Utility of early circulating tumour DNA dynamics as a surrogate for progression free survival in the BEECH phase I/II trial in metastatic breast cancer

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Quality of life in hidradenitis suppurativa : Validation of the hsqol-24

Altres ajuts: reports grants, personal fees, non-financial support and other from Abbvie, Almirall, Amgen, Boehringer, Celgene, Janssen-Cilag, Leo Pharma, Lilly, MSD-Schering-Plough, Novartis, Pfizer and UCB, outside the submitted work. TGC reports personal fees from Lilly and Novartis, outside the submitted work. LP reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Leo-Pharma, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, personal fees from Baxalta, Biogen, Fresenius-Kabi, JS Biocad, Mylan, Sandoz, Samsung-Bioepis, and Bristol Myers Squibb, outside the submitted work. The other authors have no conflicts of interest to declare.To date, there are no disease-specific instruments in Spanish to assess quality of life of patients with hidra-denitis suppurativa. A multicentre study was pre-viously carried out in Spain between 2016 and 2017 to develop the Hidradenitis Suppurativa Quality of Life-24 (HSQoL-24), a disease-specific questionnaire to assess quality of life in patients with hidradenitis suppurativa. The objectives of this study are to revali-date the HSQoL-24 in Spanish with a larger sample of patients, and to present the English version. In this multi centre study in Spain, patients with hidradenitis suppurativa completed the HSQoL-24, the Dermatology Life Quality Index and the Skindex-29. The Hurley staging system was used to assess the severity of the disease. Validation of the questionnaire was carried out in 130 patients, of whom 75 (57.7%) were women. This study demonstrates adequate values of reliability and validity of the HSQoL-24, confirming the previous test re-test validation and making this questionnaire one of wide clinical validity in terms of results perceiv-ed by patients

Análisis de la utilización de antihistamínicos sistémicos según criterios de calidad

Objetivos: El objetivo primario del presente trabajo es analizar el uso racional de los antihistamínicos H1 en nuestro entorno. Para ello, se pretende valorar la utilización bajo prescripción médica de antihistamínicos H1 sistémicos en pacientes con alergias, analizando si la selección se adecua a las guías clínicas, los fármacos asociados y la percepción de efectividad del tratamiento con distintos antihistamínicos, así como a los indicadores de calidad de prescripción. Métodos: Estudio observacional y transversal de 94 encuestas realizadas a pacientes (EP) de diferentes ámbitos asistenciales en tratamiento con antihistamínicos H1 sistémicos, que se complementa con el análisis de ventas de antihistamínicos en farmacias (VFC) mediante un estudio observacional y retrospectivo de las dispensaciones en 4 farmacias comunitarias de la Comunidad Valenciana (datos de 2010). Resultados: Ebastina es el fármaco más prescrito (34% VFC y 27% EP), destacando la venta de preparados bucodispersables (flas) que suponen la mitad del gasto en este fármaco. Cetirizina es el segundo fármaco en cuota de mercado (16% VFC y 18% EP). Los nuevos derivados, desloratadina y levocetirizina, representan el 14 y el 12% de las VFC, y el 10 y el 17% de las EP, respectivamente, valores superiores al fármaco de primera elección, loratadina (7% VFC y 4% EP). El indicador de prescripción de loratadina + cetirizina (fármacos recomendados por diversas guías terapéuticas) es de 0,2, valor inferior al mínimo deseable (0,4) según criterios de calidad. Conclusiones: La prescripción de antihistamínicos sistémicos no sigue criterios de selección racional. La escasa utilización de loratadina y cetirizina incrementa el gasto farmacéutico, ya que su coste medio por envase (3,20 euros) es inferior al del resto de antihistamínicos (10,20 euros). Existe un campo de mejora para controlar el gasto farmacéutico mediante la promoción del uso de los antihistamínicos más eficientes

Análisis de la utilización de antihistamínicos sistémicos según criterios de calidad

Objetivos: El objetivo primario del presente trabajo es analizar el uso racional de los antihistamínicos H1 en nuestro entorno. Para ello, se pretende valorar la utilización bajo prescripción médica de antihistamínicos H1 sistémicos en pacientes con alergias, analizando si la selección se adecua a las guías clínicas, los fármacos asociados y la percepción de efectividad del tratamiento con distintos antihistamínicos, así como a los indicadores de calidad de prescripción. Métodos: Estudio observacional y transversal de 94 encuestas realizadas a pacientes (EP) de diferentes ámbitos asistenciales en tratamiento con antihistamínicos H1 sistémicos, que se complementa con el análisis de ventas de antihistamínicos en farmacias (VFC) mediante un estudio observacional y retrospectivo de las dispensaciones en 4 farmacias comunitarias de la Comunidad Valenciana (datos de 2010). Resultados: Ebastina es el fármaco más prescrito (34% VFC y 27% EP), destacando la venta de preparados bucodispersables (flas) que suponen la mitad del gasto en este fármaco. Cetirizina es el segundo fármaco en cuota de mercado (16% VFC y 18% EP). Los nuevos derivados, desloratadina y levocetirizina, representan el 14 y el 12% de las VFC, y el 10 y el 17% de las EP, respectivamente, valores superiores al fármaco de primera elección, loratadina (7% VFC y 4% EP). El indicador de prescripción de loratadina + cetirizina (fármacos recomendados por diversas guías terapéuticas) es de 0,2, valor inferior al mínimo deseable (0,4) según criterios de calidad. Conclusiones: La prescripción de antihistamínicos sistémicos no sigue criterios de selección racional. La escasa utilización de loratadina y cetirizina incrementa el gasto farmacéutico, ya que su coste medio por envase (3,20 euros) es inferior al del resto de antihistamínicos (10,20 euros). Existe un campo de mejora para controlar el gasto farmacéutico mediante la promoción del uso de los antihistamínicos más eficientes

β-delayed γ-proton decay in 56Zn: analysis of the charged-particle spectrum

A study of the beta decay of the proton-rich T-z = 2 nucleus Zn-56 has been reported in a recent publication. A rare and exotic decay mode, beta-delayed gamma-proton decay, has been observed there for the first time in the fp shell. Here, we expand on some of the details of the data analysis, focussing on the charged particle spectrum

Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum

[EN] Fusarium circinatum is a harmful pathogenic fungus mostly attacking Pinus species and also Pseudotsuga menziesii, causing cankers in trees of all ages, damping-off in seedlings, and mortality in cuttings and mother plants for clonal production. This fungus is listed as a quarantine pest in several parts of the world and the trade of potentially contaminated pine material such as cuttings, seedlings or seeds is restricted in order to prevent its spread to disease-free areas. Inspection of plant material often relies on DNA testing and several conventional or real-time PCR based tests targeting F. circinatum are available in the literature. In this work, an international collaborative study joined 23 partners to assess the transferability and the performance of nine molecular protocols, using a wide panel of DNA from 71 representative strains of F. circinatum and related Fusarium species. Diagnostic sensitivity, specificity and accuracy of the nine protocols all reached values >80%, and the diagnostic specificity was the only parameter differing significantly between protocols. The rates of false positives and of false negatives were computed and only the false positive rates differed significantly, ranging from 3.0% to 17.3%. The difference between protocols for some of the performance values were mainly due to cross-reactions with DNA from non-target species, which were either not tested or documented in the original articles. Considering that participating laboratories were free to use their own reagents and equipment, this study demonstrated that the diagnostic protocols for F. circinatum were not easily transferable to end-users. More generally, our results suggest that the use of protocols using conventional or real-time PCR outside their initial development and validation conditions should require careful characterization of the performance data prior to use under modified conditions (i.e. reagents and equipment). Suggestions to improve the transfer are proposed.This work was supported by COST action FP1406 Pinestrength . The work of the Estonian team was supported by the Estonian Science Foundation grants PSG136 and IUT21-04. The work of Portuguese team from INIAV was financed by INIAV I.P. Institute. The work at U. Aveiro (Portugal) was financed by European Funds through COMPETE and National Funds through the Portuguese Foundation for Science and Technology (FCT) to CESAM (UID/AMB/50017/2013 POCI-01- 0145-FEDER-007638). The work of Slovenian team was financed through Slovenian Research Agency (P4-0107) and by the Slovenian Ministry of Agriculture, Forestry and Food (Public Forestry Service). The British work was financially supported by the Forestry Commission, UK. The French work was financially supported by the French Agency for Food, environmental and occupational health safety (ANSES). The work in New Zealand was funded by Operational Research Programmes, Ministry for Primary Industries, New Zealand.Ioos, R.; Aloi, F.; Piskur, B.; Guinet, C.; Mullett, M.; Berbegal Martinez, M.; Bragança, H.... (2019). Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum. Scientific Reports. 9:1-17. https://doi.org/10.1038/s41598-019-44672-8S1179Schmale, D. G. III & Gordon, T. R. Variation in susceptibility to pitch canker disease, caused by Fusarium circinatum, in native stands of Pinus muricata. Plant Pathol. 52, 720–725 (2003).Gordon, T. R., Kirkpatrick, S. C., Aegerter, B. J., Wood, D. L. & Storer, A. J. Susceptibility of Douglas fir (Pseudotsuga menziesii) to pitch canker, caused by Gibberella circinata (anamorph = Fusarium circinatum). Plant Pathol. 55, 231–237 (2006).Martínez‐Álvarez, P., Pando, V. & Diez, J. J. Alternative species to replace Monterey pine plantations affected by pitch canker caused by Fusarium circinatum in northern Spain. Plant Pathol. 63, 1086–1094, https://doi.org/10.1111/ppa.12187 (2014).Wingfield, M. J. et al. Pitch canker caused by Fusarium circinatum - a growing threat to pine plantations and forests worldwide. Australas. Plant Path. 37, 319–334 (2008).Bezos, D., Martinez-Alvarez, P., Fernandez, M. & Diez, J. J. Epidemiology and management of pine pitch canker disease in Europe - a review. Balt. For. 23, 279–293 (2017).Landeras, E. et al. Outbreak of pitch canker caused by Fusarium circinatum on Pinus spp. in Northern Spain. Plant Dis. 89, 1015 (2005).Bragança, H., Diogo, E., Moniz, F. & Amaro, P. First report of pitch canker on pines caused by Fusarium circinatum in Portugal. Plant Dis. 93, 1079–1079, https://doi.org/10.1094/PDIS-93-10-1079A (2009).EFSA. Risk assessment of Gibberella circinata for the EU territory and identification and evaluation of risk management options. EFSA Journal 8, 1620 (2010).Carlucci, A., Colatruglio, L. & Frisullo, S. First report of pitch canker caused by Fusarium circinatum on Pinus halepensis and P. pinea in Apulia (Southern Italy). Plant Dis. 91, 1683 (2007).Vettraino, A., Potting, R. & Raposo, R. EU legislation on forest plant health: an overview with a focus on Fusarium circinatum. Forests 9, 568 (2018).Möykkynen, T., Capretti, P. & Pukkala, T. Modelling the potential spread of Fusarium circinatum, the causal agent of pitch canker in Europe. Annals of Forest Sciences 72, 169–181 (2015).Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55, https://doi.org/10.1373/clinchem.2008.112797 (2009).EPPO. PM 7/91(1): Gibberella circinata. EPPO Bull. 39, 298–309 (2009).ISTA. 7-009: Detection of Gibberella circinata on Pinus spp. (pine) and Pseudotsuga menziesii (Douglas-fir) seed. Validated Seed Health Testing Methods (2015).IPPC. ISPM 27, Diagnostic protocols for regulated pests, DP 22: Fusarium circinatum (2017).EPPO. PM 7/98 (2) Specific requirements for laboratories preparing accreditation for a plant pest diagnostic activity. EPPO Bull. 44, 117–147, https://doi.org/10.1111/epp.12118 (2014).Nirenberg, H. I. & O’Donnell, K. New Fusarium species and combinations within the Gibberella fujikuroi species complex. Mycologia 90, 434–458 (1998).Britz, H., Coutinho, T. A., Wingfield, M. J. & Marasas, W. F. O. Validation of the description of Gibberella circinata and morphological differentiation of the anamorph Fusarium circinatum. Sydowia 54, 9–22 (2002).Mullett, M., Pérez-Sierra, A., Armengol, J. & Berbegal, M. Phenotypical and molecular characterisation of Fusarium circinatum: correlation with virulence and fungicide sensitivity. Forests 8, 458 (2017).Herron, D. A. et al. Novel taxa in the Fusarium fujikuroi species complex from Pinus spp. Stud. Mycol. 80, 131–150, https://doi.org/10.1016/j.simyco.2014.12.001 (2015).Storer, G. & Clark, S. L. Association of the pitch canker fungus, Fusarium subglutinans f.sp. pini, with Monterey pine seeds and seedlings in California. Plant Pathol. 47, 649–656, https://doi.org/10.1046/j.1365-3059.1998.00288.x (1998).Schweigkofler, W., O’Donnell, K. & Garbelotto, M. Detection and quantification of airborne conidia of Fusarium circinatum, the causal agent of pine pitch canker, from two California sites by using a real-time PCR approach combined with a simple spore trapping method. Appl. Environ. Microbiol. 70, 3512–3520 (2004).Ramsfield, T. D., Dobbie, K., Dick, M. A. & Ball, R. D. Polymerase chain reaction-based detection of Fusarium circinatum, the causal agent of pitch canker disease. Molecular Ecology Resources 8, 1270–1273 (2008).Ioos, R., Fourrier, C., Iancu, G. & Gordon, T. R. Sensitive Detection of Fusarium circinatum in Pine Seed by Combining an Enrichment Procedure with a Real-Time Polymerase Chain Reaction Using Dual-Labeled Probe Chemistry. Phytopathology 99, 582–590, https://doi.org/10.1094/PHYTO-99-5-0582 (2009).Dreaden, T. J., Smith, J. A., Barnard, E. L. & Blakeslee, G. Development and evaluation of a real-time PCR seed lot screening method for Fusarium circinatum, causal agent of pitch canker disease. For. Path. 42, 405–411, https://doi.org/10.1111/j.1439-0329.2012.00774.x (2012).Fourie, G. et al. Culture-independent detection and quantification of Fusarium circinatum in a pine-producing seedling nursery. Southern Forests: a Journal of Forest Science 76, 137–143, https://doi.org/10.2989/20702620.2014.899058 (2014).Lamarche, J. et al. Molecular detection of 10 of the most unwanted alien forest pathogens in Canada using Real-Time PCR. PLoS ONE 10, e0134265, https://doi.org/10.1371/journal.pone.0134265 (2015).Luchi, N., Pepori, A. L., Bartolini, P., Ioos, R. & Santini, A. Duplex real-time PCR assay for the simultaneous detection of Caliciopsis pinea and Fusarium circinatum in pine samples. Applied Microbiology and Biotechnology 102, 7135–7146, https://doi.org/10.1007/s00253-018-9184-1 (2018).Sandoval-Denis, M., Swart, W. J. & Crous, P. W. New Fusarium species from the Kruger National Park, South Africa. MycoKeys 34, https://doi.org/10.3897/mycokeys.34.25974 (2018).Steenkamp, E. T., Wingfield, B. D., Desjardins, A. E., Marasas, W. F. & Wingfield, M. J. Cryptic speciation in Fusarium subglutinans. Mycologia 94, 1032–1043 (2002).Garcia-Benitez, C. et al. Proficiency of real-time PCR detection of latent Monilinia spp. infection in nectarine flowers and fruit. Phytopathologia Mediterranea 56, 242–250 (2017).Ebentier, D. L. et al. Evaluation of the repeatability and reproducibility of a suite of qPCR-based microbial source tracking methods. Water Research 47, 6839–6848, https://doi.org/10.1016/j.watres.2013.01.060 (2013).Bustin, S. & Huggett, J. qPCR primer design revisited. Biomolecular Detection and Quantification 14, 19–28, https://doi.org/10.1016/j.bdq.2017.11.001 (2017).Grosdidier, M., Aguayo, J., Marçais, B. & Ioos, R. Detection of plant pathogens using real-time PCR: how reliable are late Ct values? Plant Pathol. 66, 359–367, https://doi.org/10.1111/ppa.12591 (2017).Al-Soud, W. A. & Rådström, P. Capacity of nine thermostable DNA polymerases to mediate DNA amplification in the presence of PCR-inhibiting samples. Applied and environmental microbiology 64, 3748–3753 (1998).Saunders, G. C., Dukes, J., Parkes, H. C. & Cornett, J. H. Interlaboratory study on thermal cycler performance in controlled PCR and random amplified polymorphic DNA analyses. Clinical chemistry 47, 47–55 (2001).Boutigny, A.-L. et al. Optimization of a real-time PCR assay for the detection of the quarantine pathogen Melampsora medusae f. sp. deltoidae. Fungal Biology 117, 389–398, https://doi.org/10.1016/j.funbio.2013.04.001 (2013).Guinet, C., Fourrier-Jeandel, C., Cerf-Wendling, I. & Ioos, R. One-step detection of Monilinia fructicola, M. fructigena, and M. laxa on Prunus and Malus by a multiplex real-time PCR assay. Plant Dis. 100, 2465–2474, https://doi.org/10.1094/PDIS-05-16-0655-RE (2016).Aguayo, J. et al. Development of a hydrolysis probe-based real-time assay for the detection of tropical strains of Fusarium oxysporum f. sp. cubense race 4. PLoS ONE 12, e0171767, https://doi.org/10.1371/journal.pone.0171767 (2017).Broeders, S. et al. Guidelines for validation of qualitative real-time PCR methods. Trends in Food Science & Technology 37, 115–126, https://doi.org/10.1016/j.tifs.2014.03.008 (2014).Pelloux, H. et al. A second European collaborative study on polymerase chain reaction for Toxoplasma gondii, involving 15 teams. FEMS Microbiology Letters 165, 231–237, https://doi.org/10.1111/j.1574-6968.1998.tb13151.x (1998).Leslie, J. F. & Summerell, B. A. The Fusarium laboratory manual. (Blackwell Publishing, 2006).Ioos, R. et al. Test performance study of diagnostic procedures for identification and detection of Gibberella circinata in pine seeds in the framework of a EUPHRESCO project. EPPO Bull. 43, 267–275, https://doi.org/10.1111/epp.12037 (2013).Geiser, D. M. FUSARIUM-ID v. 1.0: a DNA sequence database for identifying Fusarium. Eur. J. Plant Pathol. 110, 473–479 (2004).White, T. J., Bruns, T., Lee, S. & Taylor, J. In PCR protocols: a guide to method and applications (eds Gelfand, D. H., Innis M. A., Sninsky, J. J. and White, T. J.) 315–322 (Academic Press, 1990).Nirenberg, H. I. A simplified method for identifying Fusarium spp. occurring on wheat. Canadian Journal of Botany 59, 1599–1609 (1981).Chabirand, A., Loiseau, M., Renaudin, I. & Poliakoff, F. Data processing of qualitative results from an interlaboratory comparison for the detection of “Flavescence dorée” phytoplasma: How the use of statistics can improve the reliability of the method validation process in plant pathology. PLoS ONE 12, e0175247, https://doi.org/10.1371/journal.pone.0175247 (2017).Loreti, S. et al. Performance of diagnostic tests for the detection and identification of Pseudomonas syringae pv. actinidiae (Psa) from woody samples. European Journal of Plant Pathology, https://doi.org/10.1007/s10658-018-1509-5 (2018).International Standardization Organization. ISO 16140:2003 Microbiology of food and animal feeding stuffs - Protocol for the validation of alternative methods (2003).Langton, S., Chevennement, R., Nagelkerke, N. & Lombard, B. Analysing collaborative trials for qualitative microbiological methods: accordance and concordance. International Journal of Food Microbiology 79, 175–181 (2002).R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna (2014). R Foundation for Statistical Computing (2017).Wickham, H. ggplot2 : elegant graphics for data analysis. (Springer, 2016)

Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (−dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy

Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio

The exposure of the hybrid detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays. It consists of a surface array to measure secondary particles at ground level and a fluorescence detector to measure the development of air showers in the atmosphere above the array. The "hybrid" detection mode combines the information from the two subsystems. We describe the determination of the hybrid exposure for events observed by the fluorescence telescopes in coincidence with at least one water-Cherenkov detector of the surface array. A detailed knowledge of the time dependence of the detection operations is crucial for an accurate evaluation of the exposure. We discuss the relevance of monitoring data collected during operations, such as the status of the fluorescence detector, background light and atmospheric conditions, that are used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic