Process for producing high strength alumina

A vacuum hot pressed alumina material having small, isometric grains; a uniform distribution thereof; relatively low, predominantly transgranular porosity; and a density approaching the theoretical density of pure alumina produced by vacuum hot pressing alumina powder which contains at least 98.0% alumina, is substantially free of any sintering aids or any other additives, and has a median particle size less than about 3 microns, in a vacuum hot press operated at a temperature of at least about 1350° C. and a pressure of at least 28 MPa (3500 PSI) for a sintering period of at least 1.5 hours. The vacuum hot pressed alumina material also has compressive strength, flexural strength, impact strength, and wear resistance superior to that for most conventional sintered alumina materials.https://digitalcommons.mtu.edu/patents/1072/thumbnail.jp

High strength alumina and process for producing same

A vacuum hot pressed alumina material having small, isometric grains; a uniform distribution thereof; relatively low, predominantly transgranular porosity; and a density approaching the theoretical density of pure alumina produced by vacuum hot pressing alumina powder which contains at least 98.0% alumina, is substantially free of any sintering aids or any other additives, and has a median particle size less than about 3 microns, in a vacuum hot press operated at a temperature of at least about 1350° C. and a pressure of at least 28 MPa (3500 PSI) for a sintering period of at least 1.5 hours. The vacuum hot pressed alumina material also has compressive strength, flexural strength, impact strength, and wear resistance superior to that for most conventional sintered alumina materials.https://digitalcommons.mtu.edu/patents/1075/thumbnail.jp

Polyethylene glycol-coated collagen patch (hemopatch®) in open partial nephrectomy

PURPOSE To describe the results of a polyethylene glycol-coated collagen patch, Hemopatch® on blood loss, surgical time and renal function in partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS Out of a single surgeon cohort of n = 565 patients undergoing conventional open PN (CPN) between 01/2015 and 12/2017 at the University of Munich a consecutive subgroup (n = 42) was operated on using a polyethylene glycol-coated collagen-based sealant Hemopatch® (Baxter International Inc., Deerfield, IL, USA) (HPN). RESULTS Median age was 65.2~years (range 12.7-95.2) with median follow-up of 9.43~months (0.03-49.15). Baseline renal function (CKD-EPI) was 78.56~ml/min/1.73~m2 (range 20.38-143.09) with a non-significant decline to 74.78~ml/min/1.73~m2 (range 3.75-167.74) at follow-up. In CPN 46% had low complexity, 33% moderate complexity and 20% high complexity lesions with 33% low, 40% moderate and 27% high complexity masses in HPN. Median tumor size was 4.3~cm (range 1-38~cm) in CPN with 4.8~cm (range 3.8-18.3~cm) with HPN, p = 0.293. Median blood loss and duration of surgery was significantly lower in the HPN group vs. CPN (146~ml ± 195 vs. 114~ml ± 159~ml; p = 0.021; 43~min ± 27 for HPN vs. 53~min ± 49; p = 0.035) with no difference in clamping time (12.6~min ± 8.6 for HPN vs. 12.0~min ± 9.5; p = 0.701). CONCLUSIONS Hemopatch® supported renoraphy shows promising results compared to standard renoraphy in PN. No side effects were seen. Further studies should evaluate the prevention of arterio-venous or urinary fistulas. In complex partial nephrectomies Hemopatch® supported renoraphy should be considered

Рекомендации по лечению пациентов с прогрессирующим или метастатическим почечно-клеточным раком комбинацией ленватиниба и эверолимуса

.На сегодняшний день существует несколько вариантов терапии 2-й линии для пациентов с почечно-клеточным раком после неудачи 1-й линии терапии ингибиторами тирозинкиназ. Недавно были одобрены для лечения кабозантиниб, ниволумаб и комбинация ленватиниб + эверолимус. Отсутствие надежных биомаркеров, а также ограниченность данных проспективных сравнений различных препаратов затрудняют выбор тактики лечения 2-й линии в рутинной клинической практике.В настоящем обзоре мы описываем профиль безопасности комбинации ленватиниб + эверолимус при почечно-клеточном раке. Данная комбинация обеспечила наиболее высокие показатели объективного ответа на терапию, выживаемости без прогрессирования и общей выживаемости в исследованиях с перекрестным дизайном. В то же время профиль безопасности этой комбинации, включая частоту общих и тяжелых нежелательных явлений, процент пациентов, которым потребовалось снижение дозы или полная отмена лечения, был менее благоприятным по сравнению с доступными вариантами монотерапии. Это позволяет предположить, что более тщательный контроль токсических реакций может способствовать достижению максимальной активности этих двух средств, одновременно защищая пациентов от неоправданного вреда.Цель — разработка междисциплинарных рекомендаций для пациентов и лиц, осуществляющих уход за ними, перед началом лечения комбинацией ленватиниб + эверолимус, в том числе по контролю терапии с точки зрения повседневной клинической практики.Основные положения:•             Комбинация ленватиниба и эверолимуса одобрена для лечения пациентов с почечно-клеточным раком, рефрактерным к терапии ингибиторами тирозинкиназ, на основании высоких показателей объективного ответа, длительной выживаемости без прогрессирования и общей выживаемости.•             Профиль безопасности этой комбинации включает высокую частоту общих и тяжелых нежелательных явлений, при этом многие пациенты нуждаются в снижении дозы или прекращении лечения. Это позволяет предположить, что более эффективный контроль токсических реакций может способствовать достижению максимальной активности комбинации препаратов, одновременно защищая пациентов от неоправданного вреда.•             В этой статье мы представили мультидисциплинарные рекомендации по консультированию пациентов и лиц, осуществляющих уход за ними, перед началом лечения ленватинибом в комбинации с эверолимусом, в том числе по контролю терапии с точки зрения повседневной клинической практики.Публикуется на русском языке с разрешения авторов. Оригинал: Grande E., Glen H., Aller J. et al. Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma. Expert Opinion on Drug Safety 2017. DOI: 10.1080/14740338.2017.1380624

Between platonic love and internet pornography

The article sets out to show how an holistic approach in matters of sexuality is always more helpful than one-sided approaches. On the issue of internet pornography, the authors suggest that the recent anti-masturbation online movement ‘no fapping’ is based on wrong conclusions from insufficient evidence. We suggest that a holistic approach is called for, with emphasis on the embodied human. Abstinence or what is understood by ‘Platonic love’ is not a solution, according to Plato himself. From a phenomenological perspective, we suggest owning up to our strange bodies and habitualising sexual activity

18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results

INTRODUCTION Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8~weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT

Two-dimensional finite element simulation of fracture and fatigue behaviours of alumina microstructures for hip prosthesis

This paper describes a two-dimensional (2D) finite element simulation for fracture and fatigue behaviours of pure alumina microstructures such as those found at hip prostheses. Finite element models are developed using actual Al2O3 microstructures and a bilinear cohesive zone law. Simulation conditions are similar to those found at a slip zone in a dry contact between a femoral head and an acetabular cup of hip prosthesis. Contact stresses are imposed to generate cracks in the models. Magnitudes of imposed stresses are higher than those found at the microscopic scale. Effects of microstructures and contact stresses are investigated in terms of crack formation. In addition, fatigue behaviour of the microstructure is determined by performing simulations under cyclic loading conditions. It is shown that crack density observed in a microstructure increases with increasing magnitude of applied contact stress. Moreover, crack density increases linearly with respect to the number of fatigue cycles within a given contact stress range. Meanwhile, as applied contact stress increases, number of cycles to failure decreases gradually. Finally, this proposed finite element simulation offers an effective method for identifying fracture and fatigue behaviours of a microstructure provided that microstructure images are available

68Ga-EMP-100 PET/CT-a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma-first in-human biodistribution and imaging results

BACKGROUND 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients

Pressure dependent relaxation in the photo-excited Mott insulator ETF2TCNQ:Influence of hopping and correlations on quasiparticle recombination rates

Femtosecond relaxation of photo-excited quasiparticles in the one dimensional Mott insulator ET-F2TCNQ are measured as a function of external pressure, which is used to tune the electronic structure. By fitting the static optical properties and measuring femtosecond decay times at each pressure value, we correlate the relaxation rates with the electronic bandwidth t and on the intersite correlation energy V. The scaling of relaxation times with microscopic parameters is different than for metals and semiconductors. The competition between localization and delocalization of the Mott-Hubbard exciton dictates the efficiency of the decay, as exposed by a fit based on the solution of the time-dependent extended Hubbard Hamiltonian.Comment: 24 pages, 7 figures, final version including supplementary material

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

Funding Information: Marius M. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, MSD, and Pfizer. Nicola Benjamin has received fees for lectures and/or consultations from Actelion. Ekkehard Grünig has received fees for lectures and/or consultations from Actelion, Bayer, GSK, MSD, United Therapeutics, and Pfizer. Karen M. Olsson has received fees for lectures and/or consultations from Actelion, Bayer, United Therapeutics, GSK, and Pfizer. C. Dario Vizza has received fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics Europe. Anton Vonk-Noordegraaf has received fees for lectures and/or consultation from Actelion, Bayer, GSK, and MSD. Oliver Distler has/had a consultancy relationship with and/or has received research funding from 4-D Science, Actelion, Active Biotec, Bayer, Biogen Idec, Boehringer Ingelheim Pharma, BMS, ChemoAb, EpiPharm, Ergonex, espeRare foundation, GSK, Genentech/Roche, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe, Pharmacyclics, Pfizer, Sanofi, Serodapharm, and Sinoxa in the area of potential treatments of scleroderma and its complications including pulmonary arterial hypertension. In addition, Prof Distler has a patent for mir-29 for the treatment of systemic sclerosis licensed. Christian Opitz has received fees from Actelion, Bayer, GSK, Pfizer, and Novartis. J. Simon R. Gibbs has received fees for lectures and/or consultations from Actelion, Bayer, Bellerophon, GSK, MSD, and Pfizer. Marion Delcroix has received fees from Actelion, Bayer, GSK, and MSD. H. Ardeschir Ghofrani has received fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer, and United Therapeutics. Doerte Huscher has received fees for lectures and consultations from Actelion. David Pittrow has received fees for consultations from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi. Stephan Rosenkranz has received fees for lectures and/or consultations from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics. Martin Claussen reports honoraria for lectures from Boehringer Ingelheim Pharma GmbH and Roche Pharma and for serving on advisory boards from Boehringer Ingelheim, outside the submitted work. Heinrike Wilkens reports personal fees from Boehringer and Roche during the conduct of the study and personal fees from Bayer, Biotest, Actelion, GSK, and Pfizer outside the submitted work. Juergen Behr received grants from Boehringer Ingelheim and personal fees for consultation or lectures from Actelion, Bayer, Boehringer Ingelheim, and Roche. Hubert Wirtz reports personal fees from Boehringer Ingelheim and Roche outside the submitted work. Hening Gall reports personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics outside the submitted work. Elena Pfeuffer-Jovic reports personal fees from Actelion, Boehringer Ingelheim, Novartis, and OMT outside the submitted work. Laura Scelsi reports personal fees from Actelion, Bayer, and MSD outside the submitted work. Siliva Ulrich reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, and grants and personal fees from Actelion SA/Johnson & Johnson Switzerland and MSD Switzerland outside the submitted work. The remaining authors have no conflicts of interest to disclose. Funding Information: This work was supported by the German Centre of Lung Research (DZL). COMPERA is funded by unrestricted grants from Acceleron , Actelion Pharmaceuticals , Bayer , OMT , and GSK . These companies were not involved in data analysis or the writing of this manuscript. Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.publishersversionPeer reviewe