Hospitalisations from one to six years of age: Effects of Gestational Age and Severe Neonatal Morbidity

Background: To investigate whether the adverse infant health outcomes associated with early birth and severe neonatal morbidity (SNM) persist beyond the first year of life and impact on paediatric hospitalisations for children up to six years of age. Methods: The study population included all singleton live births, >32 weeks gestation in New South Wales, Australia in 2001-2005, with follow-up to six years of age. Birth data were probabilistically linked to hospitalisation data (n=392,964). The odds of hospitalisation, mean hospital length of stay (LOS) and costs, and cumulative LOS were evaluated by gestational age and SNM using multivariable analyses. Results: A total of 74,341 (18.9%) and 41,404 (10.5%) infants were hospitalized once and more than once, respectively. SNM was associated with increased odds of hospitalisation once (adjusted odds ratio (aOR) 1.16 [95% CI 1.10, 1.22]), and more than once (aOR 1.51 [1.42, 1.60]). Decreasing gestational age was associated with increasing odds of hospitalisation more than once from aOR 1.19 at 37-38 weeks to 1.49 at 33-34 weeks. Average LOS and costs per hospital admission were increased with SNM but not with decreasing gestational age. Cumulative LOS was significantly increased with SNM and decreasing gestational age. Conclusions: Adverse effects of SNM and early birth persist between one and six years of age. Strategies to prevent early birth and reduce SNM, and to increase health monitoring of vulnerable infants throughout childhood may help reduce paediatric hospitalisations.NHMRC, NSW Health Population Health and Health Services Gran

Retrieving landscape freeze/thaw state fromSoil Moisture Active Passive (SMAP) radar and radiometer measurements

Over one-third of the global land area undergoes a seasonal transition between predominantly frozen and non-frozen conditions each year, with the land surface freeze/thaw (FT) state a significant control on hydrological and biospheric processes over northern land areas and at high elevations. The NASA Soil Moisture Active Passive (SMAP) mission produced a daily landscape FT product at 3-km spatial resolution derived from ascending and descending orbits of SMAP high-resolution L-band (1.4 GHz) radar measurements. Following the failure of the SMAP radar in July 2015, coarser (36-km) footprint SMAP radiometer inputs were used to develop an alternative daily passive microwave freeze/thaw product. In this study, in situ observations are used to examine differences in the sensitivity of the 3-km radar versus the 36-km radiometer measurements to the landscape freeze/thaw state during the period of overlapping instrument operation. Assessment of the retrievals at high-latitude SMAP core validation sites showed excellent agreement with in situ flags, exceeding the 80% SMAP mission accuracy requirement. Similar performance was found for the radar and radiometer products using both air temperature and soil temperature derived FT reference flags. There was a tendency for SMAP thaw retrievals to lead the surface flags due to the influence of wet snow cover conditions on both the radar and radiometer signal. Comparison with other satellite derived FT products showed those derived from passive measurements (SMAP radiometer; Aquarius radiometer; Advanced Microwave Scanning Radiometer - 2) retrieved less frozen area than the active products (SMAP radar; Aquarius radar)

Cysteinyl-tRNA Deacylation Can Be Uncoupled from Protein Synthesis

Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNACys

Internal control genes for quantitative RT-PCR expression analysis in mouse osteoblasts, osteoclasts and macrophages

<p>Abstract</p> <p>Background</p> <p>Real-time quantitative RT-PCR (qPCR) is a powerful technique capable of accurately quantitating mRNA expression levels over a large dynamic range. This makes qPCR the most widely used method for studying quantitative gene expression. An important aspect of qPCR is selecting appropriate controls or normalization factors to account for any differences in starting cDNA quantities between samples during expression studies. Here, we report on the selection of a concise set of housekeeper genes for the accurate normalization of quantitative gene expression data in differentiating osteoblasts, osteoclasts and macrophages. We implemented the use of geNorm, an algorithm that determines the suitability of genes to function as housekeepers by assessing expression stabilities. We evaluated the expression stabilities of 18S, ACTB, B2M, GAPDH, HMBS and HPRT1 genes.</p> <p>Findings</p> <p>Our analyses revealed that 18S and GAPDH were regulated during osteoblast differentiation and are not suitable for use as reference genes. The most stably expressed genes in osteoblasts were ACTB, HMBS and HPRT1 and their geometric average constitutes a suitable normalization factor upon which gene expression data can be normalized. In macrophages, 18S and GAPDH were the most variable genes while HMBS and B2M were the most stably expressed genes. The geometric average of HMBS and B2M expression levels forms a suitable normalization factor to account for potential differences in starting cDNA quantities during gene expression analysis in macrophages. The expression stabilities of the six candidate reference genes in osteoclasts were, on average, more variable than that observed in macrophages but slightly less variable than those seen in osteoblasts. The two most stably expressed genes in osteoclasts were HMBS and B2M and the genes displaying the greatest levels of variability were 18S and GAPDH. Notably, 18S and GAPDH were the two most variably expressed control genes in all three cell types. The geometric average of HMBS, B2M and ACTB creates an appropriate normalization factor for gene expression studies in osteoclasts.</p> <p>Conclusion</p> <p>We have identified concise sets of genes suitable to use as normalization factors for quantitative real-time RT-PCR gene expression studies in osteoblasts, osteoclasts and macrophages.</p

Non-Equilibrium Bose-Einstein Condensates, Dynamical Scaling and Symmetric Evolution in large N Phi^4 theory

We analyze the non-equilibrium dynamics of the O(N) Phi^4 model in the large N limit and for states of large energy density. The dynamics is dramatically different when the energy density is above the top of the tree level potential V_0 than when it is below it.When the energy density is below V_0, we find that non-perturbative particle production through spinodal instabilities provides a dynamical mechanism for the Maxwell construction. The asymptotic values of the order parameter only depend on the initial energy density and all values between the minima of the tree level potential are available, the asymptotic dynamical `effective potential' is flat between the minima. When the energy density is larger than V_0, the evolution samples ergodically the broken symmetry states, as a consequence of non-perturbative particle production via parametric amplification. Furthermore, we examine the quantum dynamics of phase ordering into the broken symmetry phase and find novel scaling behavior of the correlation function. There is a crossover in the dynamical correlation length at a time scale t_s \sim \ln(1/lambda). For t < t_s the dynamical correlation length \xi(t) \propto \sqrt{t} and the evolution is dominated by spinodal instabilities, whereas for t>t_s the evolution is non-linear and dominated by the onset of non-equilibrium Bose-Einstein condensation of long-wavelength Goldstone bosons.In this regime a true scaling solution emerges with a non- perturbative anomalous scaling length dimension z=1/2 and a dynamical correlation length \xi(t) \propto (t-t_s). The equal time correlation function in this scaling regime vanishes for r>2(t-t_s) by causality. For t > t_s the equal time correlation function falls of as 1/r. A semiclassical but stochastic description emerges for time scales t > t_s.Comment: Minor improvements, to appear in Phys. Rev. D. Latex file, 48 pages, 12 .ps figure

The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication

The intracellular pathogen Brucella abortus survives and replicates inside host cells within an endoplasmic reticulum (ER)-derived replicative organelle named the “Brucella-containing vacuole” (BCV). Here, we developed a subcellular fractionation method to isolate BCVs and characterize for the first time the protein composition of its replicative niche. After identification of BCV membrane proteins by 2 dimensional (2D) gel electrophoresis and mass spectrometry, we focused on two eukaryotic proteins: the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the small GTPase Rab 2 recruited to the vacuolar membrane of Brucella. These proteins were previously described to localize on vesicular and tubular clusters (VTC) and to regulate the VTC membrane traffic between the endoplasmic reticulum (ER) and the Golgi. Inhibition of either GAPDH or Rab 2 expression by small interfering RNA strongly inhibited B. abortus replication. Consistent with this result, inhibition of other partners of GAPDH and Rab 2, such as COPI and PKC ι, reduced B. abortus replication. Furthermore, blockage of Rab 2 GTPase in a GDP-locked form also inhibited B. abortus replication. Bacteria did not fuse with the ER and instead remained in lysosomal-associated membrane vacuoles. These results reveal an essential role for GAPDH and the small GTPase Rab 2 in B. abortus virulence within host cells

T cells at the site of autoimmune inflammation show increased potential for trogocytosis

CD4+ T cells acquire membrane fragments from antigen-presenting-cells via a process termed trogocytosis. Identifying which CD4+ T cells undergo trogocytosis in co-culture with Ag-loaded APC can enrich for antigen-reactive T cells without knowledge of their fine specificity or cytokine-production profiles. We sought to assess the suitability of this method to identify disease relevant effector and regulatory T cells during autoimmune inflammation. Trogocytosis efficiently identified MBP-reactive T cells in vitro and ex-vivo following immunization. However, Foxp3+ regulatory T cells constitutively displayed a higher rate of trogocytosis than their Foxp3- counterparts which limits the potential of trogocytosis to identify antigen-reactive Treg cells. During inflammation a locally elevated rate of trogocytosis (seen in both effector and regulatory T cells isolated from the inflamed CNS) precludes the use of trogocytosis as a measure of antigenic reactivity among cells taken from inflammatory sites. Our results indicate trogocytosis detection can enrich for Ag-reactive conventional T cells in the periphery but is limited in its ability to identify Ag-reactive Treg or T effector cells at sites of inflammation. Increased trogocytosis potential at inflammatory sites also draws into the question the biological significance of this phenomenon during inflammation, in Treg mediated suppression and for the maintenance of tolerance in health and disease

The histology of ovarian cancer: worldwide distribution and implications for international survival comparisons (CONCORD-2)

Objective Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995â\u80\u932009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included. We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results During 2005â\u80\u932009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions The distribution of ovarian cancer histology varies widely worldwide. Type I epithelial, germ cell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions