than in the least active months of February, March and October. The seasonal pattern in the Northern Hemisphere extra-tropics was consistent across the first and second halves of the sample period. CONCLUSION: Using the first global KD time series, analysis of sites located in the Northern Hemisphere extra-tropics revealed statistically significant and consistent seasonal fluctuations in KD case numbers with high numbers in winter and low numbers in late summer and fall. Neither the tropics nor the Southern Hemisphere extra-tropics registered a statistically significant aggregate seasonal cycle. These data suggest a seasonal exposure to a KD agent that operates over large geographic regions and is concentrated during winter months in the Northern Hemisphere extra-tropics.published_or_final_versio

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

Evolution of age and length at maturation of Alaskan salmon under size-selective harvest

Spatial and temporal trends and variation in life-history traits, including age and length at maturation, can be influenced by environmental and anthropogenic processes, including size-selective exploitation. Spawning adults in many wild Alaskan sockeye salmon populations have become shorter at a given age over the past half-century, but their age composition has not changed. These fish have been exploited by a gillnet fishery since the late 1800s that has tended to remove the larger fish. Using a rare, long-term dataset, we estimated probabilistic maturation reaction norms (PMRNs) for males and females in nine populations in two basins and correlated these changes with fishery size selection and intensity to determine whether such selection contributed to microevolutionary changes in maturation length. PMRN midpoints decreased in six of nine populations for both sexes, consistent with the harvest. These results support the hypothesis that environmental changes in the ocean (likely from competition) combined with adaptive microevolution (decreased PMRNs) have produced the observed life-history patterns. PMRNs did not decrease in all populations, and we documented differences in magnitude and consistency of size selection and exploitation rates among populations. Incorporating evolutionary considerations and tracking further changes in life-history traits can support continued sustainable exploitation and productivity in these and other exploited natural resources

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

State Estimation for Continuum Multi-Robot Systems on SE(3)

In contrast to conventional robots, accurately modeling the kinematics and statics of continuum robots is challenging due to partially unknown material properties, parasitic effects, or unknown forces acting on the continuous body. Consequentially, state estimation approaches that utilize additional sensor information to predict the shape of continuum robots have garnered significant interest. This paper presents a novel approach to state estimation for systems with multiple coupled continuum robots, which allows estimating the shape and strain variables of multiple continuum robots in an arbitrary coupled topology. Simulations and experiments demonstrate the capabilities and versatility of the proposed method, while achieving accurate and continuous estimates for the state of such systems, resulting in average end-effector errors of 3.3 mm and 5.02{\deg} depending on the sensor setup. It is further shown, that the approach offers fast computation times of below 10 ms, enabling its utilization in quasi-static real-time scenarios with average update rates of 100-200 Hz. An open-source C++ implementation of the proposed state estimation method is made publicly available to the community.Comment: 18 pages, 15 figures, submitted to IEEE Transactions on Robotic

Composition of early life leukocyte populations in preterm infants with and without late-onset sepsis

Background Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. Study design Single-centre prospective observational cohort study. Participants Infants born <30 weeks gestational age (GA). Outcome measures Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. Results Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6–26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. Conclusion Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression

Randomised controlled trial comparing daily VerSus depot vitamin D3 therapy in 0-16-year-old newly settled refugees in Western Australia over a period of 40 weeks

Vitamin D deficiency is highly prevalent in newly settled refugees in Western Australia (WA). If adherence to daily vitamin D therapy is problematic, depot therapy is a therapeutic alternative. The aim of this studywas to compare daily versus depot treatment and factors influencing the therapeutic outcome. Newly settled refugees (n = 151) with 25(OH)D levels less than 78 nmol/L were randomised to receive daily or depot vitamin D therapy with eight weekly interval follow up to 40 weeks. Biochemical and clinical parameters were collected at each visit. Generalized LinearMixedModels (GLMM) examined the longitudinal changes over time controlling for confounders including age, gender, treatment arm, season, country of refuge/origin and sun exposure score. Participants were aged 5.5 months to 16.0 years (75 males, 83 females). Both treatment groups achieved vitamin D sufficiency. The daily treatment group had significantly higher 25(OH)D levels at each visit post baseline and a higher proportion of participants with levels above 50 nmol/L at all time points. Time, treatment group, calcium and sun exposure score were significant predictors of 25(OH)D serum levels. Depot vitamin D therapy is an alternative to daily treatment in this at-risk group of children and adolescents in whom treatment adherence is problemati

Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of non-communicable diseases in adulthood, potentially mediated by chronic low-grade inflammation. Glycoprotein acetyls (GlycA) is a marker of chronic and cumulative inflammation. We investigated associations between ACEs and GlycA at different ages, in two generations of the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS: ALSPAC offspring's total ACE scores were generated for two age periods using prospectively collected data: 0-7y and 0-17y. GlycA was measured using high-resolution proton nuclear magnetic resonance at mean ages 8y, 18y, and 24y. Sample sizes ranged from: n = 5116 (8y) to n = 3085 (24y). ALSPAC mothers (n = 4634) retrospectively reported ACEs experienced before age 18y and GlycA was assessed at mean age 49y. We used multivariable linear regression to estimate associations between ACEs (total ACE score and individual ACEs) and subsequent GlycA in both samples, adjusting for key confounders. RESULTS: Mean GlycA levels were similar in offspring and mothers and over time. In offspring, there was no evidence that ACEs (total score or individual ACE) were associated with GlycA at age 8y or 18y, or 24y after adjustment for maternal age at birth and parity, maternal marital status, household occupational social class, maternal education, maternal smoking, own ethnicity, sex, and age in months. In mothers, there was evidence of a positive association between the total ACE score and GlycA at age 49y (adjusted mean difference 0.007 mmol/L; 95%CI: 0.003, 0.01). Emotional neglect was the only individual ACE associated with higher GlycA after adjusting for confounders and other ACEs. CONCLUSION: Results suggest the association between ACEs and GlycA may emerge in middle age. Future research should explore the extent to which inflammation in adulthood mediates well-documented associations between ACEs and adverse health outcomes in later life