Dataset of air velocity and temperature fields inside an insulated box equipped with phase change material under several operating conditions.

This article contains a description of protocol to measure air velocity field (by Particle Image Velocimetry - PIV) and temperature field (by T-type thermocouples) in an insulated box equipped with Phase Change Material (PCM) of melting point 0 °C. The influence of various conditions was studied: i) PCM position (at sidewall and at top), ii) aspect ratio of the box (height/width ∼ 1 and 1.7), iii) ambient temperature (10 °C, 20 °C and 30 °C), iv) test product initial temperature (4 °C and 10 °C) and vi) spacing beneath the load (0 mm and 20 mm). This article is related to a published research paper, it provides the dataset of all experiments which can be useful for experimenter to understand the phenomena and for expert in numerical model to validate the developed model e.g., by Computational Fluid Dynamic.

Dataset of experimental study investigation of airflow and heat transfer in an insulated box equipped with a phase change material.

This article contains a detailed description of the experimental protocol of air velocity (by particle image velocimetry - PIV) and temperature measurement (by T-type thermocouples) in an insulated box equipped with a Phase Change Material (PCM). The study was conducted in an empty box and a loaded box with extruded polystyrene slabs (XPS) and methylcellulose slabs (test product). The measurement was conducted at the middle plane and lateral plane. This article contains a complete dataset along with the illustrated figures of conducted experiment. They lead to more understanding of phenomena inside a closed cavity with a cold source and can be useful for validating numerical models, e.g., the results computed by computational fluid dynamic.

A convolutional neural network segments yeast microscopy images with high accuracy.

The identification of cell borders ('segmentation') in microscopy images constitutes a bottleneck for large-scale experiments. For the model organism Saccharomyces cerevisiae, current segmentation methods face challenges when cells bud, crowd, or exhibit irregular features. We present a convolutional neural network (CNN) named YeaZ, the underlying training set of high-quality segmented yeast images (>10 000 cells) including mutants, stressed cells, and time courses, as well as a graphical user interface and a web application ( www.quantsysbio.com/data-and-software ) to efficiently employ, test, and expand the system. A key feature is a cell-cell boundary test which avoids the need for fluorescent markers. Our CNN is highly accurate, including for buds, and outperforms existing methods on benchmark images, indicating it transfers well to other conditions. To demonstrate how efficient large-scale image processing uncovers new biology, we analyze the geometries of ≈2200 wild-type and cyclin mutant cells and find that morphogenesis control occurs unexpectedly early and gradually.

Tracing water perturbation using NO3-, doc, particles size determination, and bacteria: A method development for karst aquifer water quality hazard assessment.

Karst systems, as well as springs, are vulnerable to water perturbation brought by infiltration. In this research, sources of water perturbations were examined. The first objective is to provide a method that can determine the origin of the water flowing in the karst outlet. The second objective is to identify the associated water quality hazards caused by the infiltration source. The method relies on these parameters: turbidity, DOC, NO3-, particle size, and bacteria (E. coli, enterococcus and total coliforms). As the method was applied during flood events, measurement of the water flow is also needed to have a basic knowledge on the hydrodynamic of the water resource. The proposed method is based on a high resolution monitoring of physico chemical parameters of the water flowing during flood events. Using this proposed method, (1) the origin of the water can be identified, (2) the type and nature of water perturbation can be described, and (3) the type of water perturbation that accompanies contaminants such as the one with anthropogenic source (e.g. NO3-) and bacterial nature can be determined. In identifying the water origin, this proposed method employed NO3- and DOC data normalization. Values are projected in the NO3-_norm = f(DOC_norm) reference frame. These are aligned to the slope. Depending on the obtained slope (α), water origin can be disclosed. If α > 1, the increase of concentration of DOC weighs more, characterizing water from surface runoff. Whereas, if α < 1, the consideration is more on the increase of NO3- concentration, characterizing water from unsaturated zone. However if α cannot be calculated because there is no evident slope, this characterizes the water already present in the system. Water originating from the surface runoff is prone to inorganic and bacterial contamination adsorbed by the particles. Identifying the type of water perturbation needing water treatment is important in managing the water resource. Hence, the evolution through time of NO3- and DOC with the particle size distribution, anthropogenic nature type of contaminant (i.e. in this study NO3-), and presence or absence of bacteria were examined. This method was applied in the springs of the Toulon, an important drinking water source of the city of Périgueux in France. This site was chosen considering the following factors: (1) its karst nature being vulnerable to infiltrations, having fractures and sinkholes; (2) its land use being influenced by the anthropogenic activities such as agriculture; and (3) its observed pronounced turbidity incidence. The first flood events of two hydrological cycles were assessed. Three water origins of the spring water and the respective water quality hazards were identified: (i) water from saturated zone with minerals, (ii) water from unsaturated zone with nitrate, and (iii) water from surface runoff with the presence of bacteria. The second and third types of water perturbation gave evidence that the Toulon springs can be contaminated. Hence, in terms of resource management, the information obtained can be used as a basis in forecasting and planning the management actions or water quality treatments needed.

Acceptability and Perceived Benefits and Risks of Public and Patient Involvement in Health Care Policy: A Delphi Survey in Belgian Stakeholders.

BACKGROUND: In systems with public health insurance, coverage decisions should reflect social values. Deliberation among stakeholders could achieve this goal, but rarely involves patients and citizens directly. OBJECTIVES: This study aimed at evaluating the acceptability, and the perceived benefits and risks, of public and patient involvement (PPI) in coverage decision making to Belgian stakeholders. METHODS: A two-round Delphi survey was conducted among all stakeholder groups. The survey was constructed on the basis of interviews with 10 key stakeholders and a review of the literature on participation models. Consensus was defined as 65% or more of the respondents agreeing with a statement and less than 15% disagreeing. Eighty stakeholders participated in both rounds. They were defined as the Delphi panel. RESULTS: Belgian stakeholders are open toward PPI in coverage decision processes. Benefits are expected to exceed risks. The preferred model for involvement is to consult citizens or patients, within the existing decision-making structures and at specific milestones in the process. Consulting citizens and patients is a higher level of involvement than merely informing them and a lower level than letting them participate actively. Consultation involves asking nonbinding advice on (parts of) the decision problem. According to the Delphi panel, the benefits of PPI could be increasing awareness among members of the general public and patients about the challenges and costs of health care, and enriched decision processes with expertise by experience from patients. Potential risks include subjectivity, insufficient resources to participate and weigh on the process, difficulties in finding effective ways to express a collective opinion, the risk of manipulation, and lobbying or power games of other stakeholders. CONCLUSIONS: PPI in coverage decision-making processes is acceptable to Belgian stakeholders, be it in different ways for different types of decisions. Benefits are expected to outweigh risks.

Fucus extract: cosmetic treatment for under-eye dark circles.

BACKGROUND: Dark circles around the eyes are a complex issue with two main possible causes, the accumulation of melanin in the skin around the eyes and the accumulation of heme resulting from blood leakage. The free heme produced in this manner is highly cytotoxic, proinflammatory and pro-oxidative. AIMS: To evaluate the effect of Fucus extract on heme oxygenase-1 (HO-1) stimulation activity, and to study its in vitro anti-inflammatory, antioxidative, and collagen stimulation activity. METHODS: The HO-1 stimulation activity was first evaluated at gene level by reverse transcriptase- polymerase chain reaction targeting specific HO-1 gene, and then followed by Western blot in protein level. The in vitro anti-inflammatory effect was measured by quantification of interleukin-8 (IL-8) level. The in vitro antioxidative activity was measured. Collagen stimulation activity was quantitatively measured by the amount of deposited collagen I in the extracellular matrix. RESULTS: Fucus extract was identified to have HO-1 stimulation activity at both gene and protein level. By stimulating this enzyme, it promotes the degradation of toxic heme to its protective catabolites (CO, Ferritin, and bilirubin) and reduces the source of dark circles. In addition, Fucus extract showed good anti-inflammatory efficacy. The strong antioxidation property of Fucus extract can reduce eye bags and wrinkles while its collagen boosting activity will potentially reduce fine lines and wrinkles. CONCLUSION: Fucus extract is a novel product that brings a quadruple approach to the treatment of under-eye dark circles.

Critical assessment of belgian reimbursement dossiers of orphan drugs.

BACKGROUND: Orphan medicinal products are designed to diagnose or treat rare diseases that are serious, life threatening or chronically debilitating and that affect 50 or fewer people in every 100 000 in the EU. In Belgium, the Drug Reimbursement Committee (DRC) evaluates reimbursement requests for orphan drugs based on multiple criteria: the therapeutic value, price and proposed reimbursement tariff; the importance of the drug in clinical practice; and the budget impact of the drug. OBJECTIVES: This study aimed to assess reimbursement dossiers of orphan drugs in Belgium and to compare them with the clinical evidence submitted to the European Medicines Agency (EMA). METHODS: A qualitative analysis examined all reimbursement dossiers of orphan drugs that were submitted in Belgium between January 2002 and June 2008. The following information was extracted from each dossier: description of the orphan drug; indication; reimbursement status; therapeutic value and needs; budget impact; and number of registered indications. For selected orphan drugs, an in-depth analysis extracted and compared information about the clinical trials, their primary endpoints and results from EMA documents (i.e. the marketing authorization application file, European public assessment report and summary of product characteristics) and the Belgian reimbursement dossiers. RESULTS: Reimbursement was awarded to the majority of orphan drugs. In addition to the official criteria, other negotiable factors, such as price adjustments, employment incentives, patient population restrictions and funding of diagnostic tests by the company, seemed to play a role in the reimbursement decision. Despite the low number of patients, randomized controlled trials were conducted for many orphan drugs. Budget-impact analyses were simplistic and did not consider the impact across multiple indications. Some differences were also observed between the clinical evidence submitted to the EMA and that submitted to the Belgian DRC. CONCLUSIONS: In addition to the official criteria, other negotiable factors, such as price adjustments and employment incentives, may play a role in Belgian reimbursement decisions of orphan drugs. Some differences have also been noted between the clinical evidence reported in EMA documents and the evidence included in Belgian reimbursement dossiers of orphan drugs. There appears to be a need for further standardization of Belgian reimbursement applications and for European cooperation in sharing clinical evidence of orphan drugs.

Development and in vitro assay of oxidative stress modifying formulations for wound healing promotion.

Often presented as metabolism byproducts, reactive oxygen species are linked to detrimental effects such as chronic wound, mutagenesis, cancer and skin ageing. However, recent in vitro and in vivo observations suggest that ROS, and mainly hydrogen peroxide, interfere with cell signaling acting like second messenger and inducing adaptive responses. This is particularly observed in skin wound healing where cells are exposed to H2O2 following injury. In this study, we developed and characterized an innovative formulation producing H2O2 at low concentrations, in order to mimic physiological inflammation phase. Then, this pro-oxidative formulation (CAM-GOx) was assayed in vitro on keratinocytes cell culture, compared to the blank formulation (CAM) and the anti-oxidative formulation (CAM-CAT) to assess whether oxidative stress was implied or not in cellular responses.

Issues surrounding orphan disease and orphan drug policies in Europe.

An orphan disease is a disease with a very low prevalence. Although there are 5000-7000 orphan diseases, only 50 orphan drugs (i.e. drugs developed to treat orphan diseases) were marketed in the EU by the end of 2008. In 2000, the EU implemented policies specifically designed to stimulate the development of orphan drugs. While decisions on orphan designation and the marketing authorization of orphan drugs are made at the EU level, decisions on drug reimbursement are made at the member state level. The specific features of orphan diseases and orphan drugs make them a high-priority issue for policy makers. The aim of this article is to identify and discuss several issues surrounding orphan disease and drug policies in Europe. The present system of orphan designation allows for drugs for non-orphan diseases to be designated as orphan drugs. The economic factors underlying orphan designation can be questioned in some cases, as a low prevalence of a certain indication does not equal a low return on investment for the drug across its indications. High-quality evidence about the clinical added value of orphan drugs is rarely available at the time of marketing authorization, due to the low number of patients. A balance must be struck between ethical and economic concerns. To this effect, there is a need to initiate a societal dialogue on this issue, to clarify what society wants and accepts in terms of ethical and economic consequences. The growing budgetary impact of orphan drugs puts pressure on drug expenditure. Indications can be extended for an orphan drug and the total prevalence across indications is not considered. Finally, cooperation needs to be fostered in the EU, particularly through a standardized approach to the creation and use of registries. These issues require further attention from researchers, policy makers, health professionals, patients, pharmaceutical companies and other stakeholders with a view to optimizing orphan disease and drug policies in Europe.

A comparative study of European rare disease and orphan drug markets.

OBJECTIVES: This article aims to compare regulatory aspects of rare disease and orphan drug markets in Belgium, France, Italy, the Netherlands, Sweden and the United Kingdom. METHODS: Information was derived from the international literature, analysis of legal texts, and a survey completed by national experts. RESULTS: These countries adopted varying approaches towards regulating rare disease and orphan drug markets and, hence, the availability, pricing and reimbursement of orphan drugs vary between countries. Strategies to keep down prices include public procurement in Sweden, profit controls in the United Kingdom, and price comparisons with other countries. To gain reimbursement, the cost-effectiveness and/or budget impact of orphan drugs is considered in some countries. Other societal considerations, such as whether the drug treats a life-threatening disease, are sometimes taken into account. CONCLUSIONS: Extensive government intervention exists in rare disease and orphan drug markets in the countries studied. Our recommendations are to define priorities for research on rare diseases and orphan drugs at the European level, to set up disease and patient registries with a view to investigating the long-term effectiveness and cost-effectiveness of orphan drugs, to assess the profitability of orphan drugs, and to take into account societal considerations when evaluating orphan drugs.

Budget impact analysis of orphan drugs in Belgium: estimates from 2008 to 2013.

OBJECTIVE: This article aims to calculate the impact of orphan drugs on the Belgian drug budget in 2008 and to forecast its impact over the following 5 years. METHOD: The 2008 budget impact was calculated by triangulating information derived from multiple Belgian data sources. The 2008-2013 budget impact analysis was based on three scenarios reflecting different levels of growth in the number of registered orphan drugs in the European Union, the number of drugs reimbursed in Belgium, and the average annual cost per patient per drug in Belgium. RESULTS: The orphan drug budget impact amounted to €66.2 million (or 5% of the Belgian hospital drug budget) in 2008. The impact would increase to €130-204 million in 2013, depending on the scenario. CONCLUSIONS: This static analysis measured orphan drug costs only, assuming that other components of health expenditure do not change over time. The analysis showed that the budget impact of orphan drugs in Belgium is substantial and rising, thereby putting pressure on total drug expenditure. Policy options to address the rising budget impact include pricing linked to return on investment, risk-sharing arrangements and re-appraisal of orphan drug status if additional indications are approved.

Effects of glycerol on human skin damaged by acute sodium lauryl sulphate treatment.

Glycerol, widely used as humectant, is known to protect against irritants and to accelerate recovery of irritated skin. However, most studies were done with topical formulations (i.e. emulsions) containing glycerol in relatively high amounts, preventing drawing conclusions from direct effects. In this study, acute chemical irritations were performed on the forearm with application of a 10% sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then, glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h. After elimination of moist excess consecutive to occlusive condition, in ambient air for 15 and 30 min, skin barrier function was investigated by dual measurement of skin hydration and transepidermal water loss (TEWL). Treatments with SLS solution under occlusion significantly increased TEWL and decreased skin hydration as assessed by capacitance measurements. The SLS irritant property was raised by the occlusion and the water barrier function as well as water content appeared impaired. Recovery with glycerol at low doses was remarkable through a mechanism that implies its hygroscopic properties and which is saturable. This precocious effect acts through skin rehydration by enhancing water-holding capacity of stratum corneum that would facilitate the late physiological repair of impaired skin barrier. Thus, glycerol appears to substitute for natural moisturizing factors that have been washed out by the detergent action of SLS, enhancing skin hydration but without restoring skin barrier function as depicted by TEWL values that remained high. Thus, irritant contact dermatitis treated with glycerol application compensate for skin dehydration, favouring physiological process to restore water barrier function of the impaired skin. Empirical use of glycerol added topical formulations onto detergent altered skin was substantiated in the present physicochemical approach.

Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate.

In skin inflammation, vascular endothelial growth factor (VEGF) and CXCL-8/IL-8 play an important role and are produced by activated keratinocytes. Extracts from Ginkgo biloba leaves (GBE), widely used in phytotherapy, have been reported to exert antioxidant and anti-inflammatory properties in the skin. We therefore evaluated the effects of GBE on the release of VEGF and CXCL8/IL-8 by normal human keratinocytes (NHKs) activated by tumor necrosis factor alpha (TNFalpha). Moreover, as we previously showed that epigallocatechin-3-gallate (EGCG) reduces VEGF and CXCL8/IL-8 secretion in TNFalpha-activated NHKs, we also tested its effect in association with GBE. Our results showed that GBE exerted a potent inhibition on VEGF and CXCL8/IL-8 levels in activated cells. In association with EGCG, GBE down-regulated VEGF and CXCL8/IL-8 levels in a cumulative manner in TNFalpha-stimulated NHKs. These results suggest that GBE, alone or in association with EGCG may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.

[Orphan diseases and orphan medicines: a Belgian and European study]. / Les maladies orphelines et les medicaments orphelins: une analyse belge et europeenne.

The objective of this study is to analyze policies concerning orphan medicines, used to treat patients suffering from a rare disease. The decisions about orphan designation and marketing authorization of orphan medicines are taken at European level, but each Member State is responsible for decisions regarding reimbursement. The European measures to encourage the development of orphan medicines, such as market exclusivity for a period of ten years, seem to be successful. However, this market exclusivity should be revised once the profitability of such medicines has clearly been demonstrated. Our study recommends the implementation of patient registries at the European level in order to describe the natural evolution of rare diseases and the efficacy of orphan medicines, the majority of which are relatively expensive. In 2008, Belgian social security services reimbursed orphan medicines for an amount of 66 million euro, accounting for more than 5% of the hospital pharmaceutical budget. The reimbursement of an orphan medicine to an individual patient is subject to multiple conditions. Our study recommends that a unique counter within the NIHDI is created which centralizes all reimbursement requests. The reimbursement of an orphan medicine must be linked to the provision of standardized information needed for a patient register. The NIHDI administration could then, in collaboration with external experts, evaluate reimbursement requests and ensure a coherent application of reimbursement criteria.

Subdaily growth patterns and organo-mineral nanostructure of the growth layers in the calcitic prisms of the shell of Concholepas concholepas Bruguière, 1789 (Gastropoda, Muricidae).

Fluorochrome marking of the gastropod Concholepas concholepas has shown that the prismatic units of the shell are built by superimposition of isochronic growth layers of about 2 mum. Fluorescent growth marks make it possible to establish the high periodicity of the cyclic biomineralization process at a standard growth rhythm of about 45 layers a day. Sulphated polysaccharides have been identified within the growth layers by using synchrotron radiation, whereas high resolution mapping enables the banding pattern of the mineral phase to be correlated with the layered distribution of polysaccharides. Atomic force microscopy has shown that the layers are made of nanograins densely packed in an organic component.

Skin contact irritation conditions the development and severity of allergic contact dermatitis.

Irritant contact dermatitis (ICD) is a frequent inflammatory skin disease induced by skin contact with low molecular weight chemicals such as haptens endowed with proinflammatory properties. Allergic contact dermatitis (ACD) is a frequent complication of ICD and is mediated by hapten-specific T cells primed in lymph nodes by skin emigrating dendritic cells. The aim of this study was to analyze the relationship between ICD and ACD to 2,4-dinitrofluorobenezene (DNFB) in C57BL/6 and BALB/C mice, which develop a severe and a moderate skin inflammation, respectively. Upon a single skin painting with DNFB, C57BL/6 developed within hours a more severe dose-dependent ICD response as compared to BALB/C mice, which was associated with enhanced upregulation of IL-1beta, IL-6, and IL-10. Skin exposure to a low dose of DNFB resulted, in both strains, in a low ICD that resolved in a few hours. Alternatively, skin painting with either an intermediate or a high DNFB concentration induced an ICD that subsequently gave rise to an ACD reaction whose intensity was proportional to the magnitude of the ICD response and was more severe in C57BL/6 mice than in BALB/C mice. In conclusion, the hapten-induced skin contact irritation conditions the development and the severity of ACD.

Photochemical behavior of a new long-chain UV absorber derived from 4-tert-butyl-4'-methoxydibenzoylmethane.

A new UV filter, the 1-(4-tert-butylphenyl)-2-decanyl-3-(4'-methoxyphenyl)-propane-1,3-dione, called C10-DBM, was prepared by grafting a 10-carbon aliphatic chain to the alpha-carbonyl position of 4-tert-butyl-4'-methoxydibenzoylmethane (BM-DBM), a well-known and often used UV filter. The UV-A absorption efficiency of organic solutions containing the new filter was tested and compared with identical solutions containing BM-DBM with or without irradiation (xenon lamp). The originality of this new filter is that its UV-A absorbance appeared during irradiation of the molecule. Although the molar absorption coefficient of C10-DBM in the UV-A domain was lower than that of BM-DBM, the solutions absorption exhibited a much more photostable behavior under irradiation. In this study, we first demonstrated that C10-DBM was a precursor of BM-DBM (enol isomer) by means of high-performance liquid chromatography followed by mass spectrometry. Indeed, we showed that the UV-A absorption of C10-DBM solutions appearing during the irradiation of the molecule was due to a Norrish-II reaction (beta-cleavage), which induced the release of the BM-DBM enol form and 1-decene. Then, we established a kinetic model for the photochemistry of C10-DBM and fitted the variation of UV absorption spectra to confirm the proposed mechanism.

Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFalpha.

In skin inflammation, vascular endothelial growth factor (VEGF) and IL-8 play an important role and are produced by activated keratinocytes. Recently, some polyphenols have been reported to exhibit antiinflammatory and antiangiogenic properties. We therefore evaluated the effects of green tea, its major component epigallocatechin-3-gallate (EGCG) and an isoflavone derived from soybean (genistein) on the release of VEGF and IL-8 by activated normal human keratinocytes (NHK). NHK cultured in defined medium were stimulated for 48 h with the proinflammatory cytokine TNFalpha with the addition or not of different concentrations of polyphenols. Levels of VEGF and IL-8 were measured in cell supernatants by enzyme-linked immunosorbent assays. The different constituents tested inhibited keratinocyte proliferation without inducing apoptosis. They reduced in a dose-dependent manner the basal release and the upregulation of VEGF in NHK. Green tea and EGCG were also potent inhibitors of IL-8 release by TNFalpha-stimulated NHK, whereas genistein exerted only minor effects. These results underline the divergent pathways involved in the downregulation of VEGF and IL-8 by polyphenols in activated keratinocytes. They also suggest that polyphenols may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.

Proposal for a new UVA protection factor: use of an in vitro model of immediate pigment darkening.

In order to define a new method for measuring UVA photoprotection, we built an in vitro immediate pigment darkening model (IPD). IPD is a photochemical reversible reaction induced by UVA on the skin. Our model consists of aqueous solutions of melanocytic compounds (dihydroxyphenylalanine/pheomelanins). Irradiation of these solutions with UVA induces an increase in their absorbance. Oxygen deprivation inhibits the solution darkening and light turn-off induces a decrease in the absorbance as observed in vivo. A UVA photoprotection parameter (PUVA) was defined using the ability of a sunscreen to inhibit the model reaction. A calibration of the reaction inhibition is realised using neutral beam attenuators. PUVA is defined as the percentage absorbance of a beam attenuator which would have the same inhibitory effect as the sunscreen tested. A correlation between PUVA and Diffey-Robson parameter is presented. The method developed here could be use as a indicative tool before human experiments.