Rapport sur les réseaux grands débits et l\u27entrée dans la société de l\u27information

Rapport de l\u27 Office parlementaire d\u27évaluation des choix scientifiques et technologiques sur la situation des nouvelles technologies de l\u27information et de la communication en France et sur les stratégies politiques à développer pour l\u27entrée dans la société de l\u27information

Papel del inmunoproteosoma en enfermedades neurodegenerativas y cáncer

Los avances científicos y la constante evolución de los métodos de experimentación han permitido conocer la gran importancia que tiene el proteosoma en nuestro organismo. Este complejo intracelular, capaz de degradar proteínas una vez señalizadas, ha demostrado ser un importante actor en diferentes enfermedades, debido a que su mal funcionamiento puede acarrear desequilibrios proteicos, con diferentes e importantes consecuencias. Así, se ha probado que una sobreexpresión del mismo, conduce a una degradación excesiva de ciertas proteínas, sobre todo aquellas de tiempo de vida corto, modificando así el curso normal del ciclo celular. Esto tendría como consecuencias una proliferación descontrolada de células, o una inhibición de la muerte celular. Todas estas modificaciones en las concentraciones plasmáticas de determinadas proteínas, pueden desembocar finalmente en un proceso oncológico. Es así como ha surgido una nueva familia de fármacos anticancerosos, los inhibidores del proteosoma, capaces de frenar dicho proceso patológico. También se sospecha, que la baja actividad del mismo puede disminuir la degradación de proteínas, y provocar un aumento de concentración de estas, tanto en el interior como en el exterior celular. En ocasiones, estas proteínas estarán mal plegadas o defectuosas, y se formarán agregados proteicos, que puede provocar un mal funcionamiento celular. Este sería el caso de las enfermedades neurodegenerativas. Muchas de estas patologías se caracterizan por la presencia de conjugados proteicos, como los ovillos neurofibrilares en Alzheimer, los cuerpos de Lewys en el tronco cerebral en pacientes con Parkinson, agregados de huntingtina en la enfermedad de Huntington, o cuerpos de bunina en la Esclerosis Lateral Amiotrófica. Por otro lado, tanto el cáncer como las enfermedades neurodegenerativas se acompañan de procesos inflamatorios, que pueden afectar a la homeostasis proteica, alterando el tipo y la cantidad de proteosomasUniversidad de Sevilla. Grado en Farmaci

Structure-properties relationships in triarylamine-based donor-acceptor molecules containing naphtyl groups as donor material for organic solar cells

The effects of replacing the phenyl rings of triphenylamine (TPA) by naphtyl groups are analysed on a series of push-pull molecules containing a 2-thienyl-dicyanovinyl acceptor group. UV-Vis absorption spectroscopy and cyclic voltammetry show that the introduction of one or two naphtyl groups in the structure has limited effects on the optical properties and energy levels of the molecule. On the other hand, the evaluation of the compounds as donor material in bi-layer solar cells with C60 as acceptor shows that the number and mode of linkage of the naphtyl groups exert a marked influence on the power conversion efficiency (PCE) of the cell. Two naphtyl groups lead to a decrease of PCE with respect to TPA, while a single naphtyl group produces opposite effects depending on the linking mode. Compared to TPA, an alpha-naphtyl group leads to a small decrease of PCE while in contrast a beta-naphtyl leads to a ~35% increase of PCE due to improved short-circuit current density (Jsc) and fill-factor. The determination of the hole-mobility of these two donors by the space-charge-limited current method shows that these effects are correlated with the higher hole-mobility of the β-naphtyl compound

Osteomalacia in a patient with Paget's bone disease treated with long-term etidronate

SummaryA 93 year-old woman with Paget\u27s disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5 mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget\u27s disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated

Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Estimation of cost-of-illness in patients with psoriasis in Switzerland

BACKGROUND: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. METHODS: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. RESULTS: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. CONCLUSIONS: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control

Final Research Report on Auto-Tagging of Music

The deliverable D4.7 concerns the work achieved by IRCAM until M36 for the “auto-tagging of music”. The deliverable is a research report. The software libraries resulting from the research have been integrated into Fincons/HearDis! Music Library Manager or are used by TU Berlin. The final software libraries are described in D4.5. The research work on auto-tagging has concentrated on four aspects: 1) Further improving IRCAM’s machine-learning system ircamclass. This has been done by developing the new MASSS audio features, including audio augmentation and audio segmentation into ircamclass. The system has then been applied to train HearDis! “soft” features (Vocals-1, Vocals-2, Pop-Appeal, Intensity, Instrumentation, Timbre, Genre, Style). This is described in Part 3. 2) Developing two sets of “hard” features (i.e. related to musical or musicological concepts) as specified by HearDis! (for integration into Fincons/HearDis! Music Library Manager) and TU Berlin (as input for the prediction model of the GMBI attributes). Such features are either derived from previously estimated higher-level concepts (such as structure, key or succession of chords) or by developing new signal processing algorithm (such as HPSS) or main melody estimation. This is described in Part 4. 3) Developing audio features to characterize the audio quality of a music track. The goal is to describe the quality of the audio independently of its apparent encoding. This is then used to estimate audio degradation or music decade. This is to be used to ensure that playlists contain tracks with similar audio quality. This is described in Part 5. 4) Developing innovative algorithms to extract specific audio features to improve music mixes. So far, innovative techniques (based on various Blind Audio Source Separation algorithms and Convolutional Neural Network) have been developed for singing voice separation, singing voice segmentation, music structure boundaries estimation, and DJ cue-region estimation. This is described in Part 6.EC/H2020/688122/EU/Artist-to-Business-to-Business-to-Consumer Audio Branding System/ABC D

Interleukin 23-Helper T Cell 17 Axis as a Treatment Target for Pityriasis Rubra Pilaris.

Treatment of pityriasis rubra pilaris (PRP) is solely based on its resemblance to psoriasis rather than any knowledge of its pathomechanism. Insight into pathogenic mediators of inflammation is essential for targeted and valid treatment options that could replace previous serendipitous therapeutic approaches in refractory PRP. To determine whether blockade of the interleukin 23-helper T cell 17 (IL-23-TH17) pathway with ustekinumab represents an efficacious and, based on its proinflammatory cytokine profile, targeted treatment option in PRP. In this case report, a patient with PRP received outpatient treatment at a university hospital department of dermatology with ustekinumab according to the dosing regimen approved for psoriasis. Lesional skin biopsy samples were taken from this patient and 2 others with refractory PRP. Messenger RNA (mRNA) expression of proinflammatory innate and T-cell-derived cytokines were measured and compared with skin samples from patients with psoriasis and healthy donors. From 1 patient, lesional skin samples were taken before ustekinumab treatment and 4 and 28 weeks after treatment initiation. Follow-up was completed after 6 months. Subcutaneous ustekinumab, 45 mg, at weeks 0 and 4 and quarterly thereafter. The primary outcome was to determine the changes in expression of proinflammatory innate and T-cell-derived cytokines during ustekinumab therapy. The secondary objective was to evaluate the clinical and histopathologic phenotype in relation to the mRNA expression profile of proinflammatory cytokines. In lesional PRP skin samples from a single patient, upregulated expression levels were found for most proinflammatory innate cytokines, including tumor necrosis factor (TNF), IL-6, IL-12, IL-23, and IL-1β. Among adaptive T-cell cytokines, an increase of TH1 cytokines and, in particular, TH17 cytokines IL-17A, IL-17F, and IL-22 was seen in PRP. The patient with PRP who received ustekinumab showed regression of skin lesions after 2 weeks and almost complete resolution after 1 month. Clinical and histopathologic improvement paralleled the expression levels of TH17 cytokines but not of interferon-γ and TNF, which lagged behind the amelioration. In this case report, a role of the IL-23-TH17-axis in PRP was identified, suggesting a shared pathogenic inflammatory pathway with psoriasis, despite evident clinical and histopathologic differences. In addition, this report provides a rationale for targeting the IL-23-TH17-pathway as a treatment option for refractory PRP