Growth failure: 'idiopathic' only after a detailed diagnostic evaluation

The terms 'idiopathic short stature' (ISS) and 'small for gestational age' (SGA) were first used in the 1970s and 1980s. ISS described non-syndromic short children with undefined aetiology who did not have growth hormone (GH) deficiency, chromosomal defects, chronic illness, dysmorphic features or low birth weight. Despite originating in the premolecular era, ISS is still used as a diagnostic label today. The term 'SGA' was adopted by paediatric endocrinologists to describe children born with low birth weight and/or length, some of whom may experience lack of catch-up growth and present with short stature. GH treatment was approved by the FDA for short children born SGA in 2001, and by the EMA in 2003, and for the treatment of ISS in the US, but not Europe, in 2003. These approvals strengthened the terms 'SGA' and '155' as clinical entities. While clinical and hormonal diagnostic techniques remain important, it is the emergence of genetic investigations that have led to numerous molecular discoveries in both ISS and SGA subjects. The primary message of this article is that the labels ISS and SGA are not definitive diagnoses. We propose that the three disciplines of clinical evaluation, hormonal investigation and genetic sequencing should have equal status in the hierarchy of short stature assessments and should complement each other to identify the true pathogenesis in poorly growing patients.Developmen

An Atom Laser Based on Raman Transitions

In this paper we present an atom laser scheme using a Raman transition for the output coupling of atoms. A beam of thermal atoms (bosons) in a metastable atomic state $|1 >$ are pumped into a multimode atomic cavity. This cavity is coupled through spontaneous emission to a single mode of another cavity for the ground atomic state, $|2 >$. Above a certain threshold pumping rate a large number of atoms, $N_2$, builds up in this single quantum state and transitions to the ground state of the cavity become enhanced by a factor $(N_2 + 1)$. Atoms in this state are then coupled to the outside of the cavity with a Raman transition. This changes the internal state of the atom and imparts a momentum kick, allowing the atoms to leave the system.Comment: 8 pages, 4 postscript figures, uses RevTex, home page at http://online.anu.edu.au/Physics/Welcome.html (Some aspects of the exact physical model have changed from original version. Other general improvements included

The steady state quantum statistics of a non-Markovian atom laser

We present a fully quantum mechanical treatment of a single-mode atomic cavity with a pumping mechanism and an output coupling to a continuum of external modes. This system is a schematic description of an atom laser. In the dilute limit where atom-atom interactions are negligible, we have been able to solve this model without making the Born and Markov approximations. When coupling into free space, it is shown that for reasonable parameters there is a bound state which does not disperse, which means that there is no steady state. This bound state does not exist when gravity is included, and in that case the system reaches a steady state. We develop equations of motion for the two-time correlation in the presence of pumping and gravity in the output modes. We then calculate the steady-state output energy flux from the laser.Comment: 14 pages (twocloumn), 6 figure

Finite temperature scaling theory for the collapse of Bose-Einstein condensate

We show how to apply the scaling theory in an inhomogeneous system like harmonically trapped Bose condensate at finite temperatures. We calculate the temperature dependence of the critical number of particles by a scaling theory within the Hartree-Fock approximation and find that there is a dramatic increase in the critical number of particles as the condensation point is approached.Comment: Published online [6 pages, 3 figures

Association Analysis of Ten Candidate Genes in a Large Multinational Cohort of Small for Gestational Age Children and Children with Idiopathic Short Stature (NESTEGG study)

Background: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. Patients and Methods: We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. Results: We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. Conclusion:IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS

Reddening law and interstellar dust properties along Magellanic sight-lines

This study establishes that SMC, LMC and Milky Way extinction curves obey the same extinction law which depends on the 2200A bump size and one parameter, and generalizes the Cardelli, Clayton and Mathis (1989) relationship. This suggests that extinction in all three galaxies is of the same nature. The role of linear reddening laws over all the visible/UV wavelength range, particularly important in the SMC but also present in the LMC and in the Milky Way, is also highlighted and discussed.Comment: accepted for publication in Astrophysics and Space Science. 16 pages, 12 figures. Some figures are colour plot

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency

Purpose: the IGFALS gene encodes the acid-labile subunit (ALS) protein, which regulates circulating IGF-1. Human IGFALS mutations cause growth hormone insensitivity (GHI) associated with ALS, IGF-1 and IGFBP-3 deficiencies and mild to moderate postnatal growth impairment (height SDS ?2 to ?4). Prenatal growth impairment is not a recognised feature of this disorder, but heterozygous carriers may show an intermediate phenotype.Methods: we report a family of five subjects, including three children born small for gestational age, who were investigated for IGFALS gene mutations.Results: the proband, an 8.7 years female with pre- and postnatal growth failure (BW SDS ?3.04, Ht SDS ?3.86) and biochemical features of GHI, had a homozygous mutation of IGFALS, c.401T>A; p.L134Q. Her 6.1 years brother (BW SDS ?2.11, Ht SDS ?2.0) had the same homozygous IGFALS mutation. Both parents [adult height SDS ?1.76 (father) and ?1.82 (mother)] and her 2.7 years sister (BW SDS ?2.60, Ht SDS ?2.04) were heterozygous for the IGFALS mutation.Conclusion: significant phenotypic heterogeneity was observed between family members, in particular varying degrees of prenatal growth retardation were present in the three siblings, which may have contributed to the variation in the postnatal growth phenotyp