The use of aerial- and close-range photogrammetry for the mapping of the Lavini di Marco tracksite (Hettangian, Southern Alps, NE Italy)

(EXCERPT FROM ABSTRACT) Close-range photogrammetry was executed following the procedure proposed by Mallison & Wings (2014). More than seventy 3D models were obtained and interpreted by means of color-coded and contour line images, which allow to improve the ichno- logical knowledge of the tracksite. The 3D models of the best-preserved tracks were used for the osteological reconstruction of the trackmakers’ autopodia, supposing the arthral position of the phalangeal pads. Three indirect methods were used to correlate tracks and their trackmakers: (i) synapomorphy-based approach; (ii) phenetic correlation; (iii) coincidence correlation (see Carrano & Wilson, 2001) The final map was produced with different level of knowledge due to the distribution of tracks and current state of site preservation. Furthermore, it represents a complete documentation that will be used for future work of enhancement, preservation and valorization of the tracksite. The ichnotaxonomical review of the quadrupedal trackways led us to emend the diagnosis of Lavinipes cheminii Avanzini et al. (2003) and to assign several other sparse tracks and trackways to L. chemini. The skeletal reconstruction of fore and hind limbs points towards Gongxianosaurus sp. as the most suitable trackmaker of L. cheminii. The herein supposed Laurasian affinity of the Lavini di Marco dinosaur assemblage clashes with the previous hypotheses that always link the Southern Alps sector with the Gondwana mainland

Hippopotamid dispersal across the Mediterranean in the latest Miocene: A re-evaluation of the Gravitelli record from Sicily, Italy

The first dispersal of Hippopotamidae out of Africa is recorded around 6 Ma, but this event is documented only in a few European localities. Among them, the uppermost Miocene deposits of Gravitelli in Sicily yielded particularly abundant hippopotamid remains. These specimens, published at the beginning of the 20th century, went lost during the 1908 earthquake that destroyed the city of Messina. The specimens from Gravitelli were ascribed to a new species, Hippopotamus siculus; their generic attribution was not questioned during the first half of the past century and they have not been revised in recent decades. The remains of the Gravitelli hippopotamid were mainly represented by isolated teeth and a few postcranial remains. Morphological and dimensional characters of the specimens, such as long lower premolars, lowcrowned molars, a lower canine with longitudinal ridges and a groove on the lateral surface and the overall dimensions suggest that the Sicilian hippopotamid was characterized by plesiomorphic features. The morphology of the specimens collected from Gravitelli is similar to that of Hexaprotodon? crusafonti, Archaeopotamus harvardi, Hexaprotodon sivalensis and Hexaprotodon garyam. Hexaprotodon? siculus is also morphometrically similar to Hexaprotodon sivalensis, but the lower premolars in the former are longer and wider than in the latter. Accordingly, we provisionally refer the Gravitelli hippopotamid to the genus Hexaprotodon. Hexaprotodon? siculus is dimensionally different from the Spanish latest Miocene hippopotamid, herein referred to as Archaeopotamus crusafonti, and the two species are considered as valid taxa. The paleobiogeography of the latest Miocene hippopotamids from the Mediterranean Basin is discussed

A new species of the larger porcelaneous foraminifer Borelis provides novel insights into Neogene to Recent western Pacific palaeobiogeographical dispersal patterns

Only three species of alveolinoidean larger foraminifera occur in present-day tropical shallow-water marine settings. Alveolinella quoyi thrives in the Central Indo-Pacific and Eastern Indo-Pacific, Borelis pulchra in the Central and Eastern Indo-Pacific and in the central Atlantic, whereas Borelis schlumbergeri inhabits the Indo-Pacific Ocean. The northernmost record is that of Alveolinella quoyi from the shallow-water settings in Okinawa (central Ryukyu Islands, Japan). A new porcelaneous larger foraminiferal species, Borelis matsudai sp. nov. (Alveolinoidea, Borelinae), is established herein, based on specimens discovered in present-day shallow-water sediments from Sekisei Lagoon, southern Ryukyu Islands (Japan). This is the northernmost record of the genus in the western Indo-Pacific Warm Pool. The architectural characters of this species suggest its phylogenetic relationship with the Borelis pulchra group. A comprehensive literature survey of fossil and modern records of Borelis pulchra over the past 30 million years shows that the Middle Miocene constriction of the Indonesian Seaway and the Late Miocene–Early Pliocene restriction of the Indonesian Throughflow impacted the species-level dispersal of this species in the Indo-Australian Archipelago. Driven by the Kuroshio dispersal route Borelis matsudai sp. nov. likely appeared in the southern and central Ryukyu Islands at least from the Chibanian (Middle Pleistocene). This species represents a marginal part of a population in significant contact with its ancestor (B. pulchra), which is widespread southward since the Oligocene (Philippines). With ongoing global warming possible occurrences of Borelis matsudai sp. nov. in northern Ryukyu Islands, where it has not yet been found, are expected. The Sekisei Lagoon represents, therefore, a biogeographical stepping stone relay station in northward migration of the shallow-water benthic organisms along the Kuroshio dispersal route

Evaluating the ecological realism of plant species distribution models with ecological indicator values

Species distribution models (SDMs) are routinely applied to assess current as well as future species distributions, for example to assess impacts of future environmental change on biodiversity or to underpin conservation planning. It has been repeatedly emphasized that SDMs should be evaluated based not only on their goodness of fit to the data, but also on the realism of the modelled ecological responses. However, possibilities for the latter are hampered by limited knowledge on the true responses as well as a lack of quantitative evaluation methods. Here we compared modelled niche optima obtained from European-scale SDMs of 1,476 terrestrial vascular plant species with empirical ecological indicator values indicating the preferences of plant species for key environmental conditions. For each plant species we first fitted an ensemble SDM including three modeling techniques (GLM, GAM and BRT) and extracted niche optima for climate, soil, land use and nitrogen deposition variables with a large explanatory power for the occurrence of that species. We then compared these SDM-derived niche optima with the ecological indicator values by means of bivariate correlation analysis. We found weak to moderate correlations in the expected direction between the SDM-derived niche optima and ecological indicator values. The strongest correlation occurred between the modelled optima for growing degree days and the ecological indicator values for temperature. Correlations were weaker for SDM-derived niche optima with a more distal relationship to ecological indicator values (notably precipitation and soil moisture). Further, correlations were consistently highest for BRT, followed by GLM and GAM. Our method gives insight into the ecological realism of modelled niche optima and projected core habitats and can be used to improve SDMs by making a more informed selection of environmental variables and modeling techniques

Attitudes of healthcare professionals and drug regulators about progression-free survival as endpoint in the advanced cancer setting

Purpose: To describe the attitudes of healthcare professionals and drug regulators about progression-free survival (PFS) as efficacy endpoint in clinical trials with patients with advanced cancer and to explore to what extent these attitudes influence the willingness to trade between PFS and toxicity. Methods: Cross-sectional survey with regulators from the European Medicines Agency (EMA), and healthcare professionals (HCP) from the “Stichting Hemato-Oncologie voor Volwassenen Nederland” (HOVON) collaborative group and the European Organisation for Research and Treatment of Cancer (EORTC). Attitudes towards PFS were elicited using 5-point Likert items. The respondents’ willingness to trade between PFS and grade 3 or 4 (G34) toxicity was assessed using the threshold technique and quantified in terms of their maximum acceptable risk (MAR). Results: Responses were collected from 287 HCPs and 64 regulators with mainly clinical expertise. Attitudes towards PFS were often spread out in both groups and related to beliefs about PFS being a likely surrogate for clinical benefit, being an intrinsic benefit to be distinguished from OS, or on the importance given to OS. Being a regulator or holding stronger beliefs about PFS being a likely surrogate or an intrinsic benefit were associated with a higher MAR. Presence of a supportive trend in OS was stated as important but was not associated with MAR. There was agreement on the need to address bias in the adjudication of PFS and the need for improving communication to patients about meaning, strengths, and limitations of improvements in PFS. Conclusion: Attitudes towards PFS were spread out and were associated with individual differences in the willingness to trade between toxicity and PFS. There was agreement on the need to address bias in the adjudication of PFS and improving communication to patients.</p

Multiple Orbitoides d’Orbigny lineages in the Maastrichtian? Data from the Central Sakarya Basin (Turkey) and Arabian Platform successions (Southeastern Turkey and Oman)

The standard reconstruction of species of Orbitoides d’Orbigny into a single lineage during the late Santonian to the end of the Maastrichtian is based upon morphometric data from Western Europe. An irreversible increase in the size of the embryonic apparatus, and the formation of a greater number of epi-embryonic chamberlets (EPC) with time, is regarded as the main evolutionary trends used in species discrimination. However, data from Maastrichtian Orbitoides assemblages from Central Turkey and the Arabian Platform margin (Southeastern Turkey and Oman) are not consistent with this record. The Maastrichtian Besni Formation of the Arabian Platform margin in Southeastern Turkey yields invariably biconvex specimens, with small, tri- to quadrilocular embryons and a small number of EPC, comparable to late Campanian Orbitoides medius (d’Archiac). The upper Maastrichtian Taraklı Formation from the Sakarya Basin of Central Turkey contains two distinct, yet closely associated forms of Orbitoides, easily differentiated by both external and internal features. Flat to biconcave specimens possess a small, tri- to quadrilocular embryonic apparatus of Orbitoides medius-type and a small number of EPC, whereas biconvex specimens possess a large, predominantly bilocular embryonic apparatus, and were assigned to Orbitoides ex. interc. gruenbachensis Papp–apiculatus Schlumberger based on morphometry. The flat to biconcave specimens belong to a long overlooked species Orbitoides pamiri Meriç, originally described from the late Maastrichtian of the Tauride Mountains in SW Turkey. This species is herein interpreted to be an offshoot from the main Orbitoides lineage during the Maastrichtian, as are forms that we term Orbitoides ‘medius’, since they recall this species, yet are younger than normal occurrence with the accepted morphometrically defined lineage. The consistent correlation between the external and internal test features in O. pamiri implies that the shape of the test is not an ecophenotypic variation, but appears to be biologically controlled. We, therefore, postulate that more than one lineage of Orbitoides exists during the Maastrichtian, with a lineage that includes O. ‘medius’ and O. pamiri displaying retrograde evolutionary features

Pakistani children’s experiences of growing up with Beta-Thalassemia Major

In this study, we explored the lived experiences of children with beta-thalassemia major (β-TM). We considered children as experts on their experiences in contrast to the prevalent approach of asking parents or other adults about children’s perspectives. The sample consisted of 12 children aged 8 to12 years. There were two stages to data collection. In Stage 1 we employed two focus group discussions and two role plays and analyzed the data thematically. This directly informed Stage 2, consisting of 12 in-depth interviews subjected to interpretative phenomenological analysis. From our findings we show that living with β-TM involves a continuous struggle between feelings of being different and strategies to minimize these differences to strive for normalcy. We suggest that understanding the experiences of living with β-TM from children’s perspectives can provide unique insights into their experiences, which can fill the gap in the existing, predominantly adult-oriented research on chronic illness

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy

On 21 November 2016, the European Commission issued a marketing authorisation valid throughout the European Union for ixazomib in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Ixazomib was evaluated in one, randomised, double-blind, phase III study comparing ixazomib plus lenalidomide and dexamethasone (n=360; ixazomib arm) versus placebo plus lenalidomide and dexamethasone (n=362; placebo arm) in adult patients with relapsed and/or refractory multiple myeloma who had received at least one prior therapy. The median progression-free survival (PFS) in the intent-to-treat population was 20.6 months in patients treated with ixazomib compared with 14.7 months for patients in the placebo arm (stratified HR=0.742, 95% CI 0.587 to 0.939, stratified p-value=0.012). The most frequently reported adverse reactions (≥20%) within the ixazomib and placebo arms were diarrhoea (42% vs 36%), constipation (34% vs 25%), thrombocytopaenia (28% vs 14%), peripheral neuropathy (28% vs 21%), nausea (26% vs 21%), peripheral oedema (25% vs 18%), vomiting (22% vs 11%) and back pain (21% vs 16%). The scientific review concluded that the gain in PFS of 5.9 months observed with ixazomib was considered clinically meaningful. Concerning the possible uncertainty about the magnitude of the effect, this uncertainty was acceptable given the favourable toxicity profile, and considering that ixazomib is the first agent to allow oral triple combination therapy in this patient population which represents a therapeutic innovation in terms of convenience for patients. Therefore, the benefit-risk for ixazomib in combination with lenalidomide and dexamethasone was considered positive, although the efficacy evidence was not as comprehensive as normally required