Characteristics of children with the best and poorest first- and second-year growth during rhGH therapy: data from 25 years of the Genentech national cooperative growth study (NCGS)

Background Models assessing characteristics contributing to response to recombinant human growth hormone (rhGH) response rarely address growth extremes in both years 1 and 2 or examine how children track from year to year. Using National Cooperative Growth Study (NCGS) data, we determined characteristics contributing to responsiveness to rhGH and the pattern of change from years 1 to 2. Patients and methods Height velocity standard deviation score (HV SDS) for 2 years for prepubertal children with idiopathic GH deficiency (IGHD) (n = 1899) and idiopathic short stature (ISS) (n = 1186) treated with similar doses for two years were computed. Group 1 = HV SDS \u3c −1; 2 = HV SDS −1 to +1; 3 = HV SDS \u3e +1. Results For IGHD, mean age was 7.5 years and similar in all groups. Year 1 HV SDS was associated with greater body mass index (BMI) SDS, lower pre-treatment HV, baseline height SDS, greater target height SDS minus height SDS, and lower maximum stimulated GH (P \u3c0.0001). Year 2, 172/271 (73%) in group 1 moved to either group 2 (n = 156) or 3 (n = 16). Year 2 HV SDS was associated with greater year 1 HV SDS (r = 0.045, P \u3c0.0001), greater BMI SDS, taller parents and lower peak GH. For ISS, year 1 HV SDS was associated with greater BMI SDS and lower pre-treatment HV (P≤0.0001). 109/169 (64%) in group 1 moved to group 2 (n = 90) or group 3 (n = 19). Greater year 2 HV SDS was related to year 1 HV SDS (r = 0.27, P \u3c0.0001). Conclusion For IGHD, multiple characteristics contributed to best first-year response but for ISS, best first-year HV SDS was associated only with BMI SDS and inversely with pre-treatment HV. For both GHD and ISS, year 1 HV SDS was not a strong enough predictor of year 2 HV SDS to use first-year HV alone to determine GH continuation

Environmental conical nozzle levitator equipped with dual lasers

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Direct ink writing of ultra-high temperature ceramics

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From the atomic scale to the bulk: Ultra high temperature evaluation of metal diborides MB2 (M = Ta, Ti, Hf, Zr, Nb)

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Adult and Near-Adult Height in Patients with Severe Insulin-Like Growth Factor-I Deficiency after Long-Term Therapy with Recombinant Human Insulin-Like Growth Factor-I

BACKGROUND: Treatment with recombinant human insulin-like growth factor-I (IGF-I) stimulates linear growth in children with severe IGF-I deficiency (IGFD). AIMS: To evaluate the efficacy and safety of treatment with IGF-I in patients with severe IGFD treated until adult or near-adult height. METHODS: Twenty-one children with severe IGFD were treated until adult or near-adult height under a predominantly open-label design. All patients were naive to IGF-I. Recombinant human IGF-I was administered subcutaneously in doses between 60 and 120 µg/kg twice daily. Nine patients received additional therapy with gonadotropin- releasing hormone (GnRH) analog for a mean period of 2.9 ± 1.8 years. RESULTS: Mean duration of treatment was 10.0 years. Mean height velocity increased from 3.1 cm/year prior to treatment to 7.4 cm/year during the first year of treatment. Height velocities during the subsequent years were lower, but remained above baseline for up to 12 years. Cumulative mean Δ height SD score at (near) adult height was +2. The observed mean gain in height was 13.4 cm more than had been expected without treatment. The adult height achieved by the patients also treated with GnRH analog was not different from those who received IGF-I therapy alone. There were no new safety signals identified in these patients, a subset of those previously reported. CONCLUSION: Long-term therapy with IGF-I improves adult height of patients with severe IGFD. Most patients did not bring their heights into the normal adult range

A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE)

Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species

A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE)

Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species

Water in cratonic lithosphere : calibrating laboratory-determined models of electrical conductivity of mantle minerals using geophysical and petrological observations

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q06010, doi:10.1029/2012GC004055.Measurements of electrical conductivity of “slightly damp” mantle minerals from different laboratories are inconsistent, requiring geophysicists to make choices between them when interpreting their electrical observations. These choices lead to dramatically different conclusions about the amount of water in the mantle, resulting in conflicting conclusions regarding rheological conditions; this impacts on our understanding of mantle convection, among other processes. To attempt to reconcile these differences, we test the laboratory-derived proton conduction models by choosing the simplest petrological scenario possible – cratonic lithosphere – from two locations in southern Africa where we have the most complete knowledge. We compare and contrast the models with field observations of electrical conductivity and of the amount of water in olivine and show that none of the models for proton conduction in olivine proposed by three laboratories are consistent with the field observations. We derive statistically model parameters of the general proton conduction equation that satisfy the observations. The pre-exponent dry proton conduction term (σ0) and the activation enthalpy (ΔHwet) are derived with tight bounds, and are both within the broader 2σ errors of the different laboratory measurements. The two other terms used by the experimentalists, one to describe proton hopping (exponent r on pre-exponent water content Cw) and the other to describe H2O concentration-dependent activation enthalpy (term αCw1/3 added to the activation energy), are less well defined and further field geophysical and petrological observations are required, especially in regions of higher temperature and higher water content.The SAMTEX data were acquired through funding provided by the Continental Dynamics program of the U.S. National Science Foundation (grant EAR0455242 to RLE), the South African Department of Science and Technology (grant to South African Council for Geoscience), and Science Foundation Ireland (grant 05/RGP/GEO001 to AGJ) plus financial and/or logistical support provided by all members of the SAMTEX consortium. JF was initially supported by an IRCSET grant to AGJ for the TopoMed project (TopoMed: Plate reorganization in the western Mediterranean: Lithospheric causes and topographic consequences) within the European Science Foundation’s TOPOEUROPE EUROCORES (http://www.esf.org/activities/eurocores/ running-programmes/topo-europe.html), and subsequently by an SFI PI grant (10/IN.1/I3022) to AGJ for IRETHERM (www.iretherm.ie).2012-12-1

Velocity–conductivity relationships for mantle mineral assemblages in Archean cratonic lithosphere based on a review of laboratory data and Hashin–Shtrikman extremal bounds

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Lithos 109 (2009): 131-143, doi:10.1016/j.lithos.2008.10.014.Can mineral physics and mixing theories explain field observations of seismic velocity and electrical conductivity, and is there an advantage to combining seismological and electromagnetic techniques? These two questions are at the heart of this paper. Using phenomologically-derived state equations for individual minerals coupled with multi-phase, Hashin-Shtrikman extremal-bound theory we derive the likely shear and compressional velocities and electrical conductivity at three depths, 100 km, 150 km and 200 km, beneath the central part of the Slave craton and beneath the Kimberley region of the Kaapvaal craton based on known petrologically-observed mineral abundances and magnesium numbers, combined with estimates of temperatures and pressures. We demonstrate that there are measurable differences between the physical properties of the two lithospheres for the upper depths, primarily due to the different ambient temperature, but that differences in velocity are negligibly small at 200 km. We also show that there is an advantage to combining seismic and electromagnetic data, given that conductivity is exponentially dependent on temperature whereas the shear and bulk moduli have only a linear dependence in cratonic lithospheric rocks. Focussing on a known discontinuity between harzburgite-dominated and lherzolitic mantle in the Slave craton at a depth of about 160 km, we demonstrate that the amplitude of compressional (P) wave to shear (S) wave conversions would be very weak, and so explanations for the seismological (receiver function) observations must either appeal to effects we have not considered (perhaps anisotropy), or imply that the laboratory data require further refinement