Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohort

Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10–1.30 per 10 cm increase in height, P<0.001): the risks did not differ significantly between specified glioma and meningioma. Body mass index (BMI) was also related to central nervous system tumour incidence, with a risk of about 20% per 10 kg m−2 increase in BMI (relative risk=1.17, 95% CI=1.03–1.34 per 10 kg m−2 increase in BMI, P=0.02). Smoking status, alcohol intake, socioeconomic level, parity, age at first birth, and oral contraceptive use were not associated with the risk of glioma or meningioma tumours. In conclusion, for women in the United Kingdom, the incidence of glioma or meningioma tumours increases with increasing height and increasing BMI

IL-1β Promotes TGF-β1 and IL-2 Dependent Foxp3 Expression in Regulatory T Cells

Earlier, we have shown that GM-CSF-exposed CD8α− DCs that express low levels of pro-inflammatory cytokines IL-12 and IL-1β can induce Foxp3+ Tregs leading to suppression of autoimmunity. Here, we examined the differential effects of IL-12 and IL-1β on Foxp3 expression in T cells when activated in the presence and absence of DCs. Exogenous IL-12 abolished, but IL-1β enhanced, the ability of GM-CSF-exposed tolerogenic DCs to promote Foxp3 expression. Pre-exposure of DCs to IL-1β and IL-12 had only a modest effect on Foxp3− expressing T cells; however, T cells activated in the absence of DCs but in the presence of IL-1β or IL-12 showed highly significant increase and decrease in Foxp3+ T cell frequencies respectively suggesting direct effects of these cytokines on T cells and a role for IL-1β in promoting Foxp3 expression. Importantly, purified CD4+CD25+ cells showed a significantly higher ability to maintain Foxp3 expression when activated in the presence of IL-1β. Further analyses showed that the ability of IL-1β to maintain Foxp3 expression in CD25+ T cells was dependent on TGF-β1 and IL-2 expression in Foxp3+Tregs and CD25− effectors T cells respectively. Exposure of CD4+CD25+ T cells to IL-1β enhanced their ability to suppress effector T cell response in vitro and ongoing experimental autoimmune thyroidits in vivo. These results show that IL-1β can help enhance/maintain Tregs, which may play an important role in maintaining peripheral tolerance during inflammation to prevent and/or suppress autoimmunity

Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals

BackgroundInfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.MethodsWe enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.ResultsDuring the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.ConclusionsWe found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC

Data from cryo-neutron phase change experiments with LH2 and LCH4

This dataset describes both raw and analyzed results from liquid-vapor phase change experiments with cryogenic propellants. Evaporation/condensation experiments with hydrogen and methane were conducted at the National Institute of Standards and Technology (NIST) in Gaithersburg, MD at the NIST Center for Neutron Research (NCNR). Tests were conducted in cylindrical and conical containers of various sizes and materials. Neutron imaging was used as a non-destructive visualization tool to probe inside the opaque metallic containers. Phase change (evaporation/condensation) was induced through precise control of pressure and/or temperature. Saturation points between 80 - 230 kPa were tested. Evaporation/condensation rates were determined through image processing. The motivation behind the experiments were to determine the accommodation coefficient which are inputs to kinetic models of phase change that represent the ratio of molecules that cross the liquid vapor interface. The values of the coefficients are published elsewhere and the data (images, temperature and pressure) are provided here. To the authors&apos; best knowledge, these are the first known neutron images of controlled cryogenic propellant phase change. The unique dataset contains a wealth of information on meniscus evaporation/condensation, phase change dynamics, thin film formation, capillary wicking, cryogenic heat transfer and neutron imaging statistics. The data could also be used as a benchmark for future experiments or as a dataset for model validation.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data from cryo-neutron phase change experiments with LH2 and LCH4

This dataset describes both raw and analyzed results from liquid-vapor phase change experiments with cryogenic propellants. Evaporation/condensation experiments with hydrogen and methane were conducted at the National Institute of Standards and Technology (NIST) in Gaithersburg, MD at the NIST Center for Neutron Research (NCNR). Tests were conducted in cylindrical and conical containers of various sizes and materials. Neutron imaging was used as a non-destructive visualization tool to probe inside the opaque metallic containers. Phase change (evaporation/condensation) was induced through precise control of pressure and/or temperature. Saturation points between 80 - 230 kPa were tested. Evaporation/condensation rates were determined through image processing. The motivation behind the experiments were to determine the accommodation coefficient which are inputs to kinetic models of phase change that represent the ratio of molecules that cross the liquid vapor interface. The values of the coefficients are published elsewhere and the data (images, temperature and pressure) are provided here. To the authors&apos; best knowledge, these are the first known neutron images of controlled cryogenic propellant phase change. The unique dataset contains a wealth of information on meniscus evaporation/condensation, phase change dynamics, thin film formation, capillary wicking, cryogenic heat transfer and neutron imaging statistics. The data could also be used as a benchmark for future experiments or as a dataset for model validation.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Loop Gain of the Common-Drain Colpitts Oscillator

This paper presents the derivations of the voltage transfer functions of the amplifier A, the feedback network β, and the loop gain Τ of the common-drain (CD) Colpitts oscillator, using the small-signal model of the CD Colpitts oscillator. The derivation of the characteristic equation of the CD Colpitts oscillator is presented. Using the characteristic equation, the equation for the oscillation frequency of the sinusoidal output voltage and the condition for steady-state oscillation are derived. The characteristic equation is used to obtain a plot of trajectories of the poles of the CD Colpitts oscillator by varying the MOSFET small-signal transconductance gm. The locations of the complex conjugate poles depicting starting and steady-state conditions for oscillations are also presented

Safety Analysis for Dynamic Update of Object Oriented Programs

Maintenance downtime and overheads for applying patches are major concerns for systems requiring round the clock availability. Hence, methods for carrying out dynamic updates are needed. However, correctness of the system during and after every dynamic update needs to be ensured. This paper defines two safety criteria, type consistency and isolation of process execution for dynamic software update. Updates involving one or more insertions of new classes, removals of old classes and replacements of old classes are considered. The condition for producing a type safe update schedule is defined. The parts of the program whose executions have to be isolated from process update are annotated by the user. Conditions are also provided for ensuring isolation of the update process from execution of annotated parts of the program.© IEE