A new small-bodied azhdarchoid pterosaur from the Lower Cretaceous of England and its implications for pterosaur anatomy, diversity and phylogeny

BACKGROUND: Pterosaurs have been known from the Cretaceous sediments of the Isle of Wight (southern England, United Kingdom) since 1870. We describe the three-dimensional pelvic girdle and associated vertebrae of a small near-adult pterodactyloid from the Atherfield Clay Formation (lower Aptian, Lower Cretaceous). Despite acknowledged variation in the pterosaur pelvis, previous studies have not adequately sampled or incorporated pelvic characters into phylogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: The new specimen represents the new taxon Vectidraco daisymorrisae gen. et sp. nov., diagnosed by the presence of a concavity posterodorsal to the acetabulum and the form of its postacetabular process on the ilium. Several characters suggest that Vectidraco belongs to Azhdarchoidea. We constructed a pelvis-only phylogenetic analysis to test whether the pterosaur pelvis carries a useful phylogenetic signal. Resolution in recovered trees was poor, but they approximately matched trees recovered from analyses of total evidence. We also added Vectidraco and our pelvic characters to an existing total-evidence matrix for pterosaurs. Both analyses recovered Vectidraco within Azhdarchoidea. CONCLUSIONS/ SIGNIFICANCE: The Lower Cretaceous strata of western Europe have yielded members of several pterosaur lineages, but Aptian pterosaurs from western Europe are rare. With a pelvis length of 40 mm, the new animal would have had a total length of c. 350 mm, and a wingspan of c. 750 mm. Barremian and Aptian pterodactyloids from western Europe show that small-bodied azhdarchoids lived alongside ornithocheirids and istiodactylids. This assemblage is similar in terms of which lineages are represented to the coeval beds of Liaoning, China; however, the number of species and specimens present at Liaoning is much higher. While the general phylogenetic composition of western European and Chinese communities appear to have been approximately similar, the differences may be due to different palaeoenvironmental and depositional settings. The western Europe pterodactyloid record may therefore be artificially low in diversity due to preservational factors

Recovery from Posttraumatic Stress Symptoms: A Qualitative Study of Attributions in Survivors of War

This study was funded by a grant from the European Commission, contract number INCO-CT-2004-50917

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes

Aims: Biomarker‐driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub‐classify iMB, and proffer strategies for personalized, risk‐adapted therapies. Methods: We characterized the iMB molecular landscape, including second‐generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). Results: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second‐generation subtypes II/III/IV. Subtype II strongly associated with large‐cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very‐high‐risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4) and subtype IV tumours were standard risk (80% OS) using upfront CSI‐based therapies; randomized‐controlled trials of upfront radiation‐sparing and/or second‐line radiotherapy should be considered. Seventy‐five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non‐DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH. iMBSHH harboured two distinct subtypes (iMBSHH‐I/II). Within the discriminated favourable‐risk iMBSHH DN/MBEN patient group, iMBSHH‐II had significantly better progression‐free survival than iMBSHH‐I, offering opportunities for risk‐adapted stratification of upfront therapies. Both iMBSHH‐I and iMBSHH‐II showed notable rescue rates (56% combined post‐relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. Conclusions: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup‐dependent survival models highlight opportunities for biomarker‐directed therapies

Heterostructured electrode with concentration gradient shell for highly efficient oxygen reduction at low temperature

Heterostructures of oxides have been widely investigated in optical, catalytic and electrochemical applications, because the heterostructured interfaces exhibit pronouncedly different transport, charge, and reactivity characteristics compared to the bulk of the oxides. Here we fabricated a three-dimensional (3D) heterostructured electrode with a concentration gradient shell. The concentration gradient shell with the composition of Ba0.5-xSr0.5-yCo0.8Fe0.2O3-δ (BSCF-D) was prepared by simply treating porous Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) backbone with microwave-plasma. Electrochemical impedance spectroscopy reveals that the oxygen surface exchange rate of the BSCF-D is enhanced by ~250% that of the pristine BSCF due to the appearance of the shell. The heterostructured electrode shows an interfacial resistance as low as 0.148 Ω cm2 at 550°C and an unchanged electrochemical performance after heating treatment for 200 h. This method offers potential to prepare heterostructured oxides not only for electrochemical devices but also for many other applications that use ceramic materials

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Gastrointestinal nematode infections in German sheep

The objective of the present study was to determine the prevalence and variation of natural gastrointestinal nematode (GIN) infections in lambs according to birth type, gender and breed based on individual faecal egg counts (FEC) from various regions in Germany. A total of 3,924 lambs (3 to 15 months old) with different genetic backgrounds (Merinoland, German Blackhead Mutton, Rhoen, Texel and Merino long-wool) were individually sampled during the grazing period between 2006 and 2008. Furthermore, pooled faecal samples from each of the farms were cultured in order to differentiate the third-stage larvae of the nematode spp. Sixty-three percent of the lambs were infected with GIN. The infections were mostly low to moderate and involved several nematode species. The Trichostrongylus spp. was the predominant species based on the percentage of larvae in faecal cultures. Only 11.4% of the lambs were free of Eimeria oocysts. Tapeworm eggs were encountered in 13.2% of all samples. The prevalence of GIN infections varied significantly (P < 0.001) among farms. A significantly higher FEC (P < 0.05) was observed in multiple-born lambs when compared with singletons. Moreover, male lambs were more susceptible to infection than females (P < 0.001). No significant differences (P > 0.05) were observed between breeds regarding FEC. Inter-individual variations were higher than inter-breed differences, which may indicate the possibility of selection within these breeds for parasites resistance as described in earlier studies

Broader Neutralizing Antibodies against H5N1 Viruses Using Prime-Boost Immunization of Hyperglycosylated Hemagglutinin DNA and Virus-Like Particles

BACKGROUND: Highly pathogenic avian influenza (HPAI) H5N1 viruses and their transmission capability from birds to humans have raised global concerns about a potential human pandemic. The inherent nature of antigenic changes in influenza viruses has not been sufficiently taken into account in immunogen designs for broadly protective HPAI H5N1 vaccines. METHODS: We designed a hyperglycosylated HA vaccine using N-linked glycan masking on highly variable sequences in the HA1 globular head. Immunization of these hyperglycosylated HA DNA vaccines followed by a flagellin-containing virus-like particle booster in mice was conducted to evaluate neutralizing antibody responses against various clades of HPAI H5N1 viruses. RESULTS: We introduced nine N-X-S/T motifs in five HA1 regions: 83NNT, 86NNT, 94NFT, 127NSS, 138NRT, 156NTT, 161NRS, 182NDT, and 252NAT according to sequence alignment analyses from 163 HPAI H5N1 human isolates. Although no significant differences of anti-HA total IgG titers were found with these hyperglycosyalted HA compared to the wild-type control, the 83NNT and 127NSS mutants elicited significantly potent cross-clade neutralizing antibodies against HPAI H5N1 viruses. CONCLUSIONS: This finding may have value in terms of novel immunogen design for developing cross-protective H5N1 vaccines

On the Size and Flight Diversity of Giant Pterosaurs, the Use of Birds as Pterosaur Analogues and Comments on Pterosaur Flightlessness

The size and flight mechanics of giant pterosaurs have received considerable research interest for the last century but are confused by conflicting interpretations of pterosaur biology and flight capabilities. Avian biomechanical parameters have often been applied to pterosaurs in such research but, due to considerable differences in avian and pterosaur anatomy, have lead to systematic errors interpreting pterosaur flight mechanics. Such assumptions have lead to assertions that giant pterosaurs were extremely lightweight to facilitate flight or, if more realistic masses are assumed, were flightless. Reappraisal of the proportions, scaling and morphology of giant pterosaur fossils suggests that bird and pterosaur wing structure, gross anatomy and launch kinematics are too different to be considered mechanically interchangeable. Conclusions assuming such interchangeability—including those indicating that giant pterosaurs were flightless—are found to be based on inaccurate and poorly supported assumptions of structural scaling and launch kinematics. Pterosaur bone strength and flap-gliding performance demonstrate that giant pterosaur anatomy was capable of generating sufficient lift and thrust for powered flight as well as resisting flight loading stresses. The retention of flight characteristics across giant pterosaur skeletons and their considerable robustness compared to similarly-massed terrestrial animals suggest that giant pterosaurs were not flightless. Moreover, the term ‘giant pterosaur’ includes at least two radically different forms with very distinct palaeoecological signatures and, accordingly, all but the most basic sweeping conclusions about giant pterosaur flight should be treated with caution. Reappraisal of giant pterosaur material also reveals that the size of the largest pterosaurs, previously suggested to have wingspans up to 13 m and masses up to 544 kg, have been overestimated. Scaling of fragmentary giant pterosaur remains have been misled by distorted fossils or used inappropriate scaling techniques, indicating that 10–11 m wingspans and masses of 200–250 kg are the most reliable upper estimates of known pterosaur size