Monitoring serum insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), IGF-I/IGFBP-3 molar ratio and leptin during growth hormone treatment for disordered growth

OBJECTIVE: Serum IGF-I levels are monitored during GH replacement treatment in adults with GH defi- ciency (GHD) to guide GH dose adjustment and to minimize occurrence of GH-related side-effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth. DESIGN: An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control. PATIENTS The study included 31 patients, grouped as (1) GHD (n=20) and (2) non-GHD (Turner syndrome n=7; Noonan syndrome n=4), who had not previously received GH treatment. MEASUREMENTS: Serum IGF-I, IGFBP-3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non-GHD groups. IGF-I, IGFBP-3 and the calculated IGF-I/IGFBP-3 molar ratio were expressed as SD scores using reference values from the local population. RESULTS: In the GHD group, IGF-I SDS before treatment was lower compared with the non-GHD (-5.4 ± 2.5 vs. -1.8 ± 1.0; P < 0.001). IGF-I (-1.8 SDS ± 2.2) and IGFBP-3 (-1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non-GHD group, IGF-I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP-3 (1.1 SDS ± 0.9) and IGF-I/IGFBP-3 molar ratio peaked at 6 months. In both groups, IGF-I SDS and IGF-I/IGFBP-3 during treatment correlated with the dose of GH expressed as IU/m2/week (r-values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 g/l; median after 12 months treatment 2.4 g/l; P = 0.02) but not the non-GHD (median before treatment 3.0 g/l; median after 12 months treatment 2.6 g/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02). CONCLUSIONS: The pattern of IGF-I, IGFBP-3 and their molar ratio during the first year of GH treatment differed between the GHD and non-GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose-dependent increase in serum IGF-I and IGF-I/IGFBP-3 may be associated with adverse effects, serum IGF-I and IGFBP-3 should be monitored routinely during longterm GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD

Philanthropy and Socio-economic Development:The Role of Large Indigenous Voluntary Organizations in Bridging Social Divides in Pakistan

Extant research has focused on the role of philanthropy in the socioeconomic development of western countries, but little is known about the role of indigenous voluntary organisations in bridging social divides in the developing world. To help redress this imbalance, we present findings on the motivations, strategies, methods, and impact of five large philanthropically funded voluntary organizations in Pakistan. We ask how and why such organizations are formed and gain traction to provide valuable services for large numbers of poor people in a society riddled with inequalities. Although differing considerably in their relations to markets and philanthropy, we find that success in all cases followed from commitment to Islamic philanthropy and the ideal of social inclusion, social innovation, exploitation of social capital, and scaling-up. Our contribution is to demonstrate how in developing countries philanthropy and social entrepreneurship together can play a decisive role in realizing a more just society

Path-dependent initialization of a single quantum dot exciton spin in a nanophotonic waveguide

We demonstrate a scheme for in-plane initialization of a single exciton spin in an InGaAs quantum dot (QD) coupled to a GaAs nanobeam waveguide. The chiral coupling of the QD and the optical mode of the nanobeam enables spin initialization fidelity approaching unity in magnetic field B=1 T and >0.9 without the field. We further show that this in-plane excitation scheme is independent of the incident excitation laser polarization and depends solely on the excitation direction. This scheme provides a robust in-plane spin excitation basis for a photon-mediated spin network for quantum information applications

Systematic study of heavy cluster emission from {210-226}^Ra isotopes

The half lives for various clusters lying in the cold reaction valleys of {210-226}^Ra isotopes are computed using our Coulomb and proximity potential model (CPPM). The computed half lives of 4^He and 14^C clusters from {210-226}^Ra isotopes are in good agreement with experimental data. Half lives are also computed using the Universal formula for cluster decay (UNIV) of Poenaru et al., and are found to be in agreement with CPPM values. Our study reveals the role of doubly magic 208^Pb daughter in cluster decay process. Geiger - Nuttall plots for all clusters up to 62^Fe are studied and are found to be linear with different slopes and intercepts. {12,14}^C emission from 220^Ra; 14^C emission from {222,224}^Ra; 14^C and 20^O emission from 226^Ra are found to be most favourable for measurement and this observation will serve as a guide to the future experiments.Comment: 22 pages, 6 figures; Nuclear Physics A (2012

Lorenz function of Bi2_{2}Te3_{3}/Sb2_{2}Te3_{3} superlattices

Combining first principles density functional theory and semi-classical Boltzmann transport, the anisotropic Lorenz function was studied for thermoelectric Bi$_{2}$Te$_{3}$/Sb$_{2}$Te$_{3}$ superlattices and their bulk constituents. It was found that already for the bulk materials Bi$_{2}$Te$_{3}$ and Sb$_{2}$Te$_{3}$, the Lorenz function is not a pellucid function on charge carrier concentration and temperature. For electron-doped Bi$_{2}$Te$_{3}$/Sb$_{2}$Te$_{3}$ superlattices large oscillatory deviations for the Lorenz function from the metallic limit were found even at high charge carrier concentrations. The latter can be referred to quantum well effects, which occur at distinct superlattice periods

Iron under Earth's core conditions: Liquid-state thermodynamics and high-pressure melting curve

{\em Ab initio} techniques based on density functional theory in the projector-augmented-wave implementation are used to calculate the free energy and a range of other thermodynamic properties of liquid iron at high pressures and temperatures relevant to the Earth's core. The {\em ab initio} free energy is obtained by using thermodynamic integration to calculate the change of free energy on going from a simple reference system to the {\em ab initio} system, with thermal averages computed by {\em ab initio} molecular dynamics simulation. The reference system consists of the inverse-power pair-potential model used in previous work. The liquid-state free energy is combined with the free energy of hexagonal close packed Fe calculated earlier using identical {\em ab initio} techniques to obtain the melting curve and volume and entropy of melting. Comparisons of the calculated melting properties with experimental measurement and with other recent {\em ab initio} predictions are presented. Experiment-theory comparisons are also presented for the pressures at which the solid and liquid Hugoniot curves cross the melting line, and the sound speed and Gr\"{u}neisen parameter along the Hugoniot. Additional comparisons are made with a commonly used equation of state for high-pressure/high-temperature Fe based on experimental data.Comment: 16 pages including 6 figures and 5 table

Nonreciprocal transmission and reflection of a chirally coupled quantum dot

We report strongly non-reciprocal behaviour for quantum dot exciton spins coupled to nano-photonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the propagation direction is found for a chirally-coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment

Inflammation Dynamically Regulates Steroid Hormone Metabolism and Action within Macrophages in Rheumatoid Arthritis

Rationale: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. Methods: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. Results: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11β-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11β-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17,), whilst 11β-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11β-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. Conclusions: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.<br/

Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: a comparative cross-sectional study

Background: Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population. Methods: A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016 . Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio- demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract. Findings: A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio (OR) 1.55 (95% Confidence Interval (CI) 1.12 - 2.11), p=0.05. There was no significant difference in 3 prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55-1.38), p=0.37. Mean best visual acuity was 0.59 (SD +/- 0.06) in podoconiosis cases compared to 0.44 (SD +/- 0.04) in controls, p=< 0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08-6.39), P = 0.03. Conclusions Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial