Deconstructing canine demodicosis

Los ácaros Demodex son habitantes normales de la piel de los mamíferos. Los mismos se han adaptado a vivir dentro de los folículos pilosos y las glándulas sebáceas de la piel de sus huéspedes mamíferos. La demodicosis puede ser definida como una enfermedad inflamatoria cutánea caracterizada por la presencia de una sobrepoblación de ácaros Demodex. Se considera que la respuesta inmunitaria celular es la responsable del control de la población de ácaros, mientras que los roles de las respuestas inmunitarias humoral e innata, son desconocidos. En los animales domésticos, la forma más grave de la demodicosis, la padecen los perros. En consecuencia, la demodicosis canina es la enfermedad más estudiada. Se han identificado dos especies de ácaros Demodex en perros: Demodex canis y Demodex injai; mientras se ha propuesto una tercera especie denominada Demodex cornei. Muchos estudios han tratado de documentar la prevalencia de ácaros Demodex en los perros sanos mediante diferentes métodos. En la presente tesis doctoral, se describe una técnica de reacción en cadena de la polimerasa (PCR) a tiempo real para detectar ADN de Demodex (secuencia del gen de la quitina sintetasa) en pelos de perros. Ésta técnica demostró la presencia de ácaros Demodex en porcentajes más altos que en los estudios anteriores, sugiriendo que los ácaros Demodex están presentes en todos los perros sanos independientemente de la edad, sexo, raza o pelaje. Además, la técnica demuestra que las poblaciones de Demodex están distribuidas a lo largo del cuerpo de los perro en pequeño número. Con el fin de establecer las relaciones filogenéticas entre las dos especies caninas y la propuesta tercera especie, amplificamos y secuenciamos un fragmento del ADN mitocondrial de la subunidad ribosomal 16S. El análisis filogenético demuestra que D. injai es una especie diferente de D. canis y que D. cornei es probablemente una variante morfológica de D. canis. Además, se desarrolló y estandarizó una técnica de PCR convencional para la detección específica de ADN de D. injai. Ésta técnica demostró que D. injai también es un habitante normal de la piel de algunos perros y que en la mayoría de los casos clínicos de demodicosis canina, la sobrepoblación de D. injai es infrecuente. Finalmente, con el fin de ampliar los conocimientos de la respuesta humoral en la demodicosis canina, obtuvimos un extracto antigénico crudo de D. canis y demostramos, mediante una técnica de Western-blot, la presencia de inmunoglobulinas G contra diversos antígenos de D. canis en el suero de perros sanos, de perros con demodicosis juvenil generalizada con o sin infección cutánea secundaria. En conclusión, ésta tesis doctoral demuestra que los ácaros Demodex son habitantes normales de la piel canina y que se distribuyen en pequeño número a lo largo del pelaje canino. Además, los ácaros D. canis deben ser considerados una especie diferente a ácaros D. injai y, los ácaros D. cornei, una variante morfológica del mismo. Por otro lado, los perros sanos y los perros con demodicosis juvenil generalizada presentan una respuesta humoral adquirida y anticuerpos dirigidos contra diversos antígenos proteicos de D. canis.It is considered that Demodex mites are normal inhabitants of the mammalian skin. They have been adapted to live inside skin hair follicles and sebaceous glands of mammalian hosts. Demodicosis can be defined as an inflammatory skin disease characterized by the presence of Demodex mite overpopulation. It is considered that the cellular immune response is responsible for the control of mite population, while the role of the humoral and innate immune responses remains unknown. In domestic animals, the most severe form of demodicosis occurs in dogs. Consequently, canine demodicosis is the most studied disease produced by Demodex mites. Two canine Demodex species have been identified: Demodex canis, and Demodex injai, while a third species unofficially named Demodex cornei, has been proposed. Many studies have tried to report Demodex prevalence in healthy dogs by different methods. In the present doctoral thesis, we described a real-time PCR technique to detect Demodex DNA (sequence of chitin synthase gene) in canine hair samples. This technique demonstrated the presence of Demodex mites in higher percentages than previous reports, suggesting that Demodex mites are present in all healthy dogs independent of age, sex, breed, or coat. Furthermore, Demodex populations were distributed in small numbers along the dog's body. In order to analyze the phylogenetic relationships between the two canine Demodex species and the proposed third species, we amplified and sequenced a fragment of the mitochondrial 16S rDNA gene. Phylogenetic analysis revealed that D. injai is a different species from D. canis. In addition, it demonstrated that D. cornei is probably a morphological variant of D. canis. A conventional PCR for the specific detection of D. injai DNA was also developed and standardized. This technique demonstrated that D. injai is also a normal inhabitant of some dogs. Moreover, it suggested that in the majority of clinical canine demodicosis cases, an overgrowth of D. injai is unlikely. Finally, to enlighten the field of the humoral response in canine demodicosis, a D. canis crude extract antigen was obtained and we demonstrated the presence of immunoglobulins G against several D. canis antigens in the sera of healthy dogs and in the sera of dogs with juvenile generalized demodicosis with and without secondary complicating pyoderma by western blot technique. In conclusion, this doctoral thesis demonstrated that Demodex mites are normal inhabitant of the canine skin, they are present in the majority of dogs, and are distributed in very low numbers along all the haired skin. Furthermore, Demodex injai must be considered a different species from D. canis, and D. cornei is a probable morphological variant of D. canis. Healthy dogs and dogs with canine juvenile generalized demodicosis have an acquired humoral immune response against Demodex mites and present serum antibodies directed against several Demodex canis protein antigens

Notulae to the Italian flora of algae, bryophytes, fungi and lichens: 2

In this contribution, new data concerning red algae, lichens and bryophytes of the Italian flora are presented. It includes new records and confirmations for the algal genus Grateloupia, the bryophyte genus Didymodon, and the lichen genera Buellia, Cladonia, Letharia, Pertusaria, and Pyrenula

Evaluar para aprender: un proceso de investigación-acción en la carrera de Bioingeniería

La evaluación del aprendizaje es una problemática que despierta inquietudes en la comunidad universitaria. Numerosas investigaciones indican que los sistemas de evaluación implementados por los docentes influyen fuertemente en el proceso de aprendizaje. Estos resultados, y la polémica que despiertan, hacen visible la necesidad de repensar la evaluación atendiendo a su complejidad, su vinculación con el proceso de enseñanza y su fuerte impacto en el proceso de aprendizaje. Esta situación motivó la formulación de este proyecto enmarcado en los principios metodológicos de una Investigación-Acción, el cual se propuso describir y analizar críticamente el proceso de evaluación en “Cálculo Vectorial” y “Ecuaciones Diferenciales”, asignaturas de la carrera de Bioingeniería. Como resultado de las acciones implementadas se realizaron diferentes modificaciones en las prácticas de enseñanza y de evaluación, encuadradas en un nuevo plan de evaluación con enfoque formativo, y se generó en los docentes un proceso altamente reflexivo sobre esos cambios. A partir de esta I-A se ha iniciado un proceso de cambio en la manera de pensar la evaluación, no ha sido sencillo modificar las tradiciones que impregnan la evaluación en carreras de ingeniería, vencer estas resistencias ha sido posible a través de un trabajo colaborativo sostenido en el tiempo

The Athena X-ray Integral Field Unit (X-IFU)

The X-ray Integral Field Unit (X-IFU) is the high resolution X-ray spectrometer of the ESA Athena X-ray observatory. Over a field of view of 5' equivalent diameter, it will deliver X-ray spectra from 0.2 to 12 keV with a spectral resolution of 2.5 eV up to 7 keV on similar to 5 '' pixels. The X-IFU is based on a large format array of super-conducting molybdenum-gold Transition Edge Sensors cooled at similar to 90 mK, each coupled with an absorber made of gold and bismuth with a pitch of 249 mu m. A cryogenic anti-coincidence detector located underneath the prime TES array enables the non X-ray background to be reduced. A bath temperature of similar to 50 mK is obtained by a series of mechanical coolers combining 15K Pulse Tubes, 4K and 2K Joule-Thomson coolers which pre-cool a sub Kelvin cooler made of a He-3 sorption cooler coupled with an Adiabatic Demagnetization Refrigerator. Frequency domain multiplexing enables to read out 40 pixels in one single channel. A photon interacting with an absorber leads to a current pulse, amplified by the readout electronics and whose shape is reconstructed on board to recover its energy with high accuracy. The defocusing capability offered by the Athena movable mirror assembly enables the X-IFU to observe the brightest X-ray sources of the sky (up to Crab-like intensities) by spreading the telescope point spread function over hundreds of pixels. Thus the X-IFU delivers low pile-up, high throughput (> 50%), and typically 10 eV spectral resolution at 1 Crab intensities, i.e. a factor of 10 or more better than Silicon based X-ray detectors. In this paper, the current X-IFU baseline is presented, together with an assessment of its anticipated performance in terms of spectral resolution, background, and count rate capability. The X-IFU baseline configuration will be subject to a preliminary requirement review that is scheduled at the end of 2018. The X-IFU will be provided by an international consortium led by France, the Netherlands and Italy, with further ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Ireland, Poland, Spain, Switzerland and contributions from Japan and the United States.Peer reviewe

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV