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The Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians.
To establish how real-world evidence (RWE) has been used to inform single technology appraisals (STAs) of cancer drugs conducted by the National Institute for Health and Care Excellence (NICE).
STAs published by NICE from April 2011 to October 2018 that evaluated cancer treatments were reviewed. Information regarding the use of RWE to directly inform the company-submitted cost-effectiveness analysis was extracted and categorized by topic. Summary statistics were used to describe emergent themes, and a narrative summary was provided for key case studies.
Materials for a total of 113 relevant STAs were identified and analyzed, of which nearly all (96 percent) included some form of RWE within the company-submitted cost-effectiveness analysis. The most common categories of RWE use concerned the health-related quality of life of patients (71 percent), costs (46 percent), and medical resource utilization (40 percent). While sources of RWE were routinely criticized as part of the appraisal process, we identified only two cases where the use of RWE was overtly rejected; hence, in the majority of cases, RWE was accepted in cancer drug submissions to NICE.
RWE has been used extensively in cancer submissions to NICE. Key criticisms of RWE in submissions to NICE are seldom regarding the use of RWE in general; instead, these are typically concerned with specific data sources and the applicability of these to the decision problem. Within an appropriate context, RWE constitutes an extremely valuable source of information to inform decision making; yet the development of best practice guidelines may improve current reporting standards.
No externally validated tests are available for routine use to confirm clinical diagnosis of major psychiatric disorders. Eye movement abnormalities that distinguish schizophrenia and bipolar disorder have only recently been described. Evidence of oculomotor dysfunction specific to endogenous major depressive disorder (MDD) would represent discovery of a significant endophenotypic interface between psychotic and affective disorders. Out-patients meeting DSM criteria for MDD (n=68, F:M=40:28, median age=49 (IQR 38-57) years) participated in a series of tasks while eye movements were recorded using an EyeLink 1000 infra-red video tracker. Patients' characteristics at time of assessment included median illness duration of 13 years (IQR= 7-23; n=53 available cases), HADS anxiety=11 (IQR 7-15) and depression=9 (IQR 4-11), BDI=27 (IQR 16-33), BPRS= 25 (IQR 20-29) and estimated IQ= 106 (IQR 96-118; n=42). Performance measures from smooth pursuit, picture viewing, and steady fixation were analysed alongside data from controls, schizophrenia, and bipolar disorder cases. A neural network was able to delineate the clinical and control groups with sensitivity=90.4% and specificity=97.1%. Multivariate tests of group differences post hoc revealed that MDD cases were on average poorest in maintaining steady gaze during the fixation task, mirroring the neuropsychological evidence for dysregulation of executive function in prefrontal brain regions. Bipolar and unipolar affective cases performed similarly on smooth pursuit and picture viewing tests, but were systematically different from schizophrenia and control groups. If differences are replicated in further cases, the MDD eye movement marker could be an important tool for psychiatric research, allowing for easier delineation of the major disorders.
Major depressive disorder (MDD) affects at some point in their lives a tenth of the world's population with a higher incidence in females than males. Like all clinical disorders encountered in adult psychiatry, a diagnosis of MDD is symptom-based and has not been externally validated. Eye movement dysfunctions (EMDs) in the functional psychoses have been extensively reported and their potential as biomarkers highlighted but it is unclear whether there are patterns of EMDs specific to MDD. Abnormal EMs in bipolar affective cases have been observed during face and picture viewing, saccadic control and smooth pursuit tasks. However most studies reporting EMs in affective disorders, have not distinguished between unipolar/MDD and bipolar cases. to address this problem we have compared performance on a broad range of EM tests in patients meeting DSM-IV criteria for MDD with identical measures made in a large sample of bipolar, schizophrenia and undiagnosed individuals. Remarkably a network classifier was able to delineate controls and each patient group using EM performance measures with exceptional sensitivity (94%) and specificity (98%). What is more, probability of illness category was not associated with demographic, symptom, neuropsychological or medication variables. It therefore appears that a unique multivariate eye movement phenotype may be associated with MDD. If verified in further MDD cases these findings could be an enormous advance in helping to assess and/or diagnose individuals with symptoms of MDD or at risk of developing MDD.
Uranium–35 wt.% zirconium (U–35 wt.% Zr) alloy was annealed for 1 h and 24 h at 650 °C and characterized to understand the early-stage microstructure evolution. Dendritic microstructure with fine (∼300 nm in length) α-U precipitates clustered between dendrite branches were observed in the 1-h annealed sample. After 24-h annealing at 650 °C, the α-U precipitates coarsened, and the dendritic microstructure disappeared because of microstructure homogenization. Furthermore, microchemical homogenization observed with energy-dispersive X-ray spectroscopy analysis suggests that α-U precipitates are approaching thermodynamic equilibrium in the 24-h annealed sample. The findings from this study have potential impacts on the manufacturing and computer modeling of metallic nuclear fuel.
This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer’s disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.
This study examines the factors influencing friendship quality during emergent adulthood. Data were collected on a sample of 393 college students (age range 18–22, M = 20.01). Nine multi-item measures were used as indicators in this study. Seven scales were drawn from the Battery of Adolescent Measures (Benson & Faas, 2014). The other two were the pragmatic (social) language and the aloof scales, which provided sensitised assessment of interpersonal deficits (Hurley, Losh, Parlier, Reznick, & Piven, 2007). The article hypothesises that family warmth predicts friendship quality during emergent adulthood. It also hypothesises that this relationship is mediated by emergent adults’ self-perceptions and by their social competence. Structural equation models supported the first hypothesis and also showed that self-perceptions and social competence partially mediate the main relationship. We also examined each mediator separately for evidence of partial mediation, but the full model remained a significantly better fit to the data compared to both single mediator models.
The Main Karoo Basin of South Africa contains a near-continuous sequence of continental deposition spanning ~80 Myr from the mid-Permian to the Early Jurassic. The terrestrial vertebrates of this sequence provide a high-resolution stratigraphic record of regional origination and extinction, especially for the mid–late Permian. Until now, data have only been surveyed at coarse stratigraphic resolution using methods that are biased by nonuniform sampling rates, limiting our understanding of the dynamics of diversification through this important time period. Here, we apply robust methods (gap-filler and modified gap-filler rates) for the inference of patterns of species richness, origination rates, and extinction rates to a subset of 1321 reliably-identified fossil occurrences resolved to approximately 50 m stratigraphic intervals. This data set provides an approximate time resolution of 0.3–0.6 Myr and shows that extinction rates increased considerably in the upper 100 m of the mid-Permian Abrahamskraal Formation, corresponding to the latest part of the Tapinocephalus Assemblage Zone (AZ). Origination rates were only weakly elevated in the same interval and were not sufficient to compensate for these extinctions. Subsampled species richness estimates for the lower part of the overlying Teekloof Formation (corresponding to the Pristerognathus and Tropidostoma AZs) are low, showing that species richness remained low for at least 1.5–3 million years after the main extinction pulse. A high unevenness of the taxon abundance–frequency distribution, which is classically associated with trophically unstable postextinction faunas, in fact developed shortly before the acme of elevated extinction rates due to the appearance and proliferation of the dicynodont Diictodon. Our findings provide strong support for a Capitanian (“end-Guadalupian”) extinction event among terrestrial vertebrates and suggest that further high-resolution quantitative studies may help resolve the lack of consensus among paleobiologists regarding this event.