How many growing vestibular schwannomas tend to stop growing without any treatment?

OBJECTIVE: To determine the long-term, spontaneous growth arrest rates in a large cohort of vestibular schwannoma patients. METHODS: This paper describes a retrospective case series of 735 vestibular schwannoma patients organised into four groups: group A patients showed tumour growth which then stopped without any treatment; group B patients showed tumour growth which continued, but were managed conservatively; group C patients had a growing vestibular schwannoma and received active treatment; and group D patients had a stable, non-growing vestibular schwannoma. Demographics, tumour size and vestibular schwannoma growth rate (mm/month) were recorded. RESULTS: A total of 288 patients (39.2 per cent) had growing vestibular schwannomas. Of the patients, 103 (35.8 per cent) were managed conservatively, with 52 patients (50.5 per cent of the conservative management group, 18 per cent of the total growing vestibular schwannoma group) showing growth arrest, which occurred on average at four years following the diagnosis. Eighty-two per cent of vestibular schwannomas stopped growing within five years. Only differences between age (p = 0.016) and vestibular schwannoma size (p = 0.0008) were significant. CONCLUSION: Approximately 20 per cent of growing vestibular schwannomas spontaneously stop growing, predominantly within the first five years; this is important for long-term management.

Review of critical factors affecting analytical characteristics of serological and molecular assays.

Analytical characteristics of diagnostic tests, encompassing estimates of repeatability, analytical specificity (ASp) and analytical sensitivity (ASe), are determined during Stage 1 of the OIE Assay Validation Pathway. Repeatability (an estimate of assay precision and robustness), ASp (measuring only what an assay is intended to measure) and ASe (synonymous with the lower limit of detection) are fundamental parameters that determine future test performance. Importantly, these parameters provide the basis for deciding whether a prototype assay progresses to the next stage of the OIE Assay Validation Pathway (determination of diagnostic characteristics) or is withdrawn in favour of alternate tests with better analytical performance characteristics. Implicit in the successful development and validation of any assay is a sound understanding of the target pathogen, the disease pathogenesis in susceptible hosts, the fundamental technical principles that underliey each test system, and its intended use. Factors that affect analytical characteristics of diagnostic assays are numerous and may vary according to each assay type. Using, as examples, development of an enzyme-linked immunosorbent assay for detection of antibodies to capripoxviruses, and the comparative assessment of three quantitative real-time polymerase chain reactions for detection of African swine fever virus DNA, the main factors affecting analytical characteristics of serological and molecular assays are considered. As reviewed within, comprehensive and well-designed experiments are required to develop and optimise assays with favourable analytical characteristics. The underlying principles are broadly applicable to all assay types and, when conducted with appropriate rigour, provide the foundations for high-quality diagnostic tests that are fit for their intended purpose(s).

Les caractéristiques de performance analytique des tests diagnostiques, qui recouvrent l'estimation de la répétabilité, de la spécificité analytique (SpA) et de la sensibilité analytique (SeA) d'un test sont déterminées lors de l'étape 1 du processus de l'OIE relatif à la validation des essais. La répétabilité (une estimation de la précision et de la robustesse de l'essai), la SpA (qui mesure uniquement ce que l'essai est destiné à mesurer) et la SeA (synonyme de limite inférieure de détection) sont des paramètres essentiels qui déterminent les futures performances du test. Il est important de noter que ces paramètres apportent les éléments essentiels pour décider si l'essai peut passer à l'étape suivante du processus de validation de l'OIE (détermination des caractéristiques diagnostiques) ou s'il doit céder la place à des tests alternatifs dotés de meilleures caractéristiques de performance analytique. Pour réussir la mise au point et la validation d'un essai, certaines conditions préalables doivent être réunies : bien connaître l'agent pathogène cible et la pathogenèse de la maladie chez les réservoirs sensibles, ainsi que les grands principes techniques sous-jacents à chaque système de test et l'emploi prévu du test. Les facteurs affectant les caractéristiques analytiques d'un essai diagnostique sont nombreux et varient suivant le type d'essai dont il s'agit. À partir d'exemples portant sur une épreuve immuno-enzymatique mise au point pour la détection des anticorps dirigés contre les capripoxvirus et sur l'évaluation comparative de trois techniques d'amplification en chaîne par polymérase quantitative en temps réel pour la détection de l'ADN viral de la peste porcine africaine, les auteurs mettent en exergue les principaux facteurs qui peuvent altérer les caractéristiques analytiques des essais sérologiques et moléculaires. Il ressort de cette évaluation que des expérimentations complètes et bien conçues sont nécessaires pour mettre au point et optimiser des essais possédant les caractéristiques analytiques souhaitées. En général, les principes sous-jacents sont applicables à tous les types d'essai, et s'ils sont appliqués de manière rigoureuse, ils fournissent la garantie de disposer de tests diagnostiques de qualité élevée et aptes à l'emploi ou aux emplois prévus.

La primera etapa del proceso de validación de ensayos de la OIE es aquella en que se determinan las características analíticas de una prueba de diagnóstico, o dicho de otro modo, en que se calculan los valores de repetibilidad (estimación de la precisión y robustez del ensayo), especificidad analítica (es decir, el hecho de que el ensayo mida únicamente lo que está destinado a medir) y sensibilidad analítica (sinónimo referido al límite inferior de detección), que son tres parámetros fundamentales para determinar el futuro rendimiento de una prueba. Un aspecto importante es que estos parámetros sientan las bases a partir de las cuales decidir si un prototipo de ensayo debe pasar a la siguiente etapa del proceso de validación de ensayos de la OIE (determinación de las características de diagnóstico) o si vale más retirarlo en beneficio de otras pruebas que presenten mejores características de rendimiento analítico. Un factor implícito en el éxito de todo proceso de desarrollo y validación de ensayos es un sólido conocimiento del patógeno en cuestión, la patogénesis de la enfermedad en los anfitriones sensibles, los principios técnicos fundamentales en que reposa cada sistema de ensayo y sus usos previstos. Los numerosos factores que influyen en las características analíticas de un ensayo de diagnóstico difieren en función del tipo de ensayo. Utilizando como ejemplo el desarrollo de un ensayo inmunoenzimático de detección de anticuerpos contra capripoxvirus y la evaluación comparativa de tres PCR cuantitativas en tiempo real para detectar ADN del virus de la peste porcina africana, los autores pasan revista a los principales factores que determinan las características analíticas de los ensayos serológicos y moleculares. Como explican, para desarrollar y optimizar ensayos que presenten características analíticas favorables se requieren experimentos completos y bien concebidos. Los principios subyacentes son válidos en general para todo tipo de ensayos y, cuando se aplican con el debido rigor, sientan las bases para obtener pruebas de diagnóstico de gran calidad y adaptadas a la(s) finalidad(es) prevista(s).

Introduction - Validation of tests for OIE-listed diseases as fit-for-purpose in a world of evolving diagnostic technologies.

The World Organisation for Animal Health (OIE) has made leading contributions to the discipline of test validation science by providing standards and guidelines that inform the test validation process in terrestrial and aquatic animals. The OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals, and the Manual of Diagnostic Tests for Aquatic Animals describe the test validation pathway in the context of fitness for purpose, elaborate on the importance of diagnostic sensitivity (DSe) and specificity (DSp) as measures of test accuracy, and designate additional factors (e.g. test cost, laboratory throughput capacity and rapidity of test results) that influence choices of a single test over others or the inclusion of a new test in a diagnostic process that includes multiple tests. This paper provides examples of each of the six main testing purposes listed in the Terrestrial Manual and describes additional metrics such as ruggedness and robustness that should be included in the validation of point-of-care tests. Challenges associated with new diagnostic technologies and platforms are described. Validated tests with estimates of DSe and DSp are needed to measure confidence in test results for OIE-listed diseases, to facilitate risk assessments related to animal movement, to estimate true prevalence, and for certification of disease freedom and use in epidemiological (risk factor) studies.

L'Organisation mondiale de la santé animale (OIE) a apporté d'importantes contributions dans le domaine de la validation des tests en élaborant des normes et des lignes directrices qui informent sur le processus de validation des tests chez les animaux terrestres et aquatiques. Le Manuel des tests de diagnostic et des vaccins pour les animaux terrestres et le Manuel des tests de diagnostic pour les animaux aquatiques de l'OIE décrivent le processus de validation des tests dans le contexte de leur aptitude à l'emploi, expliquent l'importance de la sensibilité (DSe) et de la spécificité (DSp) diagnostiques pour mesurer l'exactitude des tests, et désignent d'autres facteurs (ex. coût des tests, capacité de traitement des laboratoires et rapidité d'obtention des résultats des tests) qui influencent le choix d'un test par rapport à un autre ou l'inclusion d'un nouveau test dans un processus de diagnostic composé de multiples tests. Le présent article fournit des exemples pour chacun des six principaux objectifs définis pour les tests figurant dans le Manuel terrestre et décrit des mesures supplémentaires, telle la robustesse (aussi bien interne qu'externe), qu'il conviendrait d'inclure dans la validation des tests au point d'intervention. Il aborde également les défis soulevés par les nouvelles technologies et plateformes de diagnostic. Des tests validés accompagnés d'estimations de la DSe et de la DSp sont nécessaires pour mesurer la fiabilité des résultats des tests pour les maladies listées par l'OIE, faciliter les évaluations des risques associés aux mouvements des animaux, estimer le véritable taux de prévalence et certifier l'absence de maladies ; ils sont également indispensables pour les études (des facteurs de risque) épidémiologiques.

La Organización Mundial de Sanidad Animal (OIE), con su labor de elaboración de normas y directrices que fundamentan el proceso de validación de pruebas para enfermedades de los animales terrestres y acuáticos, ha hecho aportaciones punteras a la disciplina científica que se ocupa de la validación de pruebas. En su Manual de las Pruebas de Diagnóstico y de las Vacunas para los Animales Terrestres y su Manual de las Pruebas de Diagnóstico para los Animales Acuáticos, la OIE describe el procedimiento de validación de pruebas en clave de idoneidad para determinados propósitos, ahonda en la importancia de la sensibilidad y la especificidad diagnósticas (DSe y DSp) como medidas de la exactitud de una prueba y señala otros factores (como el costo de la prueba, la productividad del laboratorio o la rapidez de los resultados) que también influyen en la elección de una determinada prueba por delante de otras o en la inclusión de una nueva prueba en un proceso de diagnóstico que entraña el uso de varias. Los autores ofrecen ejemplos de cada uno de los seis principales propósitos con las que puede utilizarse una prueba, según vienen enunciados en el Manual Terrestre, y describen otros parámetros que es preciso tener en cuenta a la hora de validar pruebas practicadas en el punto de consulta, como la robustez o también la solidez (ruggedness en inglés; llamada a veces «robustez interlaboratorios¼). También describen las dificultades ligadas a nuevas tecnologías y plataformas de diagnóstico. Se necesitan pruebas validadas y acompañadas de un cálculo de la DSe y la DSp para fines tan diversos e importantes como medir la confianza que merecen los resultados de pruebas para enfermedades inscritas en las listas de la OIE, facilitar la evaluación del riesgo ligado al desplazamiento de animales, estimar la prevalencia real, certificar la ausencia de enfermedad o realizar estudios epidemiológicos (factores de riesgo).

Multi parametric biophysical assessment of treatment effects on xerotic skin.

Background: Topical moisturizing products are widely used to alleviate the problems associated with xerotic skin. Their use affects many properties of the stratum corneum (SC) in a complex and interrelated manner. The range of measurement techniques available to the researcher has increased in recent years. However, few studies have looked for correlations between the different techniques for assessing how aspects of xerotic skin change over time as a result of topical moisturizer usage. Objectives: A 3-week in vivo study using an oil-in-water based moisturizing product and an untreated site was conducted to determine the clinical significance of and any correlations between a range of different approaches for the measurement of skin lipid content and also skin hydration and visual grading of dry skin. Methods: A range of traditional and more recently developed skin measurement techniques have been used to examine a variety of SC properties in normal and xerotic skin during topical moisturizer usage. Results: In vivo confocal Raman spectroscopy and analysis of SC lipids from tape strips both showed an increase in SC lipid level and organization after 3 weeks of moisturizer usage on xerotic skin. Hydration, measured both optically and electrically, also increased and skin barrier function improved, with strong correlations between the different measures of dryness being observed. Conclusions: Strong correlations were observed between the skin measurements for lipid assessment and skin hydration with regard to the assessment of xerotic skin, providing valuable new information for future in vivo clinical research into dry and atopic skin. Keywords biophysical assessment, skin barrier, skin hydration, topical moisturizers, Xerosis.

UV reflectance photography of skin: what are you imaging?

OBJECTIVE: Photography can be a powerful tool for researching the skin. Moving outside the visible spectrum and into the ultra violet (UV) presents a unique set of challenges to the skin photographer because of the restrictions imposed by the equipment being used. This article discusses these challenges in relation to camera sensitivity, lens and filter transmission and lighting spectrum, with the aim of demystifying what is actually being captured when imaging skin. METHODS: In addition to a discussion of existing data on the subject of camera sensor sensitivity, filter transmission and flash spectral analysis, transmission in the UV of a variety of camera lenses using a new method has been carried out. RESULTS: Using the described approach, lens transmission between 280 and 420 nm of a range of lenses has been measured. Combining this with camera sensor sensitivity data and filter and light source characteristics, it has been possible to determine an overall, harmonized, spectral sensitivity curve for what is being imaged with a given setup. CONCLUSIONS: UV reflectance photography, while a powerful tool, is often misunderstood and misreported as to what is actually being imaged. By combining measurements on camera sensitivity, lens and filter transmission and light source spectra the researcher can more fully understand what is they are actually measuring, thereby enabling better communication with the consumer on what they are seeing and a more complete description for any claims support.

OBJECTIF: La photographie peut constituer un outil puissant pour effectuer des recherches sur la peau. Toutefois, qui veut dépasser le spectre visible et photographier l'ultraviolet (UV) doit faire face à un ensemble unique de défis dus aux limites imposées par l'équipement utilisé. Cet article présente ces défis, en lien avec la sensibilité de l'appareil photo, la/les lentille(s), le filtre de transmission et le spectre lumineux afin de mieux comprendre ce qui est enregistré par l'appareil lorsque l'on prend une photo de la peau. MÉTHODES: Après un examen des données existantes sur la sensibilité des capteurs d'appareil photo, les filtres de transmission et les analyses spectrales flash, une nouvelle méthode est essayée afin d'éprouver la transmission des UV via diverses lentilles photo. RÉSULTATS: À l'aide de l'approche décrite, des transmissions d'entre 280 et 420 nm ont été mesurées pour plusieurs lentilles. En combinant ces mesures avec les données de sensibilité du capteur de l'appareil photo ainsi que les caractéristiques des filtres et de la source lumineuse, on a pu déterminer une courbe harmonisée de la sensibilité spectrale pour ce qui est photographié dans des circonstances données. CONCLUSIONS: Si la photographie UV par réflectance constitue un outil puissant, elle demeure souvent mal connue, et on comprend mal ce qui est réellement pris en photo. En combinant les mesures de la sensibilité de l'appareil photo, de lentilles, de filtres de transmission et de spectres lumineux des sources, le chercheur peut mieux comprendre ce qu'il mesure réellement, ce qui permet une meilleure communication avec le client quant au(x) résultat(s) des photographies et une description plus exhaustive en cas de réclamation.

Benefits of pre-labyrinthectomy intratympanic gentamicin: contralateral vestibular responses.

OBJECTIVE: To determine the impact of pre-operative intratympanic gentamicin injection on the recovery of patients undergoing translabyrinthine resection of vestibular schwannomas. METHODS: This prospective, case-control pilot study included eight patients undergoing surgical labyrinthectomy, divided into two groups: four patients who received pre-operative intratympanic gentamicin and four patients who did not. The post-operative six-canal video head impulse test responses and length of in-patient stay were assessed. RESULTS: The average length of stay was shorter for patients who received intratympanic gentamicin (6.75 days; range, 6-7 days) than for those who did not (9.5 days; range, 8-11 days) (p = 0.0073). Additionally, the gentamicin group had normal post-operative video head impulse test responses in the contralateral ear, while the non-gentamicin group did not. CONCLUSION: Pre-operative intratympanic gentamicin improves the recovery following vestibular schwannoma resection, eliminating, as per the video head impulse test, the impact of labyrinthectomy on the contralateral labyrinth.

Cochlear patency following translabyrinthine vestibular schwannoma resection: implications for hearing rehabilitation.

OBJECTIVE: To examine when cochlear fibrosis occurs following a translabyrinthine approach for vestibular schwannoma resection, and to determine the safest time window for potential cochlear implantation in cases with a preserved cochlear nerve. METHODS: This study retrospectively reviewed the post-operative magnetic resonance imaging scans of patients undergoing a translabyrinthine approach for vestibular schwannoma resection, assessing the fluid signal within the cochlea. Cochleae were graded based on the Isaacson et al. system (from grade 0 - no obstruction, to grade 4 - complete obliteration). RESULTS: Thirty-nine patients fulfilled the inclusion criteria. The cochleae showed no evidence of obliteration in: 75 per cent of patients at six months, 38.5 per cent at one year and 27 per cent beyond one year. Most changes happened between 6 and 12 months after vestibular schwannoma resection, with cases of an unobstructed cochlear decreasing dramatically, from 75 per cent to 38.5 per cent, within this time. CONCLUSION: The progress of cochlear obliteration that occurred between 6 and 12 months following vestibular schwannoma resection indicates that the first 6 months provides a safer time window for cochlear patency.

3D-printed Franz type diffusion cells.

OBJECTIVE: Franz cells are routinely used to measure in vitro skin permeation of actives and must be inert to the permeant under study. The aim of the present work was to develop and manufacture transparent Franz-type diffusion cells using 3D printing. Printouts were then tested using a range of model active compounds. The study also aims to identify the critical 3D-printing parameters necessary for the process, including object design, choice of printing resin, printout curing and post-curing settings and introduction of model coatings. METHODS: Transparent Franz cells were constructed using an online computer aided design program and reproduced with different stereolithography 3D printers. The two acrylate-based resins used for the fabrication process were a commercially available product and a polymer synthesised in-house. Comparative studies between glass and 3D-printed Franz cells were conducted with selected model actives: terbinafine hydrochloride (TBF), niacinamide (NIA), diclofenac free acid (DFA) and n-methyl paraben (MPB). In preliminary studies, MPB showed the lowest recovery when exposed to the receptor compartment of 3D printed cells. Consequently, in vitro permeation studies were carried out using only MPB with polydimethylsiloxane (PDMS) membrane. RESULTS: A decrease in the amounts of selected compounds was observed for transparent 3D-printed Franz cells compared to glass cells. MPB showed the lowest recovery (53.8 ± 13.1%) when compared with NIA (74.9 ± 4.0%), TBF (81.5 ± 12.0%) and DFA (90.2 ± 12.9%) after 72 h. Permeation studies conducted using 3D-printed transparent cells with PDMS membrane also showed a decrease in MPB recovery of 51.4 ± 3.7% for the commercial resin and 94.4 ± 3.5% for the polymer synthesised in-house, when compared to glass cells. Although hydrophobic coatings were subsequently applied to the 3D-printed cells, the same reduction in MPB concentration was observed in the receptor solution. CONCLUSION: Transparent Franz cells were successfully prepared using 3D printing and were observed to be robust and leak-proof. There are few resins currently available for preparation of transparent materials and incompatibilities between the actives investigated and the 3D-printed cells were evident. Hydrophobic coatings applied as barriers to the printed materials did not prevent these interactions.

Calibrating UVA reflectance photographs - standardisation using a low-cost method.

OBJECTIVE: While established methods for the calibration of visible light photographs are well defined, the use of these approaches in UVA reflectance photography is less well understood. A systematic, low-cost and simple method for the production of well-defined grey calibration standard targets for UVA reflectance photography, with a particular emphasis on low reflectivity surfaces, along with a comparison with standard visible light photographic standards is presented here. METHODS: Grey calibration standard targets suitable for use in the UVA region were produced, based on optimised methods from the literature. The standards were assessed using UV-Visible reflection spectroscopy, and visible and UVA light photography, and their behaviour compared with a commercially available visible light photographic calibration chart. RESULTS: Calibration standards with a relatively flat reflection response in the UVA region with a variety of reflectances between 2% and 35% were prepared. Imaging of the standards in both UV and visible light demonstrated the differences between these standards and the ones specifically designed for visible light photography. CONCLUSIONS: A low cost and simple method for the production of low reflectance UVA calibration targets, suitable for UVA reflectance photography has been described and tested against commercially available visual light calibration standards. These new UV suitable standards have potential for use in a wide range of applications such as forensics, biology and cosmetic science.

Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo.

Protein Phosphatase 2A (PP2A) enzymes counteract diverse kinase-driven oncogenic pathways and their function is frequently impaired in cancer. PP2A inhibition is indispensable for full transformation of human cells, but whether loss of PP2A is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe spontaneous tumor development in knockout mice for Ppp2r5d, encoding the PP2A regulatory B56δ subunit. Several primary tumors were observed, most commonly, hematologic malignancies and hepatocellular carcinomas (HCCs). Targeted immunoblot and immunohistochemistry analysis of the HCCs revealed heterogeneous activation of diverse oncogenic pathways known to be suppressed by PP2A-B56. RNA sequencing analysis unveiled, however, a common role for oncogenic c-Myc activation in the HCCs, independently underscored by c-Myc Ser62 hyperphosphorylation. Upstream of c-Myc, GSK-3ß Ser9 hyperphosphorylation occurred both in the HCCs and non-cancerous B56δ-null livers. Thus, uncontrolled c-Myc activity due to B56δ-driven GSK-3ß inactivation is the likely tumor predisposing factor. Our data provide the first compelling mouse genetics evidence sustaining the tumor suppressive activity of a single PP2A holoenzyme, constituting the final missing incentive for full clinical development of PP2A as cancer biomarker and therapy target.

Understanding sunscreen SPF performance using cross-polarized UVA reflectance photography.

OBJECTIVES: Objective methods for understanding sunscreen behaviour in vitro before they are applied to the skin have failed to keep pace with the ever-increasing demands for higher SPF scores where the products are absorbing more and more similar levels of UV. A novel method for visualizing the spreading and location of SPF ingredients based on cross-polarized UVA reflectance photography is described here which gives new insights into the formation of final film morphology and how it correlates with in vivo SPF efficacy for a set of test products. METHODS: High-resolution UVA-based images of sunscreen films spread onto PMMA plates were captured using a modified commercial SLR camera in a custom imaging system. Visual grading and image analysis were used to describe the overall UVA absorbance and streakiness of the resultant films, and the data compared with both in vivo and calculated in vitro SPF scores for the products. RESULTS: Differences were observed between the products in terms of how they spread during application. A strong correlation was observed between the evenness of the resultant film as determined from the photographs and final in vivo SPF scores. CONCLUSIONS: Cross-polarized UVA reflectance photography has been demonstrated to be a valuable new method for assessing sunscreen distribution after spreading and to differentiate product based on film morphology, as well as strongly correlating with final in vivo behaviour.

Understanding the effects of topography on skin moisturization measurement via two-dimensional capacitance imaging.

OBJECTIVE: Methods which assess skin moisturization based on changes in its electrical properties are widely used in both cosmetic and medical research industries. However, the devices themselves often give results which are significantly different to each other. Recently two-dimensional imaging moisturization systems have become commercially available, which have the capability to provide a more detailed assessment of what is contributing to measured skin moisturization. Presented here is a new in vitro method for preparing textured model test substrates for use with these devices, and results of their use to provide a clearer insight into the devices operation. METHODS: A variety of different textured model test substrates were measured using a commercially available skin moisturization measurement device, the Epsilon. The response of the Epsilon was also tested against conventional skin moisturization devices. RESULTS: Surface morphology of model test substrates was found to have a significant influence on the measurement of its electrical properties with both the conventional and two-dimensional skin moisturization measurement devices. Through modification of the areas of the image being assessed for the two-dimensional moisturization mapping device, the parts of the model test substrate in contact with the device were indentified and analysed separately to areas not in contact with the sensor. This provided a more robust assessment of the electrical properties of substrate itself, rather than being influenced by texture like the conventional skin moisturization measurement devices. CONCLUSIONS: While the two-dimensional moisturization mapping systems can be used like a conventional electrical skin measurement device giving a simple overall reading of skin moisturization for the test area, their true value over existing electrical measures comes from its ability to isolate the skin itself from areas which are not in contact with the sensor.

Chemical ultraviolet absorbers topically applied in a skin barrier mimetic formulation remain in the outer stratum corneum of porcine skin.

The objective of the present study was to evaluate the fate of three chemical sunscreens, isoamyl p-methoxycinnamate (IPMC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and bis-ethylhexylphenol methoxyphenyl triazine (BEMT), topically applied to mammalian skin from a skin barrier mimetic oil-in-water formulation. High Performance Liquid Chromatography (HPLC) methods were developed for the analysis of each molecule and validated. Franz cell permeation studies were conducted following application of finite doses of the formulations to excised porcine skin. A vehicle formulation containing no sunscreens was evaluated as a control. Permeation studies were conducted for 12h after which full mass balance studies were carried out. Analysis of individual UV sunscreens was achieved with HPLC following application of the formulation to the skin with no interference from the vehicle components. No skin permeation of any of the chemical sunscreens was evident after 12h. While sunscreens were detected in up to 12 tape strips taken from the SC, 87% or more of the applied doses recovered in the first 5 tape strips. When corrected for the amount of protein removed per tape strip this corresponded to a penetration depth in porcine stratum corneum of ∼1.7µm. Mass balance studies indicated total recovery values were within accepted guidelines for cosmetic formulations. Overall, only superficial penetration into the SC was observed for each compound. These findings are consistent with the physicochemical properties of the selected UV absorbing molecules and their formulation into an ordered biomimetic barrier formulation thus support their intended use in topical consumer formulations designed to protect from UV exposure. To our knowledge this is the first report of depth profiling of chemical sunscreens in the SC that combines tape stripping and protein determination following in vitro Franz cell studies.

Understanding effects of topical ingredients on electrical measurement of skin hydration.

OBJECTIVE: Methods that assess skin hydration based on changes in its electrical properties are widely used in both cosmetic and medical research. However, the devices themselves often give results which are significantly different to each other. Although some work has previously been carried out to try and understand what these devices are actually reading, it was based on a technique for measuring the devices' responses to filter discs impregnated with different liquids, which could in itself be influencing the measurements. Presented here is a new method for measuring the devices' direct responses to different materials and solutions which removes any other confounding effects, thereby providing a clearer insight into their operation. METHODS: The responses of a variety of different liquids and solutions were measured using the Corneometer® and Skicon® . A new method is presented, based on the use of a custom-designed PTFE block to hold the liquids, allowing their measurement without using a filter paper. This method was developed and tested against the existing filter paper-based approach. RESULTS: Differences were observed in results between filter paper- and PTFE block-based approach, indicating that the filter paper itself is capable of influencing the measurements and as such is not to be recommended for assessing how different liquids impact on results from the devices. A positive correlation was observed between Corneometer® and Skicon® readings for certain solutions and under certain conditions. A large influence of salt concentration was noted for the Skicon® device with no or minimal impact from the actual water itself, humectants and emollients. Salts, emollients, water and humectants were observed to have an effect on Corneometer® readings. CONCLUSIONS: Both the Corneometer® and Skicon® were influenced to different extents by chemicals other than water and therefore cannot be seen purely as measures of skin 'hydration'. Although there is strong evidence that the devices do correlate with expert assessment of skin dryness, the level of water in the skin is only part of the story when it comes to understanding the benefits of topical moisturizing products applied to the skin. An alternative approach would be to consider skin 'moisturization' as a property which is influenced by water, salts and other materials such as humectants and emollients, which is more consistent with how the stratum corneum itself helps to maintain its plasticity and flexibility. In the work presented here, the Corneometer® was more suited to providing a measurement which reflects the impact of multiple different components.

Method for quantification of oils and sebum levels on skin using the Sebumeter(®).

OBJECTIVE: The Sebumeter(®) is widely used in both cosmetic and medical research, for measuring changes in sebum levels on skin. It is commonly reported that the units correlated to a mass of sebum on the skin in µg cm(-2) ; however, validation for this has not been published. Also, its use for assessing the presence of other oily materials which are widely utilized in topical skincare products on skin has not been widely discussed. Determining a calibration scale and whether the response of the device is linear with the level of oils present enables quantification of the output of the device, and would validate the device for claims substantiation. METHODS: Different doses of a variety of oily materials (paraffin oil, white soft paraffin, capric-caprylic triglyceride, 350cSt silicone fluid and synthetic sebum) were applied to skin, and the Sebumeter(®) used to collect and quantify them. The mass per square centimetre of the oily material delivered to the skin was then compared to the Sebumeter(®) output to develop calibration curves for the different materials. Measurements were carried out on a single volunteer as this work was to verify the concept of quantitative oil assessment using the device. RESULTS: A linear correlation between the mass of the oily material and the Sebumeter(®) output was seen for all the materials tested. However, the absolute response of the device was different for each material, and the output values did not directly give the mass of material on the skin in µg cm(-2) . As part of the calibration, it was also demonstrated that to remove all the oily material from a given area of the skin required multiple 30-s applications of the Sebumeter(®) cartridge. CONCLUSIONS: The Sebumeter(®) is a precise analytical instrument capable of quantitative measurement of deposition of oily materials onto skin from topical products (down to the µg cm(-2) level), as well as its traditional use of measuring sebum levels. However, the output values do not directly correlate with the mass of oil present, and generation of a calibration curve is necessary for any ingredient of interest to produce quantitative data for claim support and formulation development.

Neurenteric cyst presenting with stridor and dysphagia: case report and literature review.

OBJECTIVE: Neurenteric cysts are rare lesions that account for 0.7-1.3% of all spinal cord tumours. We report the first ever case of a neurenteric cyst presenting with stridor and dysphagia. A literature review on the presentation and management of these lesions is also included. METHODS: A MEDLINE search of articles using the terms 'neurenteric cyst', 'intraspinal cyst', 'enterogenous cyst', 'intramedullary cyst' along with diagnosis, presentation and management was performed. Suitable references from these articles were also reviewed. RESULTS: All published evidence on neurenteric cysts are either case series or case reports (level IV/V) with the largest case series reporting 23 patients from a single institution. CONCLUSION: Neurenteric cysts are rare spinal cord lesions that usually present with focal neurological signs and managed within neurosurgical units. This is the first reported case of a neurenteric cyst presenting with upper aerodigestive tract symptoms warranting specialist ear, nose and throat input.

Within herd transmission and evaluation of the performance of clinical and serological diagnosis of foot-and-mouth disease in partially immune cattle herds.

The control of foot-and-mouth disease (FMD) in vaccinated populations relies upon surveillance activities such as clinical inspections (CI) and serological monitoring. New evidence to refine current surveillance guidelines has been provided by evaluating (1) the diagnostic performance of CI and serological tests for detection of FMD virus (FMDV) non-structural proteins (NSP), and (2) the within-herd transmission of the virus in partially immune cattle. Data came from 23 affected herds during an epidemic of FMDV type O in Bolivia, in 2007. All cattle (n=957) in these herds were clinically inspected and serum samples were collected one month after the last animal with clinical signs was detected. Samples were tested for the presence of antibodies against NSP using the PANAFTOSA 3ABC-ELISA test and a subset of samples were tested using the enzyme-linked immunoelectrotransfer blot assay (EITB). Data from clinical and serological diagnoses were analysed using a Bayesian model. The sensitivity Se and specificity Sp of the tests, as well as the prevalence and the within-herd reproduction ratio R of FMDV were estimated. In addition, risk factors for infection were identified. The Se of CI, the 3ABC-ELISA and the EITB tests were estimated to be 0.30, 0.88 and 0.96 respectively. The estimated Sp, in the same order, were 0.88, 0.93 and 0.97. The within-herd prevalence of infected animals ranged from 0.04 to 0.91 and R ranged from 1.02 to 2.68. It was observed that cattle coming from areas with high vaccination coverage had a lower risk of becoming infected than home-bred cattle from the affected herds, where vaccination coverage was thought to be low. Although these estimates come from herds kept under specific conditions, they provide a reference for future surveillance design and can inform simulation models for surveillance and control of FMD in similar cattle populations.

Development and validation of a 3ABC antibody ELISA in Australia for foot and mouth disease.

OBJECTIVE: To measure the diagnostic performance of an Australian-developed ELISA for the detection of antibodies against the non-structural proteins (NSP) 3ABC of the foot and mouth disease (FMD) virus. DESIGN: Test development and validation study. METHODS: The diagnostic specificity was determined using 2535 sera from naïve animals and 1112 sera from vaccinated animals. Diagnostic sensitivity was calculated from the data for 995 sera from experimentally and field-infected animals from FMD-endemic countries in South East Asia. A commercial ELISA detecting antibodies against FMD virus NSP was used as the reference test to establish relative sensitivity and specificity. Bayesian latent class analysis was performed to corroborate results. The diagnostic window and rate of detection were determined at different times using sera from cattle, sheep and pigs before and after infection, and after vaccination and subsequent infection. Repeatability and reproducibility data were established. RESULTS: At 35% test cut-off, the 3ABC ELISA had an overall diagnostic sensitivity of 91.5% and diagnostic specificity of 96.4%. The diagnostic sensitivity in vaccinated and subsequently infected cattle was 68.4% and diagnostic specificity in vaccinated cattle was 98.0%. CONCLUSIONS: The 3ABC ELISA identified field and experimentally infected animals, as well as vaccinated and subsequently infected animals. Diagnostic sensitivity and specificity estimates for other FMD NSP tests are comparable with the results obtained in this study. This NSP ELISA was found to be 'fit for purpose' as a screening assay at the herd level to detect viral infection and also to substantiate absence of infection.