33 research outputs found

    Automated Design and Optimization of Metallic Alloys

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    The design and optimization of metallic alloys poses a significant engineering challenge. The search space of all possible alloys is sufficiently large that it is impossible to fully explore by traditional methods. In order to address this challenge, physics based computational frameworks linked to advanced machine learning algorithms can serve to automate this process with computational efficiency such that the state of the industry may be rapidly advanced. The work herein presents a suite of computational frameworks leveraged to automate the design and optimization process of advanced alloys. An ab initio alloy thermodynamics system, Molecular Dynamics simulations, a Convolutional-Neural Network system, and a coupled Neural Network and Multi-objective Genetic Algorithm. These algorithms are validated over the set of binary nanocrystalline Al-X alloys, and multi-component High Entropy Alloys (HEA)

    Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial

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    Place de la laparoscopie dans le traitement du cancer de l'endomètre

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    Les récents progrès de la laparoscopie ont modifié l'approche chirurgicale des patientes atteintes d'un cancer de l'endomètre. Le centre Swissendos Fribourg en collaboration avec l'AGO (Groupe de travail pour la gynécologie oncologique) et l'AGE (Groupe de travail pour la gynécologie endoscopique) ont entrepris d'élaborer un consensus basé sur l'évidence pour la pratique de la laparoscopie dans le traitement du cancer de l'endomètre. L'objectif a été de définir une approche propre à la Suisse en fournissant aux praticiens une aide à la prise en charge. = Recent advance in laparoscopy have changed the surgical approach of endometrial cancer patients. The Swissendos Center, Fribourg, in collaboration with AGO (Groupe de travail pour la gynécologie oncologique) and AGE (groupe de travail pour la gynécologie endoscopique) have established a consensus based on the available evidence for the use of laparoscopy in the management of patients with endometrial cancer The main objective was to define Swiss clinical practice guidelines appropriate to the country and consistent with the needs of the physicians

    Pharmacological inhibition of acetylcholine-regulated potassium current (I K,ACh) prevents atrial arrhythmogenic changes in a rat model of repetitive obstructive respiratory events

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    BACKGROUND: In obstructive sleep apnea (OSA), intermittent hypoxemia and intrathoracic pressure fluctuations may increase atrial fibrillation (AF) susceptibility by cholinergic activation. OBJECTIVE: To investigate short-term atrial electrophysiological consequences of obstructive respiratory events, simulated by intermittent negative upper airway pressure (INAP), and the role of atrial acetylcholine-regulated potassium current (I(K,ACh)) activated by the M(2) receptor. METHODS: In sedated (2% isoflurane), spontaneously breathing rats, INAP was applied noninvasively by a negative pressure device for 1 minute, followed by a resting period of 4 minutes. INAP was applied repeatedly throughout 70 minutes, followed by a 2-hour recovery period. Atrial effective refractory period (AERP) and AF inducibility were determined throughout the protocol. To study INAP-induced I(K,ACh) activation, protein levels of protein kinase C (PKC(Ɛ)) were determined in membrane and cytosolic fractions of left atrial (LA) tissue by Western blotting. Moreover, an I(K,ACh) inhibitor (XAF-1407: 1 mg/kg) and a muscarinic receptor inhibitor (atropine: 1 μg/kg) were investigated. RESULTS: In vehicle-treated rats, repetitive INAP shortened AERP (37 ± 3 ms vs baseline 44 ± 3 ms; P = .001) and increased LA membrane PKC(Ɛ) content relative to cytosolic levels. Upon INAP recovery, ratio of PKC(Ɛ) membrane to cytosol content normalized and INAP-induced AERP shortening reversed. Both XAF-1407 and atropine increased baseline AERP (control vs XAF-1407: 61 ± 4 ms; P > .001 and control vs atropine: 58 ± 3 ms; P = .011) and abolished INAP-associated AERP shortening. CONCLUSION: Short-term simulated OSA is associated with a progressive, but transient, AERP shortening and a PKC(Ɛ) translocation to LA membrane. Pharmacological I(K,ACh) and muscarinic receptor inhibition prevented transient INAP-induced AERP shortening, suggesting an involvement of I(K,ACh) in the transient arrhythmogenic AF substrate in OSA

    Place de la laparoscopie dans le traitement du cancer de l'endomètre [Laparoscopy in the management of endometrial cancer]

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    Les récents progrès de la laparoscopie ont modifié l'approche chirurgicale des patientes atteintes d'un cancer de l'endomètre. Le centre Swissendos Fribourg en collaboration avec l'AGO (Groupe de travail pour la gynécologie oncologique) et l'AGE (Groupe de travail pour la gynécologie endoscopique) ont entrepris d'élaborer un consensus basé sur l'évidence pour la pratique de la laparoscopie dans le traitement du cancer de l'endomètre. L'objectif a été de définir une approche propre à la Suisse en fournissant aux praticiens une aide à la prise en charge. Recent advance in laparoscopy have changed the surgical approach of endometrial cancer patients. The Swissendos Center, Fribourg, in collaboration with AGO (Groupe de travail pour la gynécologie oncologique) and AGE (groupe de travail pour la gynécologie endoscopique) have established a consensus based on the available evidence for the use of laparoscopy in the management of patients with endometrial cancer The main objective was to define Swiss clinical practice guidelines appropriate to the country and consistent with the needs of the physicians

    [Laparoscopy in the management of endometrial cancer]

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    Recent advance in laparoscopy have changed the surgical approach of endometrial cancer patients. The Swissendos Center, Fribourg, in collaboration with AGO (Groupe de travail pour la gynécologie oncologique) and AGE (groupe de travail pour la gynécologie endoscopique) have established a consensus based on the available evidence for the use of laparoscopy in the management of patients with endometrial cancer The main objective was to define Swiss clinical practice guidelines appropriate to the country and consistent with the needs of the physicians

    Basal cell carcinoma - molecular biology and potential new therapies.

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    Basal cell carcinoma (BCC) of the skin, the most common malignancy in individuals of mixed European descent, is increasing in incidence due to an aging population and sun exposure habits. The realization that aberrant activation of Hedgehog signaling is a pathognomonic feature of BCC development has opened the way for exciting progress toward understanding BCC biology and translation of this knowledge to the clinic. Genetic mouse models closely mimicking human BCCs have provided answers about the tumor cell of origin, and inhibition of Hedgehog signaling is emerging as a potentially useful targeted therapy for patients with advanced or multiple BCCs that have hitherto lacked effective treatment
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