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

Increased use of cross-sectional imaging for follow-up does not improve post-recurrence survival of surgically treated initially localized R.C.C.: results from a European multicenter database (R.E.C.U.R.).

Objective: Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria's (per-protocol) or stated by the investigator. Materials and methods: Consecutive non-metastatic R.C.C. patients (n = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Results: Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time (p < 0.001). However, neither the image modality for detection nor ≥ 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. Conclusions: As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up

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

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

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments

Role of biomarkers in early infectious complications after lung transplantation

Background Infections and primary graft dysfunction are devastating complications in the immediate postoperative period following lung transplantation. Nowadays, reliable diagnostic tools are not available. Biomarkers could improve early infection diagnosis. Methods Multicentre prospective observational study that included all centres authorized to perform lung transplantation in Spain. Lung infection and/or primary graft dysfunction presentation during study period (first postoperative week) was determined. Biomarkers were measured on ICU admission and daily till ICU discharge or for the following 6 consecutive postoperative days. Results We included 233 patients. Median PCT levels were significantly lower in patients with no infection than in patients with Infection on all follow up days. PCT levels were similar for PGD grades 1 and 2 and increased significantly in grade 3. CRP levels were similar in all groups, and no significant differences were observed at any study time point. In the absence of PGD grade 3, PCT levels above median (0.50 ng/ml on admission or 1.17 ng/ml on day 1) were significantly associated with more than two- and three-fold increase in the risk of infection (adjusted Odds Ratio 2.37, 95% confidence interval 1.06 to 5.30 and 3.44, 95% confidence interval 1.52 to 7.78, respectively). Conclusions In the absence of severe primary graft dysfunction, procalcitonin can be useful in detecting infections during the first postoperative week. PGD grade 3 significantly increases PCT levels and interferes with the capacity of PCT as a marker of infection. PCT was superior to CRP in the diagnosis of infection during the study period

The interior of Mars as seen by InSight (Invited)

InSight is the first planetary mission dedicated to exploring the whole interior of a planet using geophysical methods, specifically seismology and geodesy. To this end, we observed seismic waves of distant marsquakes and inverted for interior models using differential travel times of phases reflected at the surface (PP, SS...) or the core mantle-boundary (ScS), as well as those converted at crustal interfaces. Compared to previous orbital observations1-3, the seismic data added decisive new insights with consequences for the formation of Mars: The global average crustal thickness of 24-75 km is at the low end of pre-mission estimates5. Together with the the thick lithosphere of 450-600 km5, this requires an enrichment of heat-producing elements in the crust by a factor of 13-20, compared to the primitive mantle. The iron-rich liquid core is 1790-1870 km in radius6, which rules out the existence of an insulating bridgmanite-dominated lower mantle on Mars. The large, and therefore low-density core needs a high amount of light elements. Given the geochemical boundary conditions, Sulfur alone cannot explain the estimated density of ~6 g/cm3 and volatile elements, such as oxygen, carbon or hydrogen are needed in significant amounts. This observation is difficult to reconcile with classical models of late formation from the same material as Earth. We also give an overview of open questions after three years of InSight operation on the surface of Mars, such as the potential existence of an inner core or compositional layers above the CM