Multilevel model of safety climate for furniture industries

BACKGROUND: Furniture companies can analyze their safety status using quantitative measures. However, the data needed are not always available and the number of accidents is under-reported. Safety climate scales may be an alternative. However, there are no validated Portuguese scales that account for the specific attributes of the furniture sector. OBJECTIVE: The current study aims to develop and validate an instrument that uses a multilevel structure to measure the safety climate of the Portuguese furniture industry. METHODS: The Safety Climate in Wood Industries (SCWI) model was developed and applied to the safety climate analysis using three different scales: organizational, group and individual. A multilevel exploratory factor analysis was performed to analyze the factorial structure. The studied companies’ safety conditions were also analyzed. RESULTS: Different factorial structures were found between and within levels. In general, the results show the presence of a group-level safety climate. The scores of safety climates are directly and positively related to companies’ safety conditions; the organizational scale is the one that best reflects the actual safety conditions. CONCLUSIONS: The SCWI instrument allows for the identification of different safety climates in groups that comprise the same furniture company and it seems to reflect those groups’ safety conditions. The study also demonstrates the need for a multilevel analysis of the studied instrument.

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

Multilevel model of safety climate for furniture industries

BACKGROUND: Furniture companies can analyze their safety status using quantitative measures. However, the data needed are not always available and the number of accidents is under-reported. Safety climate scales may be an alternative. However, there are no validated Portuguese scales that account for the specific attributes of the furniture sector. OBJECTIVE: The current study aims to develop and validate an instrument that uses a multilevel structure to measure the safety climate of the Portuguese furniture industry. METHODS: The Safety Climate in Wood Industries (SCWI) model was developed and applied to the safety climate analysis using three different scales: organizational, group and individual. A multilevel exploratory factor analysis was performed to analyze the factorial structure. The studied companies’ safety conditions were also analyzed. RESULTS: Different factorial structures were found between and within levels. In general, the results show the presence of a group-level safety climate. The scores of safety climates are directly and positively related to companies’ safety conditions; the organizational scale is the one that best reflects the actual safety conditions. CONCLUSIONS: The SCWI instrument allows for the identification of different safety climates in groups that comprise the same furniture company and it seems to reflect those groups’ safety conditions. The study also demonstrates the need for a multilevel analysis of the studied instrument.

Qualitative and quantitative formal model-based safety analysis : push the safety button

Magdeburg, Univ., Fak. für Informatik, Diss., 2011

Patient safety and the prevention of skin and mucosal lesions associated with airway invasive devices

AbstractOBJECTIVETo analyze the care implemented by the nursing team to promote the safety of adult patients and prevention of skin and mucosal lesions associated with the presence of lower airways invasive devices.METHODStudy with qualitative and quantitative approach, descriptive and exploratory type, whose investigative scenarios were adult inpatient units of a hospital in the West Frontier of Rio Grande do Sul. The study subjects consisted of nurses, nursing technicians and nursing assistants.RESULTSA total of 118 professionals were interviewed. We highlight the observed specific care with endotracheal tube and tracheostomy, management and assessment of the cuff and the criteria used to secretion aspiration.CONCLUSIONThere is a superficial nursing work in the patient direct care and a differentiation in relation to the perception of nurse technicians, especially those working in the intensive care unit, who presented major property and view of the patient's clinical status.

A new alternative method for testing skin irritation using a human skin model: a pilot study.

Studies assessing skin irritation to chemicals have traditionally used laboratory animals; however, such methods are questionable regarding their relevance for humans. New in vitro methods have been validated, such as the reconstructed human epidermis (RHE) model (Episkin®, Epiderm®). The comparison (accuracy) with in vivo results such as the 4-h human patch test (HPT) is 76% at best (Epiderm®). There is a need to develop an in vitro method that better simulates the anatomo-pathological changes encountered in vivo. To develop an in vitro method to determine skin irritation using human viable skin through histopathology, and compare the results of 4 tested substances to the main in vitro methods and in vivo animal method (Draize test). Human skin removed during surgery was dermatomed and mounted on an in vitro flow-through diffusion cell system. Ten chemicals with known non-irritant (heptylbutyrate, hexylsalicylate, butylmethacrylate, isoproturon, bentazon, DEHP and methylisothiazolinone (MI)) and irritant properties (folpet, 1-bromohexane and methylchloroisothiazolinone (MCI/MI)), a negative control (sodiumchloride) and a positive control (sodiumlaurylsulphate) were applied. The skin was exposed at least for 4h. Histopathology was performed to investigate irritation signs (spongiosis, necrosis, vacuolization). We obtained 100% accuracy with the HPT model; 75% with the RHE models and 50% with the Draize test for 4 tested substances. The coefficients of variation (CV) between our three test batches were <0.1, showing good reproducibility. Furthermore, we reported objectively histopathological irritation signs (irritation scale): strong (folpet), significant (1-bromohexane), slight (MCI/MI at 750/250ppm) and none (isoproturon, bentazon, DEHP and MI). This new in vitro test method presented effective results for the tested chemicals. It should be further validated using a greater number of substances; and tested in different laboratories in order to suitably evaluate reproducibility.

Transformed and nontransformed human T lymphocytes migrate to skin in a chimeric human skin/SCID mouse model.

To study human T cell migration to human skin in vivo, we grafted severe combined immunodeficient mice with 500-microm thick human skin. Two weeks after grafting, epidermal and dermal structures in the grafts were of human origin. When we intraperitoneally injected grafted mice with clones of the human HUT-78 T cell line derived from a patient with cutaneous T cell lymphoma and Sézary syndrome, we detected in the grafts the rare Vbeta23-Jbeta1.2 T cell receptor transcripts characteristic for the HUT-78 clones. These signals were found 2-6 d after cell injection in about 40% of the grafted and HUT-78 cell injected mice but not in grafts from mice that received no exogenous T cells. In contrast to HUT-78 cells, which only accumulate in low number, grafts topically challenged with nickel sufate in vaseline from mice that were injected with autologous nickel-reactive T cell lines led to massive accumulation of T cells within 3 d. Only scattered T cells accumulated in the skin when grafted mice received vaseline plus T cells, nickel sulfate alone, T cells alone, or nickel sulfate plus an allogeneic nickel-nonreactive T cell clone. When the T cell lines were labeled with the fluorochrome PKH-26 before cell injection, spots of fluorescent label in the size and shape of cells were found in the grafts challenged with nickel. Together, these results clearly demonstrate that human T cells can migrate to human skin in this chimeric human/mouse model.

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.

Neutron skin thickness in the droplet model with surface width dependence: Indications of softness of the nuclear symmetry energy

We analyze the neutron skin thickness in finite nuclei with the droplet model and effective nuclear interactions. The ratio of the bulk symmetry energy J to the so-called surface stiffness coefficient Q has in the droplet model a prominent role in driving the size of neutron skins. We present a correlation between the density derivative of the nuclear symmetry energy at saturation and the J/Q ratio. We emphasize the role of the surface widths of the neutron and proton density profiles in the calculation of the neutron skin thickness when one uses realistic mean-field effective interactions. Next, taking as experimental baseline the neutron skin sizes measured in 26 antiprotonic atoms along the mass table, we explore constraints arising from neutron skins on the value of the J/Q ratio. The results favor a relatively soft symmetry energy at subsaturation densities. Our predictions are compared with the recent constraints derived from other experimental observables. Though the various extractions predict different ranges of values, one finds a narrow window L∼45-75 MeV for the coefficient L that characterizes the density derivative of the symmetry energy that is compatible with all the different empirical indications.

A new alternative method for testing skin irritation using a fresh human skin model

La dermatite irritative est décrite comme une réaction réversible, non immunologique caractérisée par des lésions d'aspect très variable, allant de la simple rougeur jusqu'à la formation de bulles voire d'une nécrose, accompagnée de prurit ou d'une sensation de brûlure suite à I' application d'une substance chimique. Le teste de prédiction d'irritation cutanée est traditionnellement depuis les années 1940 le Test de Draize. Ce test consiste en l'application d'une substance chimique sur une peau rasée de lapin pendant 4h et de regarder à 24h si des signes cliniques d'irritations sont présents. Cette méthode critiquable autant d'un point de vue éthique que qualitative reste actuellement le teste le plus utilisé. Depuis le début des années 2000 de nouvelles méthodes in vitro se sont développées tel que le model d'épiderme humain recombiné (RHE). Il s agit d'une multicouche de kératinocyte bien différencié obtenu depuis une culture de don d'ovocyte. Cependant cette méthode en plus d'être très couteuse n'obtient au mieux que 76% de résultat similaire comparé au test in vivo humain. Il existe donc la nécessité de développer une nouvelle méthode in vitro qui simulerait encore mieux la réalité anatomique et physiologique retrouvée in vivo. Notre objectif a été de développer cette nouvelle méthode in vitro. Pour cela nous avons travaillé avec de la peau humaine directement prélevée après une abdominoplastie. Celle ci après préparation avec un dermatome, un couteau dont la lame est réglable pour découper l'épaisseur souhaitée de peau, est montée dans un système de diffusion cellulaire. La couche cornée est alors exposée de manière optimale à 1 ml de la substance chimique testée pendant 4h. L'échantillon de peau est alors fixé dans du formaldéhyde pour permettre la préparation de lames standards d'hématoxyline et éosine. L'irritation est alors investiguée selon des critères histopathologiques de spongioses, de nécroses et de vacuolisations cellulaires. Les résultats de ce.tte première batterie de testes sont plus que prometteurs. En effet, comparé au résultat in vivo, nous obtenons 100% de concordance pour les 4 même substances testes irritantes ou non irritantes, ce qui est supérieur au model d épiderme humain recombiné (76%). De plus le coefficient de variation entre les 3 différentes séries est inférieur à 0.1 ce qui montre une bonne reproductibilité dans un même laboratoire. Dans le futur cette méthode va devoir être testée avec un plus grand nombre de substances chimiques et sa reproductibilité évaluée dans différents laboratoires. Mais cette première evaluation, très encourageante, ouvre des pistes précieuses pour l'avenir des tests irritatifs.

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment

Purpose The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA) in rabbit eyes over a short-term period. Methods Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain) were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. Results Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ) Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. Conclusions Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

Liposomes and skin: From drug delivery to model membranes

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed "Transfersomes" by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. 'IYaditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes, Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to "fluidization" of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics. (c) 2008 Elsevier B.V. All rights reserved.

Development of an ex vivo human skin model for intradermal vaccination : tissue viability and Langerhans cell behaviour

The presence of resident Langerhans cells (LCs) in the epidermis makes the skin an attractive target for DNA vaccination. However, reliable animal models for cutaneous vaccination studies are limited. We demonstrate an ex vivo human skin model for cutaneous DNA vaccination which can potentially bridge the gap between pre-clinical in vivo animal models and clinical studies. Cutaneous transgene expression was utilised to demonstrate epidermal tissue viability in culture. LC response to the culture environment was monitored by immunohistochemistry. Full-thickness and split-thickness skin remained genetically viable in culture for at least 72 h in both phosphate-buffered saline (PBS) and full organ culture medium (OCM). The epidermis of explants cultured in OCM remained morphologically intact throughout the culture duration. LCs in full-thickness skin exhibited a delayed response (reduction in cell number and increase in cell size) to the culture conditions compared with split-thickness skin, whose response was immediate. In conclusion, excised human skin can be cultured for a minimum of 72 h for analysis of gene expression and immune cell activation. However, the use of split-thickness skin for vaccine formulation studies may not be appropriate because of the nature of the activation. Full-thickness skin explants are a more suitable model to assess cutaneous vaccination ex vivo.

Are clinical documents optimised for patient safety? A critical analysis of patient safety outcomes using the EDA error model

Iatrogenic errors and patient safety in clinical processes are an increasing concern. The quality of process information in hardcopy or electronic form can heavily influence clinical behaviour and decision making errors. Little work has been undertaken to assess the safety impact of clinical process planning documents guiding the clinical actions and decisions. This paper investigates the clinical process documents used in elective surgery and their impact on latent and active clinical errors. Eight clinicians from a large health trust underwent extensive semi- structured interviews to understand their use of clinical documents, and their perceived impact on errors and patient safety. Samples of the key types of document used were analysed. Theories of latent organisational and active errors from the literature were combined with the EDA semiotics model of behaviour and decision making to propose the EDA Error Model. This model enabled us to identify perceptual, evaluation, knowledge and action error types and approaches to reducing their causes. The EDA error model was then used to analyse sample documents and identify error sources and controls. Types of knowledge artefact structures used in the documents were identified and assessed in terms of safety impact. This approach was combined with analysis of the questionnaire findings using existing error knowledge from the literature. The results identified a number of document and knowledge artefact issues that give rise to latent and active errors and also issues concerning medical culture and teamwork together with recommendations for further work.

Effects of Micelles and Vesicles on the Oximolysis of p-Nitrophenyl Diphenyl Phosphate: A Model System for Surfactant-Based Skin-defensive Formulations against Organophosphates

The rates of oximolysis of p-nitrophenyl diphenyl phosphate (PNPDPP) by Acetophenoxime; 10-phenyl-10-hydi-oxyiminodecanoic acid; 4-(9-carboxynonanyl)-1-(9-carboxy-1-hydroyiminononanyl) benzene; 1-dodecyl-2-[(hydroxyimino)methyl]-pyridinium chloride (IV) and N-methylpyridinium-2-aldoxime chloride were determined in micelles of N-hexadecyl-N,N,N-trimethylammonium chloride (CTAC), N-hexadecyl-N,N-dimethylammonium propanesulfonate and dioctadecyldimethylammonium chloride (DODAC) vesicles. The effects of CTAC micelles and DODAC vesicles on the rates of oxymolysis of O,O-Diethyl O-(4-nitrophenyl) phosphate (paraoxon) by oxime IV were also determined. Analysis of micellar and vesicular effects on oximolysis of PNPDPP, using pseudophase or pseudophase with explicit consideration of ion exchange models, required the determination of the aggregate`s effects on the pK(a), of oximes and on the rates of PNPDPP hydrolysis. All aggregates increased the rate of oximolysis of PNPDPP and the results were analyzed quantitatively. In particular, DODAC vesicles catalyzed the reaction and increased the rate of oximolysis of PNPDPP by IV several million fold at pH`s compatible with pharmaceutical formulations. The rate increase produced by DODAC vesicles on the rate of oximolysis paraoxon by IV demonstrates the pharmaceutical potential of this system, since the substrate is used as an agricultural defensive agent and the surfactant is extensively employed in cosmetic formulations. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1040-1052, 2009