Bioaccumulation of PCB & DDE methyl sulfones in marine mammals and their interactions with receptor proteins

PCB and DDE-Methyl sulphone metabolites are the product of enzymatic and bile acid entero hepatic metabolism in the final phase (III) of PCB and DDE detoxification in mammals following hepatic microsomal cytochrome P450-dependent metabolism (phase I) and conjugation (phase II). There is good evidence that PCB and DDE methyl sulphone (MSF) metabolites interfere with steroid binding to a receptor protein in uterine epithelium (uteroglobin - UG2 and bronchial epithelium (clara cell secretory protein - CCSP). UG and CCSP are homologous 16,000 Da proteins with different tissue-specific functions. UG binds progesterone in the pre-implantation uterus to signal localised endometrial thickening and capillary formation, vital for successful attachment of the fertilised embryo. PCB-MSFs can displace progesterone in the mammalian uterus due to their higher affinity for UG, resulting in implantation failure or early fetal death. CCSP however, functions to sequester phospholipase A2 (PLA2) released in response to stress (pathogenic infection / injury) to suppress inflammatory responses triggered by PLA2 in bronchial epithelium. CCSP is also known as retinol-binding protein (RBP) transporting retinol (vit A) to target epithelia for a functional immune response*. Studies with Harbour Seals demonstrated displacement of retinol from RBP by hydroxy-PCB metabolites resulting in immunosuppression. PCB-MSFs have been shown to accumulate in clara cells and uterine epithelium in laboratory radioactive tracer studies and CCSP-knock out studies with mice. PCB and DDE -MSFs burdens have been found in marine mammals, suggesting they may be subject to reproductive and immuno-toxic effects of these metabolites. This study determines PCB and DDE-MSFs burdens in tissues (including lung & uterus) of Harbour Seal (Phoca vitulina) and Striped Dolphin (Stenella coeruleoalba) morbillivirus victims and characterises the marine mammalian UG/CCSP protein

Alcohol Advertising over the Public Airwaves: A Study of Radio Station Managers\u27 Clearance of Alcohol-Related Advertisements

In 1996. a self-imposed ban on broadcast advertisements by the major hard liquor distillers ended. Some federally licensed broadcast outlets ended up accepting and airing advertisements for distilled liquor products such as rum and vodka while others refused. This dissertation\u27s main purpose is to study the variation found in broadcasters\u27 willingness to air alcoholic beverage commercials and to test different explanatory models for the divergence of reactions to these controversial products. In December 1997. 191 radio station general managers completed a mailed survey about their policy on alcohol advertising and specifically answered questions about what types of alcohol beverage ads they had accepted or would accept. Some would take all. The vast majority reported that they would accept such fermented alcohol products as beer and wine, but not for distilled liquor products. Others indicated that their stations refused all alcoholic beverage advertisements and would even refuse to air ads for nightclubs. An index of willingness to air alcoholic beverages and related products became the main dependent variable for the study. An analysis of the research literature suggested ethical, economic and audience factors would best account for the observed variation in station managers’ alcohol clearance decisions. Each factor was explored using statistical analysis. Stations with a religious format were unlikely to air commercials for alcohol products as were stations with a history of format stability. Younger general managers with a business-oriented educational background were the most likely to accept advertisements for alcohol-related products and businesses. However, the most powerful variable in explaining the differences in clearance of these controversial advertisements was found to be the ethical values of the manager, including his or her concern for the audience. Remarkably, the station\u27s economic and technical conditions did not have much predictive value. No strong evidence was found for a hypothesis that alcoholic beverage advertisements are price discriminated against by stations; that is. these advertisers are charged a higher price by stations because of controversial content

Determining quality of early childhood education programmes in Spaina case study

This paper presents a case study where a specific protocol for assessing the quality of education programmes for children from newborn to age three was used. The article opens with a statement of the problem and a historical overview of Spanish educational policy which suggest that one of the main purposes of current legislation (LOE, 2006) is to ensure that centres provide high quality educational experiences. The paper goes on to describe the research that has been done in order to develop a protocol designed to assess educational programmes for children from newborn through age three. Finally, the article presents the results of a pilot project in which this protocol was applied in a case study. The information gathered and the conclusions derived from two stakeholders, parents and teachers, over two academic years is analyzed

Calidad de los diagnósticos en urgencias de las lesiones por causas externas que requieren ingreso hospitalario

SummaryObjectiveTo establish the quality of emergency department diagnoses for those patients whose injuries required hospital admission.MethodsEmergency and hospital discharge diagnostics were retrieved for 339 injured patients. Severity scores (ISS) were calculated using an automatic conversion procedure (ICDMAP). Emergency diagnoses for each patient (grouped into categories) were compared with the hospital discharge ones. Quality was analyzed based on accuracy (Percy groups) and reliability (percentage of concordance) measurements. Severity scores were evaluated using reliability measures (percentage of concordance and intraclass correlation coefficient -ICC-).ResultsMean diagnoses per patient were 1.1 at the emergency department and 1.4 at hospital discharge. In the latter, there were diagnoses in each category except for those more unspecific, where there was a reduction. Overall,emergency information showed under notification. Severity scores were higher with hospital discharge data. There was a 63% percentage of concordance. When grouped into categories, severity scores had an ICC of 0.61 (moderate-good).ConclusionEmergency departments are a potential good source of information about injury severity even for those patients who require hospital admission. Emergency department injury surveillance can be very useful in assessing the magnitude and distribution of injury severity at the population level. Nevertheless for individual severity assessment, use of hospital discharge information is recommended

Learning Koopman eigenfunctions of stochastic diffusions with optimal importance sampling and ISOKANN

The dominant eigenfunctions of the Koopman operator characterize the metastabilities and slow-timescale dynamics of stochastic diffusion processes. In the context of molecular dynamics and Markov state modeling, they allow for a description of the location and frequencies of rare transitions, which are hard to obtain by direct simulation alone. In this article, we reformulate the eigenproblem in terms of the ISOKANN framework, an iterative algorithm that learns the eigenfunctions by alternating between short burst simulations and a mixture of machine learning and classical numerics, which naturally leads to a proof of convergence. We furthermore show how the intermediate iterates can be used to reduce the sampling variance by importance sampling and optimal control (enhanced sampling), as well as to select locations for further training (adaptive sampling). We demonstrate the usage of our proposed method in experiments, increasing the approximation accuracy by several orders of magnitude

The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis

Tuberculosis (TB) has been responsible for the greatest number of human deaths due to an infectious disease in general, and due to antimicrobial resistance (AMR) in particular. The etiological agents of human TB are a closely-related group of human-adapted bacteria that belong to the Mycobacterium tuberculosis complex (MTBC). Understanding how MTBC populations evolve within-host may allow for improved TB treatment and control strategies. In this Review, we highlight recent works that have shed light on how AMR evolves in MTBC populations within individual patients. We discuss the role of heteroresistance in AMR evolution, and review the bacterial, patient, and environmental factors that likely modulate the magnitude of heteroresistance within-host. We further highlight recent works on the dynamics of MTBC genetic diversity within-host, and discuss how spatial substructures in patients' lungs, spatiotemporal heterogeneity in antimicrobial concentrations, and phenotypic drug tolerance likely modulates the dynamics of MTBC genetic diversity in patients during treatment. We note the general characteristics that are shared between how the MTBC and other bacterial pathogens evolve in humans, and highlight the characteristics unique to the MTBC

Elucidating the mystery of the tripartite symbiosis plant – mycorrhizal fungi – dark septate endophytes

Non-Peer ReviewedThis study provides information on the tripartite symbiotic relationships formed by arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) in crops growing in the semiarid region of the Canadian Prairie. We found the symbiotic root systems of wheat, pea, chickpea and lentil to be morphologically distinct. The relationship between DSE and AMF abundance in roots ranged from negative in lentil to positive in wheat