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This paper discusses four peculiar cases of foraminiferal occurrences in a limestone bed of the Pennsylvanian (Myachkovian, upper Moscovian) of the Cantabrian Zone (northern Spain), which raise questions as to their possible interpretation: (1) the true range of the genus Pseudostaffella; (2) the possible marked tendency towards a thickness increase shown by the wall of the genus Putrella; (3) the origin of the apparent deformations observed in part of the fusulines, especially in some Beedeina specimens, here interpreted as alterations probably due to a foraminiferal disease; and (4) the observations made on clusters of recently found fused foraminifera, which invalidate one of the hypotheses so far provided to explain these aggregations while opening perspectives towards new interpretations. A new species, Putrella crassa Villa & Ueno, is introduced.

No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM.In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT,5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy).From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9-7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported.FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.

Objective: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. Methods: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. Results: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. Conclusions: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

La investigación sobre el contenido en foraminíferos del Carbonífero de la Cordillera Cantábrica ha proporciona­do diversas secciones de ejemplares que muestran el arrollamiento propio de los Biseriamminidae. Las caracterís­ticas peculiares de su pared nos inducen a considerarlos como representantes de un nuevo género para el que se propone el nombre de Tenebrosella.

En este trabajo se estudia el contenido en foraminíferos de la Formación Valdeteja en la Sección de la Sierra del Sueve, corte situado en la parte norte de la Cuenca Carbonífera Central. Los hallazgos de fusulináceos realizados en varios niveles de la formación muestran que en la mayor parte de la misma aparecen formas primitivas pertenecientes al Bashkiriense Inferior y que únicamente en los metros finales podría estar representado el Bashkiriense Superior. Estos datos paleontológicos revelan, por un lado, un depósito muy potente de sedimentos carbonatados durante el Bashkiriense Inferior y, por otro, suponen una valiosa información sobre la edad de unos tramos del Carbonífero en los que los diacronismos son muy acusados y los hallazgos paleontológicos no muy abundantes.

Ciertos grupos de caparazones de fusulininos que fueron considerados en el pasado como conchas aglutinantes, se interpretan en la actualidad como probables quistes reproductivos de tipo sicigial. Estos quistes aparecen con frecuencia en las microfacies calcáreas del Carbonífero de la Zona Cantábrica.

En las regiones del Ponga y Picos de Europa aflora una potente sucesión, esencialmente marina, de materiales carboníferos, cuya edad está comprendida entre el Turnesiense y, al menos, el Kasimoviense, y que en varios intervalos presenta una notable riqueza faunística. Los datos proporcionados por el estudio de distintos grupos de fósiles, esencialmente conodontos, foraminíferos, braquiópodos y ostrácodos muestran la existencia de notables diferencias en la composición general de las faunas tanto en sentido vertical como horizontal. En los niveles inferiores la fauna bentónica es escasa. Los conodontos, abundantes en los tramos más bajos (Turnesiense a Serpukhoviense), están representados por especies de amplia distribución geográfica, que permiten datar con precisión estos niveles en términos de la escala estratigráfica de Europa Occidental. A partir del Bashkiriense se instalan en la región comunidades bentónicas mucho más variadas. Las fusulinas permiten una estrecha correlación con los pisos y horizontes del Carbonífero Medio y Superior de Rusia. Especialmente llamativa es la asociación Bashkiriense de la Formación Ricacabiello, propia de la región del Ponga y áreas adyacentes. En el Moscoviense parece haberse dado el máximo desarrollo de una plataforma carbonatada somera, abierta y bien oxigenada, que sirvió de soporte a comunidades bentónicas ricas y variadas.

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it “as much as possible”, maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start. Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.gov #NCT02803086) aimed at developing predictive models of radiation-induced toxicities. Self-reported UI and personality traits, evaluated by means of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) and Eysenck Personality Questionnaire - Revised (EPQ-R) questionnaires, were assessed at ART/SRT start. Several endpoints based on baseline ICIQ-SF were investigated: frequency and amount of urine loss (ICIQ3 and ICIQ4, respectively), “objective” UI (ICIQ3 + 4), “subjective” UI (ICIQ5), and “TOTAL” UI (ICIQ3 +4 + 5). The relationship between each endpoint and time from prostatectomy to radiotherapy (TTRT) was investigated. The association between clinical and personality variables and each endpoint was tested by uni- and multivariable logistic regression. Results: TTRT was the strongest predictor for all endpoints (p-values ≤ 0.001), all scores improved between 4 and 8 months after prostatectomy, without any additional long-term recovery. Neuroticism independently predicted subjective UI, TOTAL UI, and daily frequency. Conclusions: Early UI recovery mostly depends on TTRT with no further improvement after 8 months from prostatectomy. Higher levels of neuroticism may overestimate UI.

The Campo de Caso section (eastern part of the Cantabrian Zone, NW Spain) exposes a middle to upper Moscovian (Middle Pennsylvanian) succession, up to 3500-m thick, consisting of marine shelfal and deltaic siliciclastic and shale deposits with numerous intercalated fossiliferous limestones. A limestone outcropping in the upper part of this section, close to the village of Tanes, has yielded a fusuline assemblage composed of species of the genera Eostaffella, Pseudonovella, Ozawainella, Pseudostaffella, Neostaffella, Schubertella, Fusiella, Taitzehoella, Fusulinella, Beedeina and Putrella . The specific composition of these genera, considered as a whole, indicates an early to mid- Myachkovian age; however, some of the taxa exhibit rare aspects, among which are the occurrence of pseudostaffellids having a “primitive” appearance recalling that of the Bashkirian Pseudostaffella , and a Putrella species exhibiting a wall that, at first glance, resembles the schwagerinid wall. Data gathered during this study question the validity of the genus Quasistaffella Solovieva 1986 and point to consider it as a junior synonymous of Pseudostaffella Thompson 1942.

Background and purpose: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. Materials and methods: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (ΔIBDQ). The 25th percentile values of these score variations were set as endpoints. DVHs of bowel loops for patients with/without toxicity were compared for each endpoint, having excluded patients with baseline scores

Tang, Mimi/0000-0002-3839-5293; Romano, Antonino/0000-0001-9742-9898; Zuberbier, Torsten/0000-0002-1466-8875; Thong, Bernard/0000-0002-6338-8482; EBO, Didier/0000-0003-0672-7529; Scala, Enrico/0000-0002-9391-9168; Monge Ortega, Olga Patricia/0000-0002-6195-417X WOS:000523267300003 PubMed: 32128023 Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen. WAO Board of Directors The authors wish to thank the allergy societies from the membership of the World Allergy Organization who provided critical review of the draft and the WAO Board of Directors for supporting this work.

The Hoyo Oscuro section (Andara Massif, southeastern part of Picos de Europa) is a comparatively small exposure of Pennsylvanian syntectonic deposits that shown angular unconformity on the fairly extensive pre-tectonic carbonate platform strata of Pennsylvanian age accumulated in the distalmost realms of the Variscan foreland basin of the Cantabrian Zone. Fusuline-bearing strata from this section yielded species belonging to the genera P seudostaffella, Ozawainella, Fusulinella, Protriticites, Pseudotriticites, Fusulina and Quasifusulinoides ; one of these forms, Protriticites schulzei Villa, is described as a new species from the Cantabrian Mountains. Fusuline assemblages allow us to correlate the Hoyo Oscuro strata with the syntectonic successions of the northern part of Picos de Europa (Gamonedo area) and with specific intervals of the Picos de Europa Formation that, according to currently accepted models, were pre-tectonic. The age data obtained for the oldest syntectonic deposits of the studied section are of key importance, since they constitute a new anchor point confirming the onset of the Variscan Orogeny in this part of the Cantabrian Zone.

The publisher regrets we have been made aware of the below errors: 1) In Table 15, row NOVEOS chemiluminescent assay is written “utilizes 40 μL (0.04 ml) of sample per result”. The correct value would be “4 μL (0.004 ml)" of sample per result.2) In Table 16, is written “NOVEOS menu has 79 available allergens, consisting of 69 extracts and 10 molecular allergens”. It should say “NOVEOS menu continues to increase and it has 152 total allergens with 108 extracts and 44 components".3) In Table 15, row “Euroimmun”, column “Patient's serum”, is written “1000 ml”. The correct value would be “0.1 ml (-0.4 ml)”.The publisher would like to apologise for any inconvenience caused.

The Valdorria carbonate platform, in northern Spain, features a well-preserved and continuous outcrop of a Bashkirian platform to basin transect. During the Asatauian (late Bashkirian), the platform growth changed gradually from a progradational to an aggradational mode, recording 10 most likely short-eccentricity-controlled cyclothems. The facies of the platform-top and slope have been mapped, and the architecture of each cyclothem schematically reconstructed. The distribution of microbial carbonates (microbially mediated precipitates), skeletal (grazers/burrowers, corals/filter feeders, algae, foraminifera, Osagia-like oncoids and Thartarella-Terebella worm tubes) and non-skeletal grains (faecal pellets) has been quantified for the transgressive–regressive periods of deposition (transgressive, maximum flooding, early and late regressive intervals) of each cyclothem. This study shows that the distribution of microbial carbonates, skeletal and non-skeletal grains along a carbonate platform transect is variable through time and mainly governed by a set of measurable interconnected factors regulating the local palaeoenvironments: the water depth and the wave energy (facies) along the platform profile (inner, outer, break, slope) during periods of sea-level fluctuations (transgressive to regressive intervals of deposition). Auloporid corals, siliceous sponges, phylloid algae and Osagia-like oncoids are characteristic of a low-energy environment situated from estimated palaeo-water depths of 25 to 80 metres below sea level (mbsl onward) that formed in the outer platform during the maximum-flooding intervals. Anthracoporella–Archaeolithoporella boundstone is characteristic of the moderate-energy environments created in the horizontal inner-platform during the transgressive intervals. Microbially mediated precipitates are reliable indicators of the slope and Masloviporidium(?) indicator of low-energy environments of the upper slope. On the platform-top, Ungdarella and Donezella are more abundant during the early regressive intervals than during any other interval. Stacheoids are mainly present in the water depth range of 10 to 60 mbsl, tournayellids from 15 to 35 mbsl and archaediscids from 15 to 75 mbsl, all in low- to moderate-energy conditions. Rugose corals are common in the water depth range of 5 to 35 mbsl, either during the transition from the early to the late regressive intervals, as solitary forms or forming boundstone, or during periods of higher sea-level stand, as solitary forms in floatstone. Fenestellids, fistuliporids and trilobites occur mainly in the slope, but are also common in the platform top during the maximum flooding and/or the early regressive intervals. Archaeolithoporella is a reliable indicator of the platform top deposits, but its abundance is closely linked to the presence of adequate substrates. A high abundance in the assemblage of gastropods, endothyrids, palaeotextulariids, bradyinids and fusulinids characterizes the platform top shallow-water coated-grain grainstones formed under high-energy currents during the late regressive intervals. Tetrataxids act as encrusters on microbial precipitates of the slope or on phylloid algae and Archaeolithoporella of the platform top, but are also observed as nuclei of coated grains. Brachiopods are more abundant in low- to moderate-energy and 35 to 55 mbsl environments that prevailed during the transgressive intervals. Faecal pellets were commonly observed in low-energy environments, from 50 to 325 mbsl, at the platform break and in the slope, and the same applies for Thartarella-Terebella worm tubes that are virtually absent in high-energy deposits. Finally, crinoids, lasiodiscids and tuberitinids are randomly distributed and are not indicative of any specific environment. The here well-constrained distribution patterns of microbial carbonates, skeletal and non-skeletal grains in Valdorria outcrop hold the potential to serve as a reference for interpretation of depositional environments of other platforms using biota associations and depositional texture, particularly in regions where the platform geometry is not preserved or is not fully exposed.

The Moscovian stratoype is located at the Moscow Basin (western Russian Platform), where fusulines have traditionally been used to subdivide the stage and to trace its lower boundary. However, fusuline assemblages from the lower Moscovian and the underlying upper Bashkirian show differences in species composition throughout Eurasia and also worldwide that make it difficult to establish correlations with the Russian Platform. This paper describes the succession of fusuline faunas yielded by three Cantabrian Zone (NW Spain) sections exposing the Bashkirian/Moscovian transition. Los Tornos and La Camocha sections are particularly relevant for they contain a fusuline record that could fill, at least partially, a gap existing at the base of the Moscovian stage stratotype. Another section, the Santo Firme section, is of interest in that it contains a cinerite that provided a numerical age at a level within the Bashkirian/Moscovian transition. Forty-nine fusuline taxa belonging to the Profusulinella Zone are described from these three sections, including the new species Schubertella multiforme , Profusulinella martinezi , Aljutovella asturiensis , and Eowedekindellina solovievae . In spite of the differences mentioned, attempts are made to correlate the fusulines from the Cantabrian Zone with the fusuline biozones defined in relevant Carboniferous areas of Eastern Europe (Russian Platform, Urals, Donets Basin).

Multidisciplinary management of oligometastatic breast cancer with local therapy could improve disease control. The aim of our study is the assessment of safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) in selected subset of patients.Oligometastastic patients from breast cancer were treated with SBRT for 1-3 lung and liver lesions, in an observational study. Inclusion criteria were: age18 years, ECOG 0-2, diagnosis of breast cancer, no extrapulmonary and/or extrahepatic disease, other metastatic sites stable or responding after chemotherapy were allowed, no life threatening conditions, less than 5 lung and liver lesions (with maximum diameter5 cm), chemotherapy completed at least 3 weeks before treatment, written informed consent. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-point was local control (LC). Secondary end-points were toxicity, overall survival (OS) and progression-free survival (PFS).From April 2010 to June 2014, 33 patients for a total number of 43 lesions were irradiated. Median follow up was 24 months (range 3-59). Actuarial LC rates were 98% at 1 year and 90% at 2 and 3 years. Complete response, partial response and progressive disease were detected in 25 (53.2%), 16 (34%), and 6 (12.8%) lesions, respectively. Median OS was 48 months. Actuarial OS rates at 1 and 2 years were 93% and 66% respectively. Median PFS was 11 months, with a PFS rate at 1 and 2 years of 48% and 27%, respectively. At univariate analysis DFI12 months, hormonal receptor positivity, medical therapies after SBRT showed a significant impact on OS. Treatment was well tolerated, with no G3-4 toxicities.SBRT is a safe and feasible alternative treatment of liver and lung oligometastases from breast cancer, in selected patients not amenable to surgery, with good local control and survival rate.

A fusuline species of the genus Parawedekindellina Safonova has been found in the Fito Formation of the Carboniferous of the Cantabrian Zone (NW Spain). Representatives of this genus had only previously been recorded from the Arctic and the Ural palaeobiogeographic provinces, and therefore the new species from Spain in the first record of the genus from the Palaeotethyan province. This finding is interpreted as evidence of temporary connections between the Ural and the Palaeotethys provinces

Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@.PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies. Keywords: Diagnosis, Molecular allergy, Cross reactivity, Panallergen, Specific IgE, PAMD@

Bone metastases occur in more than 80% of men with metastatic prostate cancer. Affecting the structural integrity of the bone, they can lead to skeletal complications and pain, with a negative impact on patient quality of life and survival. The last decade has witnessed tremendous advances in the treatment of metastatic PCa. New therapeutic options that prolong overall survival are now available. The optimization of bone metastasis management (and prevention of skeletal morbidities) is therefore of paramount importance to improve clinical outcome. Some issues are still debated, such as the most effective radiologic or nuclear medicine technique to diagnose and monitor bone disease, the ideal surrogate circulating marker to assess response or progression to treatment, patient selection, as well as the optimal sequencing or combination of available therapeutic options. Several healthcare professionals play a role in the treatment of metastatic PCa. The presence of a multidisciplinary team for the discussion of treatment strategies for each patient should be the standard of care.

Este artículo contiene 9 páginas, 6 figuras, 1 tabla., Marine protected areas (MPAs) are key tools to mitigate human impacts in coastal environments, promoting sustainable activities to conserve biodiversity. The designation of MPAs alone may not result in the lessening of some human threats, which is highly dependent on management goals and the related specific regulations that are adopted. Here, we develop and operationalize a local threat assessment framework. We develop indices to quantify the effectiveness of MPAs (or individual zones within MPAs in the case of multiple-use MPAs) in reducing anthropogenic extractive and non-extractive threats operating at local scale, focusing specifically on threats that can be managed through MPAs. We apply this framework in 15 Mediterranean MPAs to assess their threat reduction capacity. We show that fully protected areas effectively eliminate extractive activities, whereas the intensity of artisanal and recreational fishing within partially protected areas, paradoxically, is higher than that found outside MPAs, questioning their ability at reaching conservation targets. In addition, both fully and partially protected areas attract non-extractive activities that are potential threats. Overall, only three of the 15 MPAs had lower intensities for the entire set of eight threats considered, in respect to adjacent control unprotected areas. Understanding the intensity and occurrence of human threats operating at the local scale inside and around MPAs is important for assessing MPAs effectiveness in achieving the goals they have been designed for, informing management strategies, and prioritizing specific actions., This work was financially supported by the ERA-Net BiodivERsA (BUFFER project, 092337) and the EU-FP7 (COCONET project, 287844) and contributes to DG MARE SafeNet project, Ares(2017)2510058.

Extensive outcrops of fusuline-rich limestone strata of Pennsylvanian age occur in the Eastern or Andara Massif of the Picos de Europa mountains in Northern Spain. The stratigraphic section is composed of the upper part of the Picos de Europa Formation, a carbonate succession deposited on a broad platform top in a distal foreland-basin margin setting, and the unconformable overlying Las Llacerias Formation, which represents carbonate-ramp strata deposited during the deformation of the underlying Picos de Europa platform. The tectonic setting allowed the accumulation of a very thick stratigraphic succession during the late Pennsylvanian, when the basin was located at paleoequatorial latitudes in the gulf of the western Palaeo-Tethys Ocean, adjacent to the eastern coast of Pangea. An in-depth stratigraphic and micropaleontological study involving six sections and several isolated localities revealed an interval spanning the uppermost Moscovian to the lower-middle Kasimovian. This study has allowed us to establish a composite section, more than 400 m thick, recording the uppermost part of the Fusulinella Zone ( F. alvaradoi subzone), the Protriticites Zone and the Montiparus Zone. Forty-one fusuline taxa are described, including four new species, Protriticites grajalensis, P. quasiovoidalis, P. benshae, and Pseudotriticites cantabricus. The composition of the fusuline assemblages differs from those of the Carboniferous in key areas of Eastern Europe, and reveals their affinity to Central Asian assemblages as part of a separate biogeographic province. In spite of these paleobiogeographic differences, the observations on the fusuline evolutionary lineages, as well as the presence of a few common forms, made it possible to establish an approximate correlation between the Andara and the Eastern European successions. We also report a previously unknown thrust fault, refine the stratigraphy and age of the successions outcropping in the Andara Massif, and determine the diachronism of the base of the unconformable Las Llacerias Formation.

Seven centimetre-thick volcanic ash-fall layers interbedded within the thick Carboniferous successions of the Cantabrian Zone in northern Spain were dated by U–Pb zircon laser ablation inductively coupled plasma mass spectrometry across an interval ranging from Visean to Kasimovian, thus covering most of the Carboniferous period. All these ash layers occur in fossiliferous successions, allowing us to insert the radiometric data within a well-constrained biostratigraphic framework. Considering the analytical uncertainty, the obtained ages match the ages inferred from the conodont biostratigraphy established in the Mississippian succession (which hosts the oldest two ash layers, Visean in age), and the fusuline and mega- and microflora data from the strata hosting the Moscovian and Kasimovian (Westphalian–Stephanian) tonsteins. The age of a Langsettian tonstein along with data provided by several papers stating that in the Cantabrian Zone Langsettian floras were contemporaneous with lowermost Moscovian fusulines suggest that Langsettian floras could have been younger in Spain than in other areas. Our absolute ages provide new constraints not only for the correlation of the Carboniferous successions of the Cantabrian Zone with time-equivalent reference successions in other parts of the world but also for calibrating the Carboniferous global chronostratigraphic units based on marine fossils with the West European regional units., The authors acknowledge financial support from the Spanish Ministry of Economy and Competitiveness under projects CGL2013-46061-P, CGL2013-44458-P and CGL2016-76438-P (to J.F.-S.), project SV-PA-13-ECOEMP-45 and FEDER funding from the European Community.he authors acknowledge financial support from the Spanish Ministry of Economy and Competitiveness under projects CGL2013-46061-P, CGL2013-44458-P and CGL2016-76438-P (to J.F.-S.), project SV-PA-13-ECOEMP-45 and FEDER funding from the European Community.

The Pennsylvanian marine foreland basin of the Cantabrian Zone (NW Spain) is characterized by the unique development of kilometre-size and hundred-metre-thick carbonate platforms adjacent to deltaic systems. During Moscovian time, progradational clastic wedges fed by the orogen comprised proximal alluvial conglomerates and coal-bearing deltaic sequences to distal shelfal marine deposits associated with carbonate platforms (Escalada Fm.) and distal clay-rich submarine slopes. A first phase of carbonate platform development (Escalada I, upper Kashirian-lower Podolskian) reached a thickness of 400 m, nearly 50 km in width and developed a distal high-relief margin facing a starved basin, nearly 1000-m deep. Carbonate slope clinoforms dipped up to 30° and consisted of in situ microbial boundstone, pinching out downslope into calciturbidites, argillaceous spiculites and breccias. The second carbonate platform (Escalada II, upper Podolskian-lower Myachkovian) developed beyond the previous platform margin, following the basinward progradation of siliciclastic deposits. Both carbonate platforms include: (1) a lower part composed of siliciclastic-carbonate cyclothems characterized by coated-grain and ooid grainstones; and (2) a carbonate-dominated upper part, composed of tabular and mound-shaped wackestone and algal-microbial boundstone strata alternating at the decametre scale with skeletal and coated-grain grainstone beds. Carbonate platforms initiated in distal sectors of the foreland marine shelf during transgressions, when terrigenous sediments were stored in the proximal part, and developed further during highstands of 3rd-order sequences in a high-subsidence context. During the falling stage and lowstand systems tracts, deltaic systems prograded across the shelf burying the carbonate platforms. Key factors involved in the development of these unique carbonate platforms in an active foreland basin are: (1) the large size of the marine shelf (approaching 200 km in width); (2) the subsidence distribution pattern across the marine shelf, decreasing from proximal shoreline to distal sectors; (3) Pennsylvanian glacio-eustacy affecting carbonate lithofacies architecture; and (4) the environmental conditions optimal for fostering microbial and algal carbonate factories.

Cemented calcareous breccias appear in the Picos de Europa (Cantabrian Mountains, Spain) resting on glacially abraded surfaces and covered by moraines. U/Th dating of the calcite coating the clasts was successful in two samples, the oldest one indicating that the breccias accumulated during or prior to Marine Isotope Stage (MIS) 11, and the youngest indicating later cementation during MIS 8. The former introduces a limit for the age of the glaciation preceding the breccias, which cannot correspond to an event younger than MIS 12. This is the oldest absolute age so far obtained for intercalated glacial/interglacial deposits of the Iberian Peninsula.

Background To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. Methods Patients presenting early-stage breast cancer were enrolled in a phase II trial. Eligibility criteria: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T

Harmful algal blooms (HABs) are becoming more frequent as climate changes, with tropical species moving northward. Monitoring programs detecting the presence of toxic algae before they bloom are of paramount importance to protect aquatic ecosystems, aquaculture, human health and local economies. Rapid and reliable species identification methods using molecular barcodes coupled to biosensor detection tools have received increasing attention over the past decade as an alternative to the impractical standard microscopic counting-based techniques. This work reports on a PCR amplification-free electrochemical genosensor for the enhanced selective and sensitive detection of RNA from multiple Mediterranean toxic algal species. For a sandwich hybridization (SHA), we designed longer capture and signal probes for more specific target discrimination against a single base-pair mismatch from closely related species and for reproducible signals. We optimized experimental conditions, viz., minimal probe concentration in the SHA on a screen-printed gold electrode and selected the best electrochemical mediator. Probes from 13 Mediterranean dinoflagellate species were tested under optimized conditions and the format further tested for quantification of RNA from environmental samples. We not only enhanced the selectivity and sensitivity of the state-of-the-art toxic algal genosensors but also increased the repertoire of toxic algal biosensors in the Mediterranean, towards an integral and automatic monitoring system.

The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer.Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate-specific antigen (PSA) ≤ 20 ng/ml, Gleason Score7, International Prostate Symptom Score7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life.Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment.Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life.

Sedimentary cyclic sequences deposited during the Late Palaeozoic Ice Age are widespread. Glacio-eustatic control of the cyclic patterns is commonly accepted, and the durations of the cyclothems generally match the short- and long-eccentricity Milankovitch orbital parameters. Nevertheless, geochemical fingerprints of orbital parameters are poorly documented in deep-time sedimentary records. Here, we report on well-exposed Bashkirian cyclothems of c. 123 ka and c. 400 ka durations from the Valdorria platform. The shorter-term cyclothems can be grouped into longer-term composite sequences that are consistent with generally accepted durations of c. 125 ka and c. 400 ka for Milankovitch eccentricity cycles. The stratigraphic pattern is mirrored by the isotope geochemical signals, which show distinct recurring trends. These trends are confirmed by statistical tests. Whereas intrinsic factors and/or subaerial exposure related to sea-level lowstands might have truncated cycle patterns in tectonically stable basins, rapid subsidence of the Valdorria platform's foreland basin appears to have contributed to a faithful recording of cyclothems of different orders. The patterns and biostratigraphic constraint revealed in this study demonstrate the power of orbital forcing in imprinting sedimentary and geochemical signals in the rock record.

The 14 km wide Valdorria outcrop (Pennsylvanian, Northern Spain) is one of the few examples of entirely exposed flat-topped and high relief carbonate platforms reported in the fossil rock record. Laterally and vertically traceable stratal patterns expose three phases of growth. Phase I is a 430 m thick platform to slope succession that prograded over 6 km, and is dated as Early Bashkirian (Akavasian–Askynbashian). Phase II aggraded and prograded, exhibiting 180 m thickness of cyclical platform top deposits, dated as Late Bashkirian (Asatauian). Phase III is a mound-shape structure that developed over the platform top of Phase II as a new phase of platform nucleation. It is 535 m thick and 2 km wide, and dated as Late Bashkirian (Asatauian–Transition interval). The observed changes of growth styles during platform evolution, from a prograding to an aggrading–prograding system, and a rapid aggradational phase, are inferred to be controlled by flexural subsidence in the active Cantabrian foreland basin, at the Variscan orogenic front. The metre-scale shallowing-upward cycles of the platform top are most probably due to glacioeustasy, as evidenced by well-recorded subaerial exposure surfaces superimposed on subtidal deposits, and by a stratal pattern recurrent in a short interval of about 160 Kyr. Observations of outcropping Bashkirian cyclothems in an isolated carbonate system, devoid of siliciclastic input, are relevant for a better understanding of the impact of high-frequency sea-level fluctuations on the carbonate factory. Moreover, progradation of the platform margin during Phase I reaches a rate of 2500 m/Myr, and 1810 m/Myr during Phase II; rates that are high when compared to other Pennsylvanian examples. The aggradation rate of 447 m/Myr calculated for Late Bashkirian–Transition interval (Phases I and II; uncorrected for compaction, missing beats and erosion) is uncommonly high in comparison to coeval Pennsylvanian examples. The platform exhibits a self-nourishing prograding microbial boundstone-dominated slope. Thus, the slope shedding model applies well to Valdorria. However, Phase II recorded eustatic variations able to inhibit the slope microbial boundstone factory during low sea-level stands; this is marked by common slope red-stained breccias synchronous to platform top subaerial exposure phases. Contrarily, periods of relative high sea-level and rapid subsidence in Phase III registered a greater development of cemented microbial boundstone. These observed, partly opposing relationships of sea-level stands, shedding modes and slope architecture provide an improvement of the currently used slope shedding model. The overall architecture of the Valdorria outcrop compares well with that of other contemporaneous platforms, such as Sierra del Cuera and Bolshoi Karatau. Valdorria shares the high-relief and flat-topped, steep slopes, cyclothemic patterns and occurrence of karst features with the Pricaspian Basin platforms (Tengiz, Karachaganak and Kashagan), with minor variations in facies distribution of the internal platform. Furthermore, the continuous seismic-scale outcrop of Valdorria, together with its isolated setting and asymmetrical growth, makes it an additional good candidate for potential subsurface analogues of hydrocarbon-bearing systems.

Adrianus (Adriaan) Cornelis van Ginkel, a well-known specialist of fusulinid foraminifera, passed away on September 10, 2013, in Leiderdorp, Holland. Born in Wageningen on March 31, 1931, he was the son of Cornelis van Ginkel, the local veterinarian, and Margreta van Ginkel-Schouten. Throughout his primary and secondary school education in Wageningen, he showed a broad interest in any aspect of natural history. From 1950–1955 Adriaan studied geology at Leiden State University, where he received his undergraduate and M.Sc. degrees. His Master’s thesis dealt with the Carboniferous fusulinids and stratigraphy at the headwaters of the Pisuerga River, an area along the southern slope of the Cantabrian Mountains in northern Spain. That field work was his first contact with a region in which he developed close personal and professional ties that lasted for the rest of his life. After graduation Adriaan accepted employment as a micropaleontologist in the Turkish Geological Survey (MTA) in Ankara from 1957–1960, until returning to Leiden University to start his Ph.D. research supervised by Professor Aart Brouwer, head of the Department of Stratigraphy and Palaeontology. He focused on the Carboniferous fusulinids of northern Spain as part of a major project, led by Professor Lamoraal Ulbo de Sitter, on the stratigraphy, structure, and mapping of the southern slope of the Cantabrian Mountains. Based on this research Adriaan received his Ph.D. degree in May 1965 and later that year published an expanded version of his thesis entitled “Carboniferous fusulinids from the Cantabrian Mountains (Spain)” (van Ginkel, 1965) that included an extensive chapter on systematics. It was a pioneering work that offered a comprehensive study of the until-then poorly known fusulinids …