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The first record of the Early Toarcian Oceanic Anoxic Event (c. 183 Ma) from the Southern Hemisphere is described from the Neuquen Basin, Argentina, identified chemostratigraphically on the basis of a relative increase in marine organic carbon and a characteristic negative carbon-isotope excursion (δ13Corg) in bulk rock and fossil wood. The negative excursion of -6 per mil in bulk organic carbon (falling to -31.3 per mil) crosses the boundary of the tenuicostatum-hoelderi Andean ammonite Zones, equivalent to the tenuicostatum-falciferum/serpentinum zones of Europe. These data indicate that the Early Toarcian Oceanic Anoxic Event was a global phenomenon.

Rocky tide pools are transition environments whose communities are affected by sudden temperature, salinity and nutrient fluctuations. Furthermore, these environments are exposed to multiple stressors and can be easily altered by human trampling. In particular, specific studies on rock pool heterobranchs communities are lacking for the Mediterranean Sea. In this study, the community of Heterobranchia (Mollusca: Gastropoda) living in an anthropized rock pools system in western Adriatic (Ancona, Italy) has been investigated and a first checklist of the sea slugs in this urbanized areas is provided. During the four months survey, a total of 452 specimens, belonging to 19 species and 12 families was recorded. Notable findings were the first record of Placida dendritica for the Conero Riviera, and the first records of Doto cervicenigra and Ercolania viridis for the western Adriatic Sea. Identification of trophic categories showed a diversified assemblage in terms of food sources mirroring a surprising species diversity. Moreover, we provide here the description of a peculiar behavior possibly used by sea slugs to cope with the stressful conditions within this semi-closed system.

BackgroundUndifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc) is a condition characterised by Raynaud’s phenomenon and either SSc marker autoantibodies or typical capillaroscopic findings or both, unsatisfying classification criteria for SSc1 and reported to evolve into definite SSc in about 50% of 60 cases over a 12–102 months follow-up time.2 We found marker autoantibody positivity to predict the evolution into SSc satisfying 2013 ACR criteria for the disease.3 ObjectivesTo investigate in patients followed-up for a longer time if distinct marker autoantibody specificities have a different predictive value.MethodsSixty-five patients consecutively admitted to a tertiary Rheumatology Unit from November 1 st 2000 to December 31 st 2016 and diagnosed as UCTD-risk-SSc were enrolled in the study. Patients were monitored for a median of 27 months (range 6–144) and were evaluated twice yearly to assess disease progression. Kaplan-Meier curves and the log-rank test were used to analyse differences in fulfilling the criteria for SSc between subsets. Risk prediction was assessed by univariate Cox regression analysis.ResultsDuring follow-up 40/53 marker autoantibody-positive patients (75.5%) versus 3/12 (25%) marker autoantibody negative ones satisfied SSc criteria (p=0.006). Out of them, 11/12 (91.7%) anti-topoisomerase (Scl70) positive versus 29/40 (72.5%) anti-centromere (ACA) positive patients evolved into definite SSc (p=0.04). In univariate analysis, anti-Scl70 positivity increased by 2-fold the risk of a definite SSc outcome (HR 2.1 95% CI 0.9–4.4) with respect to ACA positivity (HR 0.5 95% CI 0.2–1.0) (p=0.05). In addition 3/3 (100%) patients with avascular areas at baseline versus 40/62 (64.5%) with megacapillaries only or no capillaroscopic abnormalities satisfied SSc criteria over a 12–38 months follow-up time (p=0.06).ConclusionsWe confirm that autoantibody positivity patients presents a faster evolution. Moreover we first detected an increased HR of Scl-70 versus ACA positivity and a potential role of baseline detected avascular areas.References[1] Valentini G. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc). Autoimmun Rev2015.[2] Valentini G, et al. Early Systemic Sclerosis: Analysis of the Disease Course in Patients With Marker Autoantibody and/or Capillaroscopic Positivity. Arthritis Care Res2014.[3] van den Hoogen F, et al. 2013classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis2013.Disclosure of InterestNone declared

This paper presents different approaches to optimize wind turbine airfoils in an uncertain scenario. The approaches are specifically applied to the aerodynamic design optimization of a wind turbine airfoil accounting for the uncertainty in setting up the XFOIL's NCRIT constant: a parameter that is considered affected by a chain of aleatory and epistemic uncertainty. Subject to a set of aerodynamic and structural constraints, the uncertain response of the airfoil is optimized by means of both probability- and imprecise probability-based approaches. These solutions are compared with a reference airfoil optimized with a conventional design approach, in which the treatment of uncertainty is carried out in a simplistic fashion. Once evaluated in the probabilistic scenario, the airfoil designed with the conventional approach still achieves the largest aerodynamic efficiency mean. This airfoil is however affected by the largest performance sensitivity to NCRIT variations. The airfoils optimized by means of uncertainty-based approaches instead achieve larger performance robustness and reliability than the airfoil optimized with the conventional approach.

This study offers novel insights into the anatomy and predation strategy of a native invasive species in the Mediterranean Sea: the polychaete Hermodice carunculata, focusing on a population from Pantelleria (Sicily). By integrating direct underwater observations, optical and electron microscopy, and photographic material sourced online, we enhanced understanding of foregut anatomy, identified two feeding modalities, and suggested a relationship between the foregut structure and the species’ behavioural traits. The analysis confirmed that the worm’s pharynx is unarmed and revealed that the pharyngeal epithelium is adorned with bifurcated papillae whose function remains to be clarified. Considering that cnidarians are among the fireworm’s preferred prey, the papillae secretions may play a role in neutralizing nematocyst toxins. During field surveys, the fireworms were detected while feeding on a small assemblage of colonies of Eunicella singularis transplanted during an earlier restoration initiative. Hermodice carunculata could ingest up to 10 cm of a gorgonian branch, corresponding to 20–30 segments of the worm’s body, suggesting that Hermodice carunculata predation may pose a threat for restoration of temperate gorgonian forests. To conclude, this analysis provided valuable insights into the effective feeding strategy of the polychaete, which may inform targeted management approaches for controlling this invasive species.

Physiologically based pharmacokinetic (PBPK) models provide a framework useful for generating credible human pharmacokinetic predictions from data available at the earliest, preclinical stages of pharmaceutical research. With this approach, the pharmacokinetic implications of in vitro data are contextualized via scaling according to independent physiological information. However, in many cases these models also require model-based estimation of additional empirical scaling factors (SFs) in order to accurately recapitulate known human pharmacokinetic behavior. While this practice clearly improves data characterization, the introduction of empirically derived SFs may belie the extrapolative power commonly attributed to PBPK. This is particularly true when such SFs are compound dependent and/or when there are issues with regard to identifiability. As such, when empirically-derived SFs are necessary, a critical evaluation of parameter estimation and model structure are prudent. In this study, we applied a global optimization method to support model-based estimation of a single set of empirical SFs from intravenous clinical data on seven OATP substrates within the context of a previously published PBPK model as well as a revised PBPK model. The revised model with experimentally measured unbound fraction in liver, permeability between liver compartments, and permeability limited distribution to selected tissues improved data characterization. We utilized large-sample approximation and resampling approaches to estimate confidence intervals for the revised model in support of forward predictions that reflect the derived uncertainty. This work illustrates an objective approach to estimating empirically-derived SFs, systematically refining PBPK model performance and conveying the associated confidence in subsequent forward predictions.

By offering fast and flexible solutions to create 3D models, handheld scanners are currently under the focus of many research activities in various 3D data processing fields. The real-time constraint is still challenging to achieve especially when it comes with concurrent needs, such as level of accuracy in the data acquisition, easiness of recovering from scanning interruptions or loop closure abilities... Among them, object/scene tracking quality is one of the most critical. In this work, we describe two issues that affects its performance, focusing on the robustness of the process. Specifically, we encounter such issues at to two different steps while moving through the working pipeline of a prototype handheld scanner, i.e. (1) the data pre-processing before running a pairwise alignment between a frame and the model representation, called key-frame, and (2) the temporal and quality criteria that govern key-frame updates. Our approach simply consists in substituting the use of a rigid (uniform) pattern for sampling, with a random distribution of points. We then implement an adaptive statistical method to select suitable timing steps for key-frames refreshing, comparing this solution with a previous static one based on regular updating rate. We run experiments on a dataset created with our own scanner and we show that the adoption of such alternatives reduce the number of tracking failures, consequently increasing the robustness of the system, improving the quality of the alignments and preserving the real-time behavior of the device.

BackgroundCardiovascular disease (CVD) has emerged as one of the most important causes of mortality in systemic lupus erythematosus (SLE)1. In previous studies, disease activity, as assessed by SLEDAI (at the first visit or as mean annual value registered during follow-up), did not result to have any predictive role on the subsequent occurrence of CVD2–3.ObjectivesTo investigate the relationship between prolonged remission and the occurrence of a subsequent first CV event in patients with SLE.MethodsOut of 452 patients consecutively admitted to two tertiary Italian centres from November 1st 2000 to December 31st 2016, the 409 patients, who, at admission, had not experienced any CV event, had not received any anticoagulation therapy and had been visited at least biannually during follow-up, were considered for the present study. Prolonged remission was defined as a 5 year consecutive period of no disease activity based on SLEDAI-2K3.. Patients with prolonged remission were furtherly subdivided according to Zen et al4 into 3 groups: complete remission, clinical off-corticosteroids remission (offCR), clinical on-corticosteroids remission (onCR). Kaplan-Meier curves and the log-rank test were used to analyse differences in event-free survival between groups. Cox regression analysis was used to investigate disease and therapeutic features associated with the development of a first CV event.ResultsDuring 72 months median follow-up time, 29 (7.0%) CV events occurred (two events in patients who had undergone prolonged remission). Out of the 409 patients, 28 patients (6.8%) achieved a prolonged complete remission, 13 (3.1%) prolonged clinical offCR and 64 (15.5%) prolonged clinical onCR. Kaplan-Meier analysis revealed a greater overall CV event-free rate in patients achieving a prolonged remission compared to those in remission but for less than 5 years and patients not in remission (logrank test χ2=19.82; p=0.0001; figure 1). However, at Kaplan-Meier analysis, CV outcome was similar among patients in prolonged remission, irrespective of the type of remission achieved (p>0.05). At multivariate analysis, treatment with hydroxychloroquine for more than 5 years and prolonged remission were protective (HR 0.38; 95% CI 0.16–0.90; HR 0.08, 95% CI 0.01–0.53) while antiphospholipid syndrome increased the risk of a first CV event (HR 3.80; 95% CI 1.68–8.61). No differences were found between patients treated or not with aspirin. Nevertheless, among patients from Rome cohort, aspirin was only prescribed to patients with high traditional CV risk score.ConclusionsA prolonged remission, whichever the subtype, is associated with a better CV outcome and should be considered as a treat-to-target goal in the CV risk management of the lupus patient.References[1] Cervera R, et al. Medicine (Baltimore)2003.[2] Iudici M, et al. Rheumatology (Oxford)2016.[3] Fasano S, et al. Lupus2017.[4] Zen M, et al. Ann Rheum Dis2017.Disclosure of InterestNone declared

Purpose Preclinical data indicate there is strong synergism of action against Ewing sarcoma in sequential treatment with trabectedin followed by irinotecan and it appears to be related to a selective blockade of the transcription factor EWS–FLI1. This combination was evaluated in Ewing sarcoma patient who was progressing with standard therapies. Methods Trabectedin was given as a 24-h iv infusion on day 1 at the dose of 1 mg/sqm, and irinotecan 75 mg/sqm on day 2 and then on days 2 and 4, every 3 weeks from the seventh course. Results The therapy was well tolerated with transient hematological toxicity and transaminitis and induced stabilization of the disease lasting for 11 courses, with clinical improvement and marked reduction of the need for opioids. However, shortly before the 12th course, sudden death occurred, possibly due to cerebral stroke, presumably not related to the drug treatment. Conclusions The encouraging clinical benefit observed with the combination and its good tolerability deserves further investigation in Ewing sarcoma.

BackgroundPatients with UCTD (1) have been reported to present lung involvement most frequently characterized by nonspecific interstitial pneumonia (NSIP) at High Resolution Computerized Assial Tomography (HR-CAT), FVC and DLCO values lower than predicted (2).ObjectivesTo investigate UCTD patients for the presence of lung involvement and search for demographic, serological, capillaroscopic and organ involvement features associated with it.MethodsEighty-six patients consecutively admitted to the Rheumatology Unit of the Second University of Naples and satisfying criteria for the classification of UCTD (1) were enrolled into the study. Patients presenting with any major CTD marker autoantibody other than anti-Ro (SSA) and/or scleroderma capillaroscopic specific pattern were excluded. Each patient underwent a careful history, a complete physical examination, evaluation of serum Antinuclear (ANA) and anti Extraible Nuclear Antigens antibody (anti-ENA), videocapillaroscopy, echo-Doppler-cardiography with evaluation of Left ventricular E/A ratio. Those who consented also underwent HR-CAT and esophagotonometry. Interstitial lung disease (ILD) was defined by HR-CAT or, if unavailable, by FVC<80% plus DLCO<80%.ResultsThe table lists the features detected in the patients subdivided according to the presence of lung involvement. DLCO <80% was found in 30/86 (34.8%) patients; FVC <80% in 3/86 (1.2%); HR-CAT was carried in 36/86 (41.8%) patients. It pointed a lung involvement NSIP pattern in 5/36 patients (13%).An isolated reduction of DLCO resulted the be the most frequent finding and might depend on pulmonary vascular disease. Anti-SSA positivity and Capillaroscopic alterations were detected more frequently in patients with lung involvement (either isolated reduction of DLCO or ILD).ConclusionsWe detected a prevalence of ILD in UCTD lower than previously reported (2) (80%). Nevertheless, we found an isolated reduction of DLCO in about 35% of the UCTD patients. Lung involvement resulted to be significantly associated with capillaroscopic alterations and anti-SSA positivity.ReferencesMosca M, Tani C, Vagnani S, Carli L, Bombardieri S.The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun. 2014;48–49:50–2Kinder BW, Collard HR, Koth L, Daikh DI, Wolters PJ, Elicker B, Jones KD, King TE Jr. Am J Respir Crit Care Med. Oct 1;176(7):691–7Disclosure of InterestNone declared