Radium-223 for patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases progressing on first-line abiraterone acetate or enzalutamide: A single-arm phase II trial

Bone metastases; Metastatic castration-resistant prostate cancerMetástasis óseas; Cáncer de próstata metastásico resistente a la castraciónMetàstasis òssies; Càncer de pròstata resistent a la castració metastàticPurpose The paper aims to evaluate the efficacy and safety of 223Ra in patients who progressed after first-line androgen deprivation therapy. Patients and methods EXCAAPE (NCT03002220) was a multicentre, single-arm, open-label, non-controlled phase IIa trial in 52 patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases who have progressed on abiraterone acetate or enzalutamide, up to six doses of 223Ra (55 kBq/kg of body weight per month). The primary end-point was radiographic progression-free survival (rPFS). Secondary end-points included rPFS based on androgen receptor splice variant 7 (AR-V7) expression in circulating tumour cells (CTCs), overall survival, and safety. Results Median rPFS was 5.5 months (95% CI 5.3–5.5). Median rPFS of patients with AR-V7(−) CTCs was longer than that of patients with AR-V7(+) CTCs (5.5 versus 2.2 months, respectively; P = 0.056). Median overall survival was 14.8 months (95% CI 11.2–not reached) and was significantly greater for AR-V7(−) patients than for AR-V7(+) patients (14.8 months versus 3.5 months, respectively; P < 0.01). 223Ra was well tolerated; anaemia and thrombocytopenia were the most common grade 3/4 adverse events (5.8% and 11.5%, respectively). Conclusions 223Ra seems to be a reasonable treatment for patients with metastatic castration-resistant prostate cancer and asymptomatic bone metastases progressing on novel hormonal therapy and had an acceptable safety profile.The study was conceived and designed by Joan Carles in collaboration with Medica Scientia Innovation Research (MEDSIR). MEDSIR, as legal sponsor of the study, is responsible for compliance with all clinical and regulatory procedures and adherence to the study protocol. MEDSIR had a role in study design, collection, management, analysis, and interpretation of the data and writing of the report. Bayer Inc. funded the study and provided 223Ra. The funder of the study had no role in data collection, management, data analysis, data interpretation, writing of the report, or decision to submit the manuscript for publication. All authors had full access to the data used to prepare the manuscript and participated in writing, editing, and/or critically reviewing the manuscript. The manuscript was written with editorial support from a medical writer, funded by MEDSIR. The corresponding author had final responsibility for the decision to submit for publication

Historic Landscapes of the Guadiamar River basin (Seville): Mining and metallurgy in the easternmost area of the Iberian Pyritic Belt

En este artículo se presentan los primeros resultados, incidiendo especialmente en los aspectos arqueometalúrgicos, del proyecto de investigación Los Paisajes del Guadiamar. Este proyecto se desarrolla desde el año 2010, f inanciado por la “Fundación Focus-Abengoa”, en el valle medio del río Guadiamar (centro-oeste de la provincia de Sevilla). Aunque aún no se ha con- cluido la obtención de todos los datos arqueológicos y analíticos, una valoración preliminar permite adelantar algunas conclusiones y, sobre todo, contrastar hipótesis y teorías enunciadas en anteriores trabajos de investigación.The f irst results of the research project Los Paisajes del Guadiamar are presented in this paper, paying special attention to archaeometallurgical aspects. This project has been going on since 2010, located in the mid-valley of the River Guadiamar (central-western area of the province of Seville) and backed by the “Fundación Focus-Abengoa”. Although not all the archaeo- logical and analytical data are yet available, a preliminary approach permits to put forward some conclusions and, above all, to validate or to refute hypotheses and theories proposed in previous research works

Biomechanical study of autograft anatomic reconstruction in lateral ankle instability

Introduction: The purpose of this work is perform a biomechanical comparison of anatomic reconstruction of the anterior talofibular ligament (ATFL) with the intact ATFL. Materials and methods: We studied 18 fresh cadaveric ankles with intact ATFL. Each specimen was clinically assessed with the anterior drawer (AD) and varus tilt (VT) tests and the angular movement in the three spatial planes (axial, coronal and sagittal) was measured with an arthrometer using a sensor located in the talus. Results: Statistically significant differences were found in the axial plane, between the intact ATFL versus the sectioned ATFL for AD test with p = 0.012, and for VT test with p = 0.013. Regarding the coronal plane, we also observed a statistically significant difference for VT test with p = 0.016. In the sagittal plane, there are no statistically significant differences in both maneuvers. No statistically significant differences were found when comparing the biomechanics of anatomic ligament reconstruction versus the intact ATFL. Conclusion: Autograft anatomic reconstruction of the ATFL showed biomechanical properties similar to those of the native ATFL, at the zero moment in a cadaveric model.publishersversionpublishe

Measurement of event shapes in deep inelastic scattering at HERA

Inclusive event-shape variables have been measured in the current region of the Breit frame for neutral current deep inelastic ep scattering using an integrated luminosity of 45.0 pb^-1 collected with the ZEUS detector at HERA. The variables studied included thrust, jet broadening and invariant jet mass. The kinematic range covered was 10 < Q^2 < 20,480 GeV^2 and 6.10^-4 < x < 0.6, where Q^2 is the virtuality of the exchanged boson and x is the Bjorken variable. The Q dependence of the shape variables has been used in conjunction with NLO perturbative calculations and the Dokshitzer-Webber non-perturbative corrections (`power corrections') to investigate the validity of this approach.Comment: 7+25 pages, 6 figure

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study

Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxyterminal telopeptide of type I collagen (b-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline b-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline b-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that b-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOLNovartis Oncology Spain for supporting this stud

Persistence of dissolved organic matter explained by molecular changes during its passage through soil

Dissolved organic matter affects fundamental biogeochemical processes in the soil such as nutrient cycling and organic matter storage. The current paradigm is that processing of dissolved organic matter converges to recalcitrant molecules (those that resist degradation) of low molecular mass and high molecular diversity through biotic and abiotic processes. Here we demonstrate that the molecular composition and properties of dissolved organic matter continuously change during soil passage and propose that this reflects a continual shifting of its sources. Using ultrahigh-resolution mass spectrometry and nuclear magnetic resonance spectroscopy, we studied the molecular changes of dissolved organic matter from the soil surface to 60 cm depth in 20 temperate grassland communities in soil type Eutric Fluvisol. Applying a semi-quantitative approach, we observed that plant-derived molecules were first broken down into molecules containing a large proportion of low-molecular-mass compounds. These low-molecular-mass compounds became less abundant during soil passage, whereas larger molecules, depleted in plant-related ligno-cellulosic structures, became more abundant. These findings indicate that the small plant-derived molecules were preferentially consumed by microorganisms and transformed into larger microbial-derived molecules. This suggests that dissolved organic matter is not intrinsically recalcitrant but instead persists in soil as a result of simultaneous consumption, transformation and formation

Measurement of the open-charm contribution to the diffractive proton structure function

Production of D*+/-(2010) mesons in diffractive deep inelastic scattering has been measured with the ZEUS detector at HERA using an integrated luminosity of 82 pb^{-1}. Diffractive events were identified by the presence of a large rapidity gap in the final state. Differential cross sections have been measured in the kinematic region 1.5 < Q^2 < 200 GeV^2, 0.02 < y < 0.7, x_{IP} < 0.035, beta 1.5 GeV and |\eta(D*+/-)| < 1.5. The measured cross sections are compared to theoretical predictions. The results are presented in terms of the open-charm contribution to the diffractive proton structure function. The data demonstrate a strong sensitivity to the diffractive parton densities.Comment: 35 pages, 11 figures, 6 table

Clinical Outcomes of a Zika Virus Mother-Child Pair Cohort in Spain

BACKGROUND: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. METHODS: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. RESULTS: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4-6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4-39.6%). CONCLUSIONS: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations

Photoproduction of D∗±D^{*\pm} mesons associated with a leading neutron

The photoproduction of $D^{*\pm} (2010)$ mesons associated with a leading neutron has been observed with the ZEUS detector in $ep$ collisions at HERA using an integrated luminosity of 80 pb$^{-1}$. The neutron carries a large fraction, {$x_L>0.2$}, of the incoming proton beam energy and is detected at very small production angles, {$\theta_n<0.8$ mrad}, an indication of peripheral scattering. The $D^*$ meson is centrally produced with pseudorapidity {$|\eta| 1.9$ GeV}, which is large compared to the average transverse momentum of the neutron of 0.22 GeV. The ratio of neutron-tagged to inclusive $D^*$ production is $8.85\pm 0.93({\rm stat.})^{+0.48}_{-0.61}({\rm syst.})\%$ in the photon-proton center-of-mass energy range {$130 <W<280$ GeV}. The data suggest that the presence of a hard scale enhances the fraction of events with a leading neutron in the final state.Comment: 28 pages, 4 figures, 2 table