CRTH2 expression on T cells in asthma

Mast cell-derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G-protein-coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1·8% ± 0·2) and normal (1·6% ± 0·2) subjects. CRTH2 was enriched significantly on interleukin (IL)-4+/IL-13+ T cells compared to interferon (IFN)-γ+ T cells (P < 0·001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2·3% ± 0·6) and normal subjects (0·3% ± 0·1), and there was a significant difference between the two groups (P < 0·05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood–BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL-4+ and IL-13+ T cells compared to IFN-γ+ T cells was also seen in BAL from asthmatics (P < 0·001). CRTH2 is expressed preferentially by IL-4+/IL-13+ T cells compared to IFN-γ+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung

Texture-based Classification for the Automatic Rating of the Perivascular Spaces in Brain MRI

Los espacios perivasculares (EVP) se relacionan con una cognición deficiente, depresión en la edad avanzada, enfermedad de Parkinson, inflamación, hipertensión y enfermedad de pequeños vasos cerebrales, cuando están agrandados y son visibles en imágenes de resonancia magnética (MRI). En este artículo exploramos cómo clasificar la densidad del PVS agrandado en los ganglios basales (BG) mediante la descripción de la textura de la RM cerebral estructural. La textura de la región BG se describe mediante estadísticas de primer orden y características derivadas de la matriz de co-ocurrencia, ambas computadas a partir de la imagen original y los coeficientes producidos por la transformada de wavelet discreta (WSF y WCF, respectivamente), y patrones binarios locales (LBP). Los resultados experimentales con un clasificador de Máquina de vectores de soporte (SVM) muestran que WCF logra una precisión del 80.03%

Fungal allergy in asthma-state of the art and research needs

Sensitization to fungi and long term or uncontrolled fungal infection are associated with poor control of asthma, the likelihood of more severe disease and complications such as bronchiectasis and chronic pulmonary aspergillosis. Modelling suggests that >6.5 million people have severe asthma with fungal sensitizations (SAFS), up to 50% of adult asthmatics attending secondary care have fungal sensitization, and an estimated 4.8 million adults have allergic bronchopulmonary aspergillosis (ABPA). There is much uncertainty about which fungi and fungal allergens are relevant to asthma, the natural history of sensitisation to fungi, if there is an exposure response relationship for fungal allergy, and the pathogenesis and frequency of exacerbations and complications. Genetic associations have been described but only weakly linked to phenotypes. The evidence base for most management strategies in ABPA, SAFS and related conditions is weak. Yet straightforward clinical practice guidelines for management are required. The role of environmental monitoring and optimal means of controlling disease to prevent disability and complications are not yet clear. In this paper we set out the key evidence supporting the role of fungal exposure, sensitisation and infection in asthmatics, what is understood about pathogenesis and natural history and identify the numerous areas for research studies

DISTRIBUTION, INHERITANCE, AND PROPERTIES OF AN ANTIGEN, MUB1, AND ITS RELATION TO HEMOLYTIC COMPLEMENT

An antigen, MuB1, present in the sera of some mice, can elicit a precipitating antibody in certain other strains of mice. An antibody to the antigen MuB1 can also be elicited in rabbits. 99 strains and substrains of inbred mice were tested for the presence of MuB1; the antigen was found in the sera of 44 strains (61 per cent) and 14 DBA substrains (52 per cent). Evidence is presented indicating that mice lacking MuB1 do not make a modified antigen, corresponding to MuB1, but are genetically deficient in synthetic ability at this site. By reaction with antibody to MuB1 an antigen corresponding to MuB1 was found in 13 of the 15 orders of mammals, and in 63 of 85 mammalian species tested, including man and guinea pig. The quantity of the antigen MuB1 is always greater in the serum of male than in the serum of female mice. The concentration of MuB1 increases with age; this increase is more marked in male than in female mice. By means of backcross experiments it was shown that the inheritance of MuB1 is unifactorial, is independent of the inheritance of the gamma globulin allotype MuA2, and is qualitatively independent of the sex of the parents. The antigen MuB1 is found in the euglobulin fraction of serum; it loses its ability to precipitate with antibody after heating at 56°C, but not after treatment with ammonia or hydrazine. By gel filtration, MuB1 is separated with a fraction containing molecules of molecular weight ≈ 150,000. An empirical correlation was observed between the presence or absence of MuB1 in the sera from inbred mice and the presence or absence of hemolytic complement (Hc), as measured by a test using a high concentration of rabbit hemolysin. In backcross experiments also, a correlation between hemolytic complement and the presence of MuB1 was demonstrated. As with MuB1, male mice had a higher hemolytic complement level than females. The particular component of complement which may be identical with MuB1 has not been identified

Reliability of an automatic classifier for brain enlarged perivascular spaces burden and comparison with human performance

pp. 1465-1481En el cerebro, los espacios perivasculares agrandados (PVS) se relacionan con la enfermedad de los vasos pequeños (SVD), mala cognición, inflamación e hipertensión. Proponemos un esquema totalmente automático que utiliza una máquina de vectores de soporte (SVM) para clasificar la carga de PVS en los ganglios basales (BG) como baja o alta. Evaluamos el rendimiento de tres tipos diferentes de descriptores extraídos de la región BG en imágenes de RMN ponderadas en T2: (I) estadísticas obtenidas de los coeficientes de la transformada de Wavelet, (II) patrones binarios locales y (III) bolsa de palabras visuales (BoW), descriptores basados en la caracterización de claves locales obtenidas de una rejilla densa con las características de transformación de la función de escala-invariante (SIFT). Cuando se utilizaron estos últimos, el SVM clasificador alcanzó la mejor precisión (81,16%). Lo obtenido del clasificador utilizando los descriptores del BoW se comparó con las calificaciones visuales realizadas por un neurorradiólogo experimentado (observador 1) y por un analista de imágenes entrenado (observador 2). El acuerdo y la correlación cruzada entre el clasificador y el observador 2 (κ = 0,67 (0,58 – 0,76)) fueron ligeramente más altos que entre el clasificador y el observador 1 (κ = 0,62 (0,53 – 0,72)) y entre ambos observadores (κ = 0,68 (0,61 – 0,75)). Por último, se construyeron tres modelos de regresión logística que utilizan variables clínicas como variable independiente y cada una de las clasificaciones de PVS como variable dependiente, para evaluar clínicamente lo significativas que resultan las predicciones del clasificador. El ajuste del modelo para el clasificador era bueno (área bajo la curva (AUC) valores: 0,93 (modelo 1), 0,90 (modelo 2) y 0,92 (modelo 3)) y un poco mejor (es decir, valores de AUC: 0,02 unidades superiores) que las del modelo para el observador 2. Estos resultados sugieren que, aunque se puede mejorar, un clasificador automático para evaluar la carga de PVS de la resonancia magnética del cerebro puede proporcionar resultados clínicamente significativos cercanos a los de un observador entrenado.S

Location prediction based on a sector snapshot for location-based services

In location-based services (LBSs), the service is provided based on the users' locations through location determination and mobility realization. Most of the current location prediction research is focused on generalized location models, where the geographic extent is divided into regular-shaped cells. These models are not suitable for certain LBSs where the objectives are to compute and present on-road services. Such techniques are the new Markov-based mobility prediction (NMMP) and prediction location model (PLM) that deal with inner cell structure and different levels of prediction, respectively. The NMMP and PLM techniques suffer from complex computation, accuracy rate regression, and insufficient accuracy. In this paper, a novel cell splitting algorithm is proposed. Also, a new prediction technique is introduced. The cell splitting is universal so it can be applied to all types of cells. Meanwhile, this algorithm is implemented to the Micro cell in parallel with the new prediction technique. The prediction technique, compared with two classic prediction techniques and the experimental results, show the effectiveness and robustness of the new splitting algorithm and prediction technique

Acting on incidental findings in research imaging

No abstract available

Management of incidental findings during imaging research in "healthy" volunteers: current UK practice

OBJECTIVES: Incidental findings (IF) are becoming increasingly common due to the proliferation of imaging research. IFs can be life-changing for “healthy” volunteers. This study examined variation in IF management in UK research studies of healthy volunteers, including comparison with ethical and legal guidelines, thus providing baseline data and informing future practice. METHODS: Questionnaire of participant background [medical/non-medical; radiologist/non-radiologist; years as principal investigator (PI)], type of research (involving children or not), institutional policy, volunteer information, radiologist involvement in reporting scans and IF disclosure mechanisms. Investigator's current and perceived “ideal” practice was examined. Participants were PIs performing imaging research of healthy volunteers approved by UK ethics committees (2006–2009). RESULTS: 63/146 (43%) surveys completed. 54/61 (88.5%) had site-specific guidelines. Information commonly provided to volunteers should IF be found: personal data (51/62; 82%), contingency plans (54/62; 87%) and disclosure to general practitioner (GP)/treating physician (47/62; 76%). PIs used different strategies for image review. Commonest: radiologist reports research scans only when researcher suspicious of IF [15/57 (26%) compared with 5/28 (16%) in ideal practice]. Commonest ideal reporting strategy: routine reporting by specialist radiologists [9/28 (29%) compared with 8/57 (14%) in current practice]. 49/56 (87.5%) have a standardised disclosure contingency plan, usually involving GP. PIs most commonly disclosed IFs to volunteers when judged relevant (27/58; 47%), most commonly face to face (22/54; 41%), by volunteer's GP (26/60; 43%). Background of PI influenced consent, reporting and disclosure practice. CONCLUSION: There is wide variation in handling IFs in UK imaging research. Much of the current practice contravenes the vague existing legal and ethical guidelines, and is unlikely to be in the best interests of volunteers or researchers