Monitoring of dioxin levels in cow's milk in Zeeuws-Vlaanderen

In 1196/1997, the Belgian government measured dioxin levels in cow's milk from dairy farms in the neighborhood of a metal reclamation plant in Zelzate above the Belgian standard of 5 pg (i) TEQ/g of milkfat. In the same period they measured high dioxin emissions at the metal reclamation plant concerned. Predictions by the dioxin chain model in the basis of the emissions didn't exclude a exceeding of the Dutch standard of 6 pg (i) TEQ/gram milkfat for cow's milk from diary farms on the Dutch side of the border. Therefore, the Dutch government decided to start a monitoring program to measure the dioxin levels in cow's milk from two selected diary farms in the neighborhood of Sas van Gent, 5 km North-east of the metal reclamation plant, on a monthly basis. In the period October 1998 - June 2000 dioxin levels in cow's milk from these two diary farms were measured. None of the values exceeded the Dutch standard. The highest levels were measured at the start of the monitoring program; 3.0 +/- 0.2 and 5.1 +/- 0.3 pg (i)-TEQ/g milkfat, for the two farms respectively, in October 1998. During the same period, October-December 1998, the dioxin levels of consumers milk, sampled on a monthly basis were monitored. The samples were collected per region of the Netherlands (North, East, South and West). The measured dioxin levels in this period resulted in a background level of 0.5-0.8 pg (i)-TEQ/g of fat. At the end of the period, in June 2000, dioxin levels were decreased to a level round 1 pg (i) TEQ/g of fat. These values are in the same order of magnitude as the back ground level of 0.3-0.4 pg (i) TEQ/g of fat found for consumers milk in the second quarter of 2000. It can be concluded that the measures taken by the metal reclamation plant, imposed by the Belgian government, presumably have led to decreasing dioxin levels in locally produced cow's milk. Therefore, in August 2000, the monitoring program in Zeeuws Vlaanderen was discontinued.In 1996/1997 is door de Belgische overheid aangetoond dat de dioxine-gehalten in koemelk, uit de omgeving van een metaalsmelterij te Zelzate, de Belgische norm van 5 pg (i) TEQ/g melkvet overschreden. Tevens werd in die periode aangetoond dat de dioxine-emissie van de betreffende metaalsmelterij verhoogd was. Berekeningen met het ketenmodel sloten een overschrijding van de Nederlandse warenwetnorm van 6 pg (i) TEQ/g melkvet aan de Nederlandse zijde van de grens niet uit. Daarom is besloten koemelk van twee geselecteerde melkveebedrijven in de omgeving van Sas van Gent, 5 km ten noord-oosten van de metaalsmelterij, te monitoren op basis van maandgemiddelde monsters. In de periode oktober 1998-juni 2000 zijn dioxinegehalten gemeten in koemelk van deze twee melkveebedrijven. De dioxinegehalten in de monsters liggen allen beneden de warenwetnorm van 6 pg (i)-TEQ/g vet. De dioxinegehalten waren aan het begin van de meetperiode het hoogst; 3.0 +/- 0.2 en 5.1 +/- 0.3 pg (i)-TEQ/g melkvet voor respectievelijk melkveebedrijf SvG-1 en SvG-2. In dezelfde periode, oktober-december 1998, werden, in het kader van een ander deelprojekt (639102-9802), ook gehalten gemeten van maandgemiddelde consumptiemelkmonsters. De monsters zijn samengesteld per regio (Noord, Oost, Zuid en West) van Nederland. De gemeten waarden lagen in deze periode op een achtergrondniveau van 0.5-0.8 pg (i)-TEQ/g vet. Aan het eind van de periode, in juni 2000, zijn de waarden gedaald tot een niveau van rond de 1 pg (i) TEQ/g vet. Deze waarden hebben dezelfde orde van grootte als het achtergrondniveau van 03.-0.4 pg (i) TEQ/g vet in consumptiemelk bemonsterd in het tweede kwartaal van 2000. Geconcludeerd kan worden dat door de genomen maatregelen bij de metaalsmelterij, opgelegd door de Belgische overheid, de dioxineconcentraties in koemelk uit de omgeving waarschijnlijk structureel tot een waarde royaal onder de norm hebben geleid. Per augustus 2000 is dan ook, door de Inspectie Gezondheidsbescherming, Waren en Veterinaire Zaken besloten het monitoren van koemelk in de omgeving van Sas van Gent stop te zetten

Can subtle changes in gene expression be consistently detected with different microarray platforms?

Background: The comparability of gene expression data generated with different microarray platforms is still a matter of concern. Here we address the performance and the overlap in the detection of differentially expressed genes for five different microarray platforms in a challenging biological context where differences in gene expression are few and subtle. Results: Gene expression profiles in the hippocampus of five wild-type and five transgenic δC-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina, LGTC home-spotted arrays. Using a fixed false discovery rate of 10% we detected surprising differences between the number of differentially expressed genes per platform. Four genes were selected by ABI, 130 by Affymetrix, 3,051 by Agilent, 54 by Illumina, and 13 by LGTC. Two genes were found significantly differentially expressed by all platforms and the four genes identified by the ABI platform were found by at least three other platforms. Quantitative RT-PCR analysis confirmed 20 out of 28 of the genes detected by two or more platforms and 8 out of 15 of the genes detected by Agilent only. We observed improved correlations between platforms when ranking the genes based on the significance level than with a fixed statistical cut-off. We demonstrate significant overlap in the affected gene sets identified by the different platforms, although biological processes were represented by only partially overlapping sets of genes. Aberrances in GABA-ergic signalling in the transgenic mice were consistently found by all platforms. Conclusion: The different microarray platforms give partially complementary views on biological processes affected. Our data indicate that when analyzing samples with only subtle differences in gene expression the use of two different platforms might be more attractive than increasing the number of replicates. Commercial two-color platforms seem to have higher power for finding differentially expressed genes between groups with small differences in expression

Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers–reaching the frontiers of individual risk prediction

Aims: This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. / Methods and results: Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27-55]. During a median follow-up of 4.3 years (IQR 1.7-7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78-0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61-0.75). / Conclusion: This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach

Statistical decadal predictions for sea surface temperatures: a benchmark for dynamical GCM predictions

Accurate decadal climate predictions could be used to inform adaptation actions to a changing climate. The skill of such predictions from initialised dynamical global climate models (GCMs) may be assessed by comparing with predictions from statistical models which are based solely on historical observations. This paper presents two benchmark statistical models for predicting both the radiatively forced trend and internal variability of annual mean sea surface temperatures (SSTs) on a decadal timescale based on the gridded observation data set HadISST. For both statistical models, the trend related to radiative forcing is modelled using a linear regression of SST time series at each grid box on the time series of equivalent global mean atmospheric CO2 concentration. The residual internal variability is then modelled by (1) a first-order autoregressive model (AR1) and (2) a constructed analogue model (CA). From the verification of 46 retrospective forecasts with start years from 1960 to 2005, the correlation coefficient for anomaly forecasts using trend with AR1 is greater than 0.7 over parts of extra-tropical North Atlantic, the Indian Ocean and western Pacific. This is primarily related to the prediction of the forced trend. More importantly, both CA and AR1 give skillful predictions of the internal variability of SSTs in the subpolar gyre region over the far North Atlantic for lead time of 2 to 5 years, with correlation coefficients greater than 0.5. For the subpolar gyre and parts of the South Atlantic, CA is superior to AR1 for lead time of 6 to 9 years. These statistical forecasts are also compared with ensemble mean retrospective forecasts by DePreSys, an initialised GCM. DePreSys is found to outperform the statistical models over large parts of North Atlantic for lead times of 2 to 5 years and 6 to 9 years, however trend with AR1 is generally superior to DePreSys in the North Atlantic Current region, while trend with CA is superior to DePreSys in parts of South Atlantic for lead time of 6 to 9 years. These findings encourage further development of benchmark statistical decadal prediction models, and methods to combine different predictions

Models in the delivery of depression care: A systematic review of randomised and controlled intervention trials

<p>Abstract</p> <p>Background</p> <p>There is still debate as to which features, types or components of primary care interventions are associated with improved depression outcomes. Previous reviews have focused on components of collaborative care models in general practice settings. This paper aims to determine the effective components of depression care in primary care through a systematic examination of both general practice and community based intervention trials.</p> <p>Methods</p> <p>Fifty five randomised and controlled research trials which focused on adults and contained depression outcome measures were identified through PubMed, PsycInfo and the Cochrane Central Register of Controlled Trials databases. Trials were classified according to the components involved in the delivery of treatment, the type of treatment, the primary focus or setting of the study, detailed features of delivery, and the discipline of the professional providing the treatment. The primary outcome measure was significant improvement on the key depression measure.</p> <p>Results</p> <p>Components which were found to significantly predict improvement were the revision of professional roles, the provision of a case manager who provided direct feedback and delivered a psychological therapy, and an intervention that incorporated patient preferences into care. Nurse, psychologist and psychiatrist delivered care were effective, but pharmacist delivery was not. Training directed to general practitioners was significantly less successful than interventions that did not have training as the most important intervention. Community interventions were effective.</p> <p>Conclusion</p> <p>Case management is important in the provision of care in general practice. Certain community models of care (education programs) have potential while others are not successful in their current form (pharmacist monitoring).</p

Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India.

Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India.The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/refractory to infection and 3) have had past exposure to sand flies.It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locations, more precise epidemiological models can be produced. The suite of data collected can also be used to inform the national programme if supplementary vector control tools, in addition to IRS, are required to address the issues of people sleeping outside

Development of the Pulmonary Vein and the Systemic Venous Sinus: An Interactive 3D Overview

Knowledge of the normal formation of the heart is crucial for the understanding of cardiac pathologies and congenital malformations. The understanding of early cardiac development, however, is complicated because it is inseparably associated with other developmental processes such as embryonic folding, formation of the coelomic cavity, and vascular development. Because of this, it is necessary to integrate morphological and experimental analyses. Morphological insights, however, are limited by the difficulty in communication of complex 3D-processes. Most controversies, in consequence, result from differences in interpretation, rather than observation. An example of such a continuing debate is the development of the pulmonary vein and the systemic venous sinus, or “sinus venosus”. To facilitate understanding, we present a 3D study of the developing venous pole in the chicken embryo, showing our results in a novel interactive fashion, which permits the reader to form an independent opinion. We clarify how the pulmonary vein separates from a greater vascular plexus within the splanchnic mesoderm. The systemic venous sinus, in contrast, develops at the junction between the splanchnic and somatic mesoderm. We discuss our model with respect to normal formation of the heart, congenital cardiac malformations, and the phylogeny of the venous tributaries

The BMP Antagonist Follistatin-Like 1 Is Required for Skeletal and Lung Organogenesis

Follistatin-like 1 (Fstl1) is a secreted protein of the BMP inhibitor class. During development, expression of Fstl1 is already found in cleavage stage embryos and becomes gradually restricted to mesenchymal elements of most organs during subsequent development. Knock down experiments in chicken and zebrafish demonstrated a role as a BMP antagonist in early development. To investigate the role of Fstl1 during mouse development, a conditional Fstl1 KO allele as well as a Fstl1-GFP reporter mouse were created. KO mice die at birth from respiratory distress and show multiple defects in lung development. Also, skeletal development is affected. Endochondral bone development, limb patterning as well as patterning of the axial skeleton are perturbed in the absence of Fstl1. Taken together, these observations show that Fstl1 is a crucial regulator in BMP signalling during mouse development