Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort

Our aim was to derive reference intervals for all Sysmex XN hematology analyzer parameters. The rationale behind the study was the lack of reference intervals for the XN analyzer cell population data (CPD) and functional parameters. Fresh fasting blood samples from 18,484 participants in the Dutch Lifelines study were analyzed using two automated XN analyzers. Structured health questionnaire data were used to select a subgroup of 15,803 apparently healthy individuals for inclusion in the reference population. The Latent Abnormal Values Exclusion (LAVE) approach was used to reduce the influence of latent diseases in the reference population on the resulting reference intervals. We applied analysis of variance to judge the need for partitioning of the reference intervals by sex or age. We report reference intervals for 105 XN analyzer hematological parameters with and without applying LAVE. Sex-related partitioning was required for red blood cells, (RBC, RBC-O), hemoglobin (HGB, HGB-O), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), reticulocyte production index (RPI), and side scattered light intensity of the red blood cell population in the RET channel (RBC-Z). Partitioning for age was not warranted. Body mass index (BMI) and smoking had moderate influence on a minority of the parameters. We provide reference intervals for all Sysmex XN analyzer routine, CPD and functional parameters, using a direct approach in a large cohort in the Netherlands

Application of an original RT-PCR–ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients

The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil–epirubicin–cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28–79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection(β2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg−1) up to 35.71 ng mg−1(mean 1.18, median 0.13 ng mg−1). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r = –0.27). P53 was not linked to progesterone receptor (PR) status, S phase fraction, or MRP. Significantly greater MDR1 expression was observed in grade I tumours (P = 0.029). No relationship was observed between MDR1 and MRP. Neither MDR1 nor MRP was linked to ER or PR status. Unlike MDR1, MRP was correlated with the S phase: the greater the MRP, the lower the S phase (P = 0.006, r = –0.42). Univariate Cox analyses revealed that MDR1, MRP, p53 and S phase had no significant influence on progression-free or specific survival. A tendency suggested that the greater the p53, the shorter the progression-free survival (P = 0.076 as continuous and 0.069 as dichotomous). © 2000 Cancer Research Campaig

Multiple Environmental Stressors Induce Complex Transcriptomic Responses Indicative of Phenotypic Outcomes in Western Fence Lizard

Background The health and resilience of species in natural environments is increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors we examined the individual- and combined-stressor impacts of malaria infection, food limitation, and 2,4,6-trinitrotoluene (TNT) exposures on gene expression in livers of Western fence lizards (WFL, Sceloporus occidentalis) using custom WFL transcriptome-based microarrays. Results Computational analysis including annotation enrichment and correlation analysis identified putative functional mechanisms linking transcript expression and toxicological phenotypes. TNT exposure increased transcript expression for genes involved in erythropoiesis, potentially in response to TNT-induced anemia and/or methemoglobinemia and caused dose-specific effects on genes involved in lipid and overall energy metabolism consistent with a hormesis response of growth stimulation at low doses and adverse decreases in lizard growth at high doses. Functional enrichment results were indicative of inhibited potential for lipid mobilization and catabolism in TNT exposures which corresponded with increased inguinal fat weights and was suggestive of a decreased overall energy budget. Malaria infection elicited enriched expression of multiple immune-related functions likely corresponding to increased white blood cell (WBC) counts. Food limitation alone enriched functions related to cellular energy production and decreased expression of immune responses consistent with a decrease in WBC levels. Conclusions Despite these findings, the lizards demonstrated immune resilience to malaria infection under food limitation with transcriptional results indicating a fully competent immune response to malaria, even under bio-energetic constraints. Interestingly, both TNT and malaria individually increased transcriptional expression of immune-related genes and increased overall WBC concentrations in blood; responses that were retained in the TNT x malaria combined exposure. The results demonstrate complex and sometimes unexpected responses to multiple stressors where the lizards displayed remarkable resiliency to the stressor combinations investigated

The entrepreneurial ecosystem of cultural and creative industries in Porto: A sub-ecosystem approach

It is still a matter of dispute whether entrepreneurial ecosystem (EE) frameworks can be confined to a single industry in isolation, let alone whether such a sub-ecosystem approach can be employed in a domain that is distinct from the highgrowth industries usually scrutinised in the literature. This article seeks to apply a systemic and dynamic EE perspective to the development of cultural and creative industries (CCIs) within an urban context, with a particular focus on how urban development interacts with the sub-ecosystem of this sector over time. An in-depth case study in the city of Porto (Portugal) revealed that existing EE frameworks are well-suited to research on creative sub-ecosystems. It also enabled us to flesh out associations with other entrepreneurial activities and policy domains within the city. We highlight the prominent roles of local culture and policies when the context is resource-constrained: policy led to an upward, positive spiral that moved Porto's EE in relation to CCIs into a growth stage, during which it began to interact with, and faced resource competition from, high-tech entrepreneurship. We argue that having an integrated view of the dynamics of entrepreneurial sub-ecosystems and urban affairs can improve what is understood of productivity and causality in entrepreneurship

[CII] 158μ\mum Emission and Metallicity in PDRs

We study the effects of a metallicity variation on the thermal balance and [CII] fine-structure line strengths in interstellar photon dominated regions (PDRs). We find that a reduction in the dust-to-gas ratio and the abundance of heavy elements in the gas phase changes the heat balance of the gas in PDRs. The surface temperature of PDRs decreases as the metallicity decreases except for high density ($n>10^6$ cm$^{-3}$) clouds exposed to weak ($\chi< 100$) FUV fields where vibrational H$_2$-deexcitation heating dominates over photoelectric heating of the gas. We incorporate the metallicity dependence in our KOSMA-$\tau$ PDR model to study the metallicity dependence of [CII]/CO line ratios in low metallicity galaxies. We find that the main trend in the variation of the observed CII/CO ratio with metallicity is well reproduced by a single spherical clump, and does not necessarily require an ensemble of clumps as in the semi-analytical model presented by Bolatto et al. (1999).Comment: 16 pages, 14 figures, accepted by A&

Evolution of Structure in Late-type Spiral Galaxies I: Ionized Gas Kinematics in NGC 628

We study two dimensional Fabry-Perot interferometric observations of the nearby face-on late-type spiral galaxy, NGC 628, in order to analyse the ionized gas component of the interstellar medium. Covering the galaxy out to a radius larger than 12 kpc, and with a spatial sampling of 1.6 arcsec, we investigate the large-scale dynamics as well as feedback from individual HII regions into their surrounding medium. We study the role of gravitational perturbations along with that of external triggers which can disturb the kinematics and morphology of NGC 628. We verify the presence of an inner rapidly rotating disc-like component in NGC 628, which we interpret as caused by slow secular evolution of the large-scale spiral arms and oval structure. In combination with auxiliary data, we find indication for that gas is falling in from the outer parts towards the central regions, where a nuclear ring has formed at the location of the inner Lindblad resonance radius of an m=2 perturbation which could help build a pseudo-bulge in NGC 628. Moreover, we calculate radial profiles of the emission-line velocity dispersion which we use to study the role of feedback from individual HII regions. The mean velocity dispersion for the ionized gas (even when excluding pixels belonging to individual HII regions) is almost constant out to 12 kpc, although it varies from 14 to 20 km/s, with a steady decline in the outer parts. The current paper demonstrates a number of tools that we have developed for building a solid frame work for studying the evolution of structure in spiral galaxies using two dimensional kinematic observations.Comment: Accepted for publications in A&A. 13 pages, 7 figures, and including a calatogue of 376 HII regions with calibrated luminosities. Please find high-resolution version on http://www.astro.su.se/~kambiz/DOC/paper-N628.ps.g

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)