640 research outputs found

    Surface waves and crustal structure on Mars

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    We detected surface waves from two meteorite impacts on Mars. By measuring group velocity dispersion along the impact-lander path, we obtained a direct constraint on crustal structure away from the InSight lander. The crust north of the equatorial dichotomy had a shear wave velocity of approximately 3.2 kilometers per second in the 5- to 30-kilometer depth range, with little depth variation. This implies a higher crustal density than inferred beneath the lander, suggesting either compositional differences or reduced porosity in the volcanic areas traversed by the surface waves. The lower velocities and the crustal layering observed beneath the landing site down to a 10-kilometer depth are not a global feature. Structural variations revealed by surface waves hold implications for models of the formation and thickness of the martian crust.D.K., S.C., D.G., J.C., C.D., A. K., S.C.S., N.D., and G.Z. were supported by the ETH+ funding scheme (ETH+02 19-1: ‚ÄúPlanet Mars‚ÄĚ). Marsquake Service operations at ETH Z√ľrich were supported by ETH Research grant ETH-06 17-02. N.C.S. and V.L. were supported by NASA PSP grant no. 80NSSC18K1628. Q.H. and E.B. are funded by NASA grant 80NSSC18K1680. C.B. and J.L. were supported by NASA InSight PSP grant no. 80NSSC18K1679. S.D.K. was supported by NASA InSight PSP grant no. 80NSSC18K1623. P.L., E.B., M.D., H.S., E.S., M.W., Z.X., T.W., M.P., R.F.G. were supported by CNES and the Agence Nationale de la Recherche (ANR-19-CE31-0008-08 MAGIS) for SEIS operation and SEIS Science analysis. A.H., C.C. and W.T.P. were supported by the UKSA under grant nos. ST/R002096/1, ST/ W002523/1 and ST/V00638X/1. Numerical computations of McMC Approach 2 were performed on the S-CAPAD/DANTE platform (IPGP, France) and using the HPC resources of IDRIS under the allocation A0110413017 made by GENCI. A.H. was supported by the UKSA under grant nos. ST/R002096/1 and ST/W002523/1. F.N. was supported by InSight PSP 80NSSC18K1627. I.J.D. was supported by NASA InSight PSP grant no. 80NSSC20K0971. L.V.P. was funded by NASANNN12AA01C with subcontract JPL-1515835. The research was carried out in part by W.B.B., M.G. and M.P.P. at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004)Peer reviewe

    Management of patients with advanced prostate cancer‚ÄĒmetastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

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    © 2023 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.ejca.2023.02.018Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.Published versio

    S1222a ‚Äď The Largest Marsquake Detected by InSight

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    NASA’s InSight has detected a large magnitude seismic event, labelled S1222a. The event has a moment magnitude of M(Ma)(W)4.7, with 5 times more seismic moment compared to the second largest even. The event is so large that features are clearly observed that were not seen in any previously detected events. In addition to body phases and Rayleigh waves, we also see Love waves, minor arc surface wave overtones, and multi-orbit surface waves. At long periods, the coda event exceeds 10 hours. The event locates close to the North-South dichotomy and outside the tectonically active Cerberus Fossae region. S1222a does not show any evident geological or tectonic features. The event is extremely rich in frequency content, extending from below 1/30 Hz up to 35 Hz. The event was classified as a broadband type event; we also observe coda decay and polarization similar to that of very high frequency type events.ISSN:0094-8276ISSN:1944-800

    Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

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    : The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p‚ÄČ=‚ÄČ0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p‚ÄČ=‚ÄČ0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p‚ÄČ=‚ÄČ0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p‚ÄČ=‚ÄČ0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p‚ÄČ=‚ÄČ0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p‚ÄČ=‚ÄČ0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p‚ÄČ=‚ÄČ0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p‚ÄČ<‚ÄČ0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p‚ÄČ=‚ÄČ0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p‚ÄČ=‚ÄČ0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

    Genomic‚Äďtranscriptomic evolution in lung cancer and metastasis

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    Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic‚Äďtranscriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary‚Äďmetastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

    Dise√Īo de pavimento y se√Īalizaci√≥n de v√≠as de la prolongaci√≥n avenida Grau del distrito veintis√©is de octubre, provincia de Piura, 2022

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    Este presente trabajo de investigaci√≥n se desarroll√≥ en la Prolongaci√≥n de la Avenida Grau en el Distrito de 26 de octubre ‚Äď Piura, la cual se consider√≥ para el estudio 4.98 km de la v√≠a, mediante una investigaci√≥n de tipo Aplicada. Con el objetivo principal de dise√Īar el Pavimento para mejorar la Transitabilidad y proponer un dise√Īo de se√Īalizaci√≥n vial en la zona. Se realizaron estudios de Tr√°fico durante 7 d√≠as de la semana en dos estaciones m√°s cr√≠ticas de la v√≠a, las cuales son E-01 Prolongaci√≥n Av. Grau con intersecci√≥n Av. Ra√ļl Mata la Cruz y E-02 Prolongaci√≥n Av. Grau con intersecci√≥n Av. C√©sar Vallejo, donde se aplic√≥ la metodolog√≠a de conteos y se cuantifico el volumen de tr√°fico para obtener el IMDA. Obtuvimos el permiso de la Municipalidad del Distrito 26 de octubre para realizar nuestro estudio de Suelos, la cual se efectuaron 05 calicatas a cielo abierto para poder obtener muestras, estas fueron llevadas al laboratorio para realizar los ensayos correspondientes, la cual obtuvimos un CBR para nuestra sub rasante de buena calidad, cabe precisar que se eligi√≥ el valor m√≠nimo de 14.00% para el dise√Īo. Teniendo estos resultados aplicamos el m√©todo de dise√Īo de AASTHO, Guide for Design of Pavement Structures 1993, acompa√Īado con el Manual de Carreteras y la Norma T√©cnica CE. 010 de Pavimentos Urbanos, se identificaron los espesores del pavimento flexible teniendo como resultado para la carpeta asf√°ltica un espesor de 7 cm, para la Base 30cm y para la Sub base 20 cm. Finalmente se incorpor√≥ un dise√Īo arquitect√≥nico y se√Īalizaci√≥n Vial, utilizando Manuales de dispositivos de Control de Transito Automotor para Calles y Carreteras, adecuado para nuestra v√≠a en estudio en donde hemos podido realizarla mediante unos softwares Revit y Twinmotion.This present research work was developed in the Extension of Grau Avenue in the District of 26 de Octubre - Piura, which was considered for the study 4.98 km of the road, through an Applied type investigation. With the main objective of designing the Pavement to improve trafficability and propose a design of road signs in the area. Traffic studies were carried out during 7 days of the week in two most critical stations of the road, which are E-01 extension Grau Avenue with intersection Ra√ļl Mata la Cruz Avenue and E-02 extension Grau Avenue with intersection C√©sar Vallejo Avenue where the counting methodology was applied and the volume of traffic was quantified to obtain my IMDa. We obtained permission from the Municipality of the District 26 de Octubre to carry out our soil study, which 05 test pits were carried out in the open to obtain samples, these were taken to the laboratory to carry out the corresponding tests, which we obtained a CBR for our good quality subgrade, it should be noted that the minimum value of 14.00% was chosen for the design. Having these results, we applied the AASTHO design method, Guide for Design of Pavement Structures 1993, accompanied by the Highway Manual and the CE Technical Standard. 010 of Urban Pavements, the thicknesses of the flexible pavement were identified, resulting in a thickness of 7 cm for the asphalt layer, 30 cm for the Base and 20 cm for the Sub-base. Finally, an architectural design and road signage was incorporated, using Manuals for Automotive Traffic Control devices for Streets and Highways, suitable for our road under study where we have been able to carry it out using Revit and Twinmotion software.Tesi

    Early VTE prophylaxis in severe traumatic brain injury: A propensity score weighted EAST multicenter study.

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    BACKGROUND: Patients with traumatic brain injury (TBI) are at high risk of venous thromboembolism events (VTE). We hypothesized that early chemical VTE prophylaxis initiation (‚ȧ24 hours of a stable head CT) in severe TBI would reduce VTE without increasing risk of intracranial hemorrhage expansion (ICHE). METHODS: A retrospective review of adult patients 18 years or older with isolated severe TBI (Abbreviated Injury Scale score, ‚Č• 3) who were admitted to 24 Level I and Level II trauma centers from January 1, 2014 to December 31 2020 was conducted. Patients were divided into those who did not receive any VTE prophylaxis (NO VTEP), who received VTE prophylaxis ‚ȧ24 hours after stable head CT (VTEP ‚ȧ24) and who received VTE prophylaxis \u3e24 hours after stable head CT (VTEP\u3e24). Primary outcomes were VTE and ICHE. Covariate balancing propensity score weighting was utilized to balance demographic and clinical characteristics across three groups. Weighted univariate logistic regression models were estimated for VTE and ICHE with patient group as predictor of interest. RESULTS: Of 3,936 patients, 1,784 met inclusion criteria. Incidences of VTE was significantly higher in the VTEP\u3e24 group, with higher incidences of DVT in the group. Higher incidences of ICHE were observed in the VTEP‚ȧ24 and VTEP\u3e24 groups. After propensity score weighting, there was a higher risk of VTE in patients in VTEP \u3e24 compared with those in VTEP‚ȧ24 (odds ratio, 1.51; 95% confidence interval, 0.69-3.30; p = 0.307), however was not significant. Although, the No VTEP group had decreased odds of having ICHE compared with VTEP‚ȧ24 (odds ratio, 0.75; 95% confidence interval, 0.55-1.02, p = 0.070), the result was not statistically significant. CONCLUSION: In this large multi-center analysis, there were no significant differences in VTE based on timing of initiation of VTE prophylaxis. Patients who never received VTE prophylaxis had decreased odds of ICHE. Further evaluation of VTE prophylaxis in larger randomized studies will be necessary for definitive conclusions. LEVEL OF EVIDENCE: Therapeutic Care Management; Level III

    Same-day testing with initiation of antiretroviral therapy or tuberculosis treatment versus standard care for persons presenting with tuberculosis symptoms at HIV diagnosis: A randomized open-label trial from Haiti.

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    BackgroundSame-day HIV testing and antiretroviral therapy (ART) initiation is being widely implemented. However, the optimal timing of ART among patients with tuberculosis (TB) symptoms is unknown. We hypothesized that same-day treatment (TB treatment for those diagnosed with TB; ART for those not diagnosed with TB) would be superior to standard care in this population.Methods and findingsWe conducted an open-label trial among adults with TB symptoms at initial HIV diagnosis at GHESKIO in Haiti; participants were recruited and randomized on the same day. Participants were randomized in a 1:1 ratio to same-day treatment (same-day TB testing with same-day TB treatment if TB diagnosed; same-day ART if TB not diagnosed) versus standard care (initiating TB treatment within 7 days and delaying ART to day 7 if TB not diagnosed). In both groups, ART was initiated 2 weeks after TB treatment. The primary outcome was retention in care with 48-week HIV-1 RNA ConclusionsIn patients with TB symptoms at HIV diagnosis, we found that same-day treatment was not associated with superior retention and viral suppression. In this study, a short delay in ART initiation did not appear to compromise outcomes.Trial registrationThis study is registered with ClinicalTrials.gov NCT03154320
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