Advancec characterization of multicaloric materials in pulsed magnetic fields.

The multicaloric effect is described by a temperature or entropy change of a material triggered by external stimuli applied or removed simultaneously or sequentially. The prerequisite for this is a material exhibiting multiple ferroic states. However, direct measurements of the effect are rarely reported. Now, for this reason, we built a measurement device allowing to determine the adiabatic temperature change in pulsed magnetic fields and, simultaneously, under the influence of a uniaxial load. We selected the all--metal Heusler alloy Ni-Mn-Ti-Co for our first test because of its enhanced mechanical properties and enormous magneto- and elastocaloric effects. Ni-Mn-Ti-Co was exposed to pulsed magnetic fields up to 10 T and uniaxial stresses up to 80 MPa, and the corresponding adiabatic temperature changes were measured. With our new experimental tool, we are able to better understand multicaloric materials and determine their cross-coupling responses to different stimuli

Structure of the mantle beneath the Alboran Basin from Magnetotelluric Soundings

We present results of marine MT acquisition in the Alboran sea that also incorporates previously acquired land MT from southern Spain into our analysis. The marine data show complex MT response functions with strong distortion due to seafloor topography and the coastline, but inclusion of high resolution topography and bathymetry and a seismically defined sediment unit into a 3‐D inversion model has allowed us to image the structure in the underlying mantle. The resulting resistivity model is broadly consistent with a geodynamic scenario that includes subduction of an eastward trending plate beneath Gibraltar, which plunges nearly vertically beneath the Alboran. Our model contains three primary features of interest: a resistive body beneath the central Alboran, which extends to a depth of ∼150 km. At this depth, the mantle resistivity decreases to values of ∼100 Ohm‐m, slightly higher than those seen in typical asthenosphere at the same depth. This transition suggests a change in slab properties with depth, perhaps reflecting a change in the nature of the seafloor subducted in the past. Two conductive features in our model suggest the presence of fluids released by the subducting slab or a small amount of partial melt in the upper mantle (or both). Of these, the one in the center of the Alboran basin, in the uppermost‐mantle (20-30 km depth) beneath Neogene volcanics and west of the termination of the Nekkor Fault, is consistent with geochemical models, which infer highly thinned lithosphere and shallow melting in order to explain the petrology of seafloor volcanics

Expediting DECam multimessenger counterpart searches with convolutional neural networks

Searches for counterparts to multimessenger events with optical imagers use difference imaging to detect new transient sources. However, even with existing artifact-detection algorithms, this process simultaneously returns several classes of false positives: false detections from poor-quality image subtractions, false detections from low signal-to-noise images, and detections of preexisting variable sources. Currently, human visual inspection to remove the false positives is a central part of multimessenger follow-up observations, but when next generation gravitational wave and neutrino detectors come online and increase the rate of multimessenger events, the visual inspection process will be prohibitively expensive. We approach this problem with two convolutional neural networks operating on the difference imaging outputs. The first network focuses on removing false detections and demonstrates an accuracy of 92% on our data set. The second network focuses on sorting all real detections by the probability of being a transient source within a host galaxy and distinguishes between various classes of images that previously required additional human inspection. We find the number of images requiring human inspection will decrease by a factor of 1.5 using our approach alone and a factor of 3.6 using our approach in combination with existing algorithms, facilitating rapid multimessenger counterpart identification by the astronomical communit

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

Single immune checkpoint blockade has shown limited activity in patients with neuroendocrine neoplasms (NENs). Here the authors report the results of a phase II clinical trial of durvalumab (anti-PD-L1) and tremelimumab (anti CTLA-4) in patients with advanced NENs of gastroenteropancreatic and lung origin. Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS

tumor infiltrating lymphocytes tils and pdl1 expression as prescreening enrichment biomarkers of clinical benefit to immune checkpoint inhibitors ci in early clinical trials ect

n/

Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1

BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's syndrome, plays a role in axon outgrowth and branching but also in epithelial morphogenesis. The molecular mechanism of its action is, however, widely unknown. Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a whey acidic protein (WAP) domain homologous to some serine protease inhibitors, and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1 (DmKal-1) has the same protein structure with minor differences, the most important of which is the presence of only two FnIII repeats and a C-terminal region showing a low similarity with the third and the fourth human FnIII repeats. We present a structure-function analysis of the different DmKal-1 domains, including a predicted heparan-sulfate binding site. RESULTS: This study was performed overexpressing wild type DmKal-1 and a series of deletion and point mutation proteins in two different tissues: the cephalopharyngeal skeleton of the embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal skeleton induced dosage-sensitive structural defects, and we used these phenotypes to perform a structure-function dissection of the protein domains. The reproduction of two deletions found in Kallmann's Syndrome patients determined a complete loss of function, whereas point mutations induced only minor alterations in the activity of the protein. Overexpression of the mutant proteins in the wing disc reveals that the functional relevance of the different DmKal-1 domains is dependent on the extracellular context. CONCLUSION: We suggest that the role played by the various protein domains differs in different extracellular contexts. This might explain why the same mutation analyzed in different tissues or in different cell culture lines often gives opposite phenotypes. These analyses also suggest that the FnIII repeats have a main and specific role, while the WAP domain might have only a modulator role, strictly connected to that of the fibronectins

ICO-ICS Praxis para el tratamiento médico y con irradiación de cáncer colorrectal

Tractament mèdic; Tractament amb irradiació; Còlon; Recte; CàncerMedical treatment; Irradiation treatment; Colon; Rectum; CancerTratamiento médico; Tratamiento con irradiación; Colon; Recto; CáncerEl càncer de còlon i recte (CCR) és el més freqüent a Catalunya segons dades del Pla director d’oncologia estimades per a 2017. La incidència del CCR és superior en homes, amb un increment anual de l'1,3% en els homes i el 0,5% en les dones des de 1994. A Espanya, segons l’informe de la SEOM, que recull dades de la REDECAN, posiciona el CCR com un dels més freqüents i probables de diagnosticar el 2019, amb 44.937 nous casos. Segons les dades dels registres de GLOBOCAN 2018, el CCR és el segon càncer amb més incidència a Europa. La incidència distribuïda per sexes és del 16,7% en homes i del 13,3% en dones. Els objectius d'aquesta guia són: -Desenvolupar, difondre, implementar i avaluar resultats de la ICO-ICSPraxi de càncer colorectal. -Disminuir la variabilitat terapèutica entre els pacients tractats als diferents centres d'aquesta institució. -Implementar els resultats de la terapèutica en els pacients amb adenocarcinoma de pàncrees tractats d'acord amb les recomanacions d'aquesta guia

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival