High-resolution array CGH clarifies events occurring on 8p in carcinogenesis.

BACKGROUND: Rearrangement of the short arm of chromosome 8 (8p) is very common in epithelial cancers such as breast cancer. Usually there is an unbalanced translocation breakpoint in 8p12 (29.7 Mb - 38.5 Mb) with loss of distal 8p, sometimes with proximal amplification of 8p11-12. Rearrangements in 8p11-12 have been investigated using high-resolution array CGH, but the first 30 Mb of 8p are less well characterised, although this region contains several proposed tumour suppressor genes. METHODS: We analysed the whole of 8p by array CGH at tiling-path BAC resolution in 32 breast and six pancreatic cancer cell lines. Regions of recurrent rearrangement distal to 8p12 were further characterised, using regional fosmid arrays. FISH, and quantitative RT-PCR on over 60 breast tumours validated the existence of similar events in primary material. RESULTS: We confirmed that 8p is usually lost up to at least 30 Mb, but a few lines showed focal loss or copy number steps within this region. Three regions showed rearrangements common to at least two cases: two regions of recurrent loss and one region of amplification. Loss within 8p23.3 (0 Mb - 2.2 Mb) was found in six cell lines. Of the genes always affected, ARHGEF10 showed a point mutation of the remaining normal copies in the DU4475 cell line. Deletions within 12.7 Mb - 19.1 Mb in 8p22, in two cases, affected TUSC3. A novel amplicon was found within 8p21.3 (19.1 Mb - 23.4 Mb) in two lines and one of 98 tumours. CONCLUSION: The pattern of rearrangements seen on 8p may be a consequence of the high density of potential targets on this chromosome arm, and ARHGEF10 may be a new candidate tumour suppressor gene

Corporate Social Responsibility and Islamic Financial Institutions (IFIs): Management Perceptions from IFIs in Bahrain

Islamic finance is gaining greater attention in the finance industry, and this paper analyses how Islamic financial institutions (IFIs) are responding to the welfare needs of society. Using interview data with managers and content analysis of the disclosures, this study attempts to understand management perceptions of corporate social responsibility (CSR) in IFIs. A thorough understanding of CSR by managers, as evident in the interviews, has not been translated fully into practice. The partial use of IFIs’ potential role in social welfare would add further challenges in the era of financialisation

Методи оцінки ризиків в інформаційній системі аналізу екологічного стану басейну малої ріки

В інформаційній системі аналізу стану басейну малої ріки запропоновано методи оцінки ризиків на основі імовірнісних та статистичних оцінок, формалізації моделі гри з природою, прогнозування процесів підтоплення земель з використанням ланцюгів Маркова, розглянуто багато критеріальні моделі ризиків.In informational and analytical system of the small rivers’ ecological condition estimation the methods of risks modelling on the basis of likelihood and statistical estimations, formalization of models of game with nature, risk modelling and forecasting processes flooded lands using Markov chains are offered, multicriteria models of risks are considered

Mio-Pliocene Faunal Exchanges and African Biogeography: The Record of Fossil Bovids

The development of the Ethiopian biogeographic realm since the late Miocene is here explored with the presentation and review of fossil evidence from eastern Africa. Prostrepsiceros cf. vinayaki and an unknown species of possible caprin affinity are described from the hominid-bearing Asa Koma and Kuseralee Members (∼5.7 and ∼5.2 Ma) of the Middle Awash, Ethiopia. The Middle Awash Prostrepsiceros cf. vinayaki constitutes the first record of this taxon from Africa, previously known from the Siwaliks and Arabia. The possible caprin joins a number of isolated records of caprin or caprin-like taxa recorded, but poorly understood, from the late Neogene of Africa. The identification of these two taxa from the Middle Awash prompts an overdue review of fossil bovids from the sub-Saharan African record that demonstrate Eurasian affinities, including the reduncin Kobus porrecticornis, and species of Tragoportax. The fossil bovid record provides evidence for greater biological continuity between Africa and Eurasia in the late Miocene and earliest Pliocene than is found later in time. In contrast, the early Pliocene (after 5 Ma) saw the loss of any significant proportions of Eurasian-related taxa, and the continental dominance of African-endemic taxa and lineages, a pattern that continues today

Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the β common receptor (βCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast βCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

Travelling Waves of a Delayed SIR Epidemic Model with Nonlinear Incidence Rate and Spatial Diffusion

This paper is concerned with the existence of travlelling waves to a SIR epidemic model with nonlinear incidence rate, spatial diffusion and time delay. By analyzing the corresponding characteristic equations, the local stability of a disease-free steady state and an endemic steady state to this system under homogeneous Neumann boundary conditions is discussed. By using the cross iteration method and the Schauder's fixed point theorem, we reduce the existence of travelling waves to the existence of a pair of upper-lower solutions. By constructing a pair of upper-lower solutions, we derive the existence of a travelling wave connecting the disease-free steady state and the endemic steady state. Numerical simulations are carried out to illustrate the main results

Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes

Purpose: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits.Design: Cross-sectional study.Methods: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR).Results: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (rg=-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (rg ≥0.45; p≤3.0E-04) and between CDR and POAG were high (rg =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (rg range: -0.18 - 0.11) and non-significant (p≥0.07).Conclusion: These analyses suggest there is limited genetic correlation between diabetes- and glaucoma-related traits

Walk-ins seeking treatment at an emergency department or general practitioner out-of-hours service: a cross-sectional comparison

Background Emergency Departments (ED) in Switzerland are faced with increasing numbers of patients seeking non-urgent treatment. The high rate of walks-ins with conditions that may be treated in primary care has led to suggestions that those patients would best cared for in a community setting rather than in a hospital. Efficient reorganisation of emergency care tailored to patients needs requires information on the patient populations using the various emergency services currently available. The aim of this study is to evaluate the differences between the characteristics of walk-in patients seeking treatment at an ED and those of patients who use traditional out-of-hours GP (General Practitioner) services provided by a GP-Cooperative (GP-C). Methods In 2007 and 2009 data was collected covering all consecutive patient-doctor encounters at the ED of a hospital and all those occurring as a result of contacting a GP-C over two evaluation periods of one month each. Comparison was made between a GP-C and the ED of the Waid City Hospital in Zurich. Patient characteristics, time and source of referral, diagnostic interventions and mode of discharge were evaluated. Medical problems were classified according to the International Classification of Primary Care (ICPC-2). Patient characteristics were compared using non-parametric tests and multiple logistic regression analysis was applied to investigate independent determinants for contacting a GP-C or an ED. Results Overall a total of 2974 patient encounters were recorded. 1901 encounters were walk-ins and underwent further analysis (ED 1133, GP-C 768). Patients consulting the GP-C were significantly older (58.9 vs. 43.8 years), more often female (63.5 vs. 46.9%) and presented with non-injury related medical problems (93 vs. 55.6%) in comparison with patients at the ED. Independent determining factors for ED consultation were injury, male gender and younger age. Walk-in distribution in both settings was equal over a period of 24 hours and most common during daytime hours (65%). Outpatient care was predominant in both settings but significantly more so at the GP-C (79.9 vs. 85.7%). Conclusions We observed substantial differences between the two emergency settings in a non gate-keeping health care system. Knowledge of the distribution of diagnoses, their therapy, of diagnostic measures and of the factors which determine the patients' choice of the ED or the GP-C is essential for the efficient allocation of resources and the reduction of costs

Inter-rater reliability of categorical versus continuous scoring of fish vitality: does it affect the utility of the reflex action mortality predictor (RAMP) approach?

Scoring reflex responsiveness and injury of aquatic organisms has gained popularity as predictors of discard survival. Given this method relies upon the individual interpretation of scoring criteria, an evaluation of its robustness is done here to test whether protocol-instructed, multiple raters with diverse backgrounds (research scientist, technician, and student) are able to produce similar or the same reflex and injury score for one of the same flatfish (European plaice, Pleuronectes platessa) after experiencing commercial fishing stressors. Inter-rater reliability for three raters was assessed by using a 3-point categorical scale (‘absent’, ‘weak’, ‘strong’) and a tagged visual analogue continuous scale (tVAS, a 10 cm bar split in three labelled sections: 0 for ‘absent’, ‘weak’, ‘moderate’, and ‘strong’) for six reflex responses, and a 4-point scale for four injury types. Plaice (n = 304) were sampled from 17 research beam-trawl deployments during four trips. Fleiss kappa (categorical scores) and intra-class correlation coefficients (ICC, continuous scores) indicated variable inter-rater agreement by reflex type (ranging between 0.55 and 0.88, and 67% and 91% for Fleiss kappa and ICC, respectively), with least agreement among raters on extent of injury (Fleiss kappa between 0.08 and 0.27). Despite differences among raters, which did not significantly influence the relationship between impairment and predicted survival, combining categorical reflex and injury scores always produced a close relationship of such vitality indices and observed delayed mortality. The use of the continuous scale did not improve fit of these models compared with using the reflex impairment index based on categorical scores. Given these findings, we recommend using a 3-point categorical over a continuous scale. We also determined that training rather than experience of raters minimised inter-rater differences. Our results suggest that cost-efficient reflex impairment and injury scoring may be considered a robust technique to evaluate lethal stress and damage of this flatfish species on-board commercial beam-trawl vessels