Growth, age and size of the Jurassic pachycormid Leedsichthys problematicus (Osteichthyes: Actinopterygii)

The Jurassic pachycormid osteichthyan Leedsichthys problematicus is renowned for having been able to achieve prodigious size for a bony fish. Building on work of MARTILL (1986a), a thorough examination of all known material was conducted in order to constrain estimates of the size of this animal and examine its rate of growth. Important specimens of Leedsichthys are described for the first time. The histology of Leedsichthys is reviewed, and the presence of growth annuli is used to establish ages for five specimens. Age and growth data were obtained from gill rakers (n = 4) and lepidotrichia (n = 2). Lepidotrichia show upward curvilinear growth profiles and ages ranging from 21 to 40 annuli, which are assumed to represent years. Both growth profiles start at a small size (0.26 and 0.33 mm radial distance), which is assumed to represent age 1. However, annuli can be lost near the margins of the elements. Gill rakers exhibit a sigmoidal growth profile. Age of gill rakers was estimated by adjusting the alignment of the inflection points of the growth profiles thereby giving adjusted ages. Gill rakers ranged in age from 19–38 annuli, but all show evidence of reabsorption of annuli near the focal points and at the margins of most elements. Sizes for the five individuals range from 8.0-16.5 m for ages of 19-40 years. Growth rate (0.01-0.05 K) was relatively slow as expected for a large, long-lived fish. At age 1, individuals were 1.6 m in length. Estimates for the length of L. problematicus compare well with published lengths of other large suspension feeders such as those for basking and whale sharks

Design of a global soil moisture initialization procedure for the simple biosphere model

Global soil moisture and land-surface evapotranspiration fields are computed using an analysis scheme based on the Simple Biosphere (SiB) soil-vegetation-atmosphere interaction model. The scheme is driven with observed precipitation, and potential evapotranspiration, where the potential evapotranspiration is computed following the surface air temperature-potential evapotranspiration regression of Thomthwaite (1948). The observed surface air temperature is corrected to reflect potential (zero soil moisture stress) conditions by letting the ratio of actual transpiration to potential transpiration be a function of normalized difference vegetation index (NDVI). Soil moisture, evapotranspiration, and runoff data are generated on a daily basis for a 10-year period, January 1979 through December 1988, using observed precipitation gridded at a 4 deg by 5 deg resolution

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

Investigating the feasibility and acceptability of the HOLOBalance system compared with standard care in older adults at risk for falls: study protocol for an assessor blinded pilot randomised controlled study

INTRODUCTION: Approximately one in three of all older adults fall each year, with wide ranging physical, psychosocial and healthcare-related consequences. Exercise-based interventions are the cornerstone for falls prevention programmes, yet these are not consistently provided, do not routinely address all components of the balance system and are often not well attended. The HOLOBalance system provides an evidence-based balance training programme delivered to patients in their home environment using a novel technological approach including an augmented reality virtual physiotherapist, exergames and a remote monitoring system. The aims of this proof-of-concept study are to (1) determine the safety, acceptability and feasibility of providing HOLOBalance to community dwelling older adults at risk for falls and (2) provide data to support sample size estimates for a future trial. METHODS: A single (assessor) blinded pilot randomised controlled proof of concept study. 120 participants will be randomised to receive an 8-week home exercise programme consisting of either: (1) HOLOBalance or (2) The OTAGO Home Exercise Programme. Participants will be required to complete their exercise programme independently under the supervision of a physiotherapist. Participants will have weekly telephone contact with their physiotherapist, and will receive home visits at weeks 0, 3 and 6. Outcome measures of safety, acceptability and feasibility, clinical measures of balance function, disability, balance confidence and cognitive function will be assessed before and immediately after the 8 week intervention. Acceptability and feasibility will be explored using descriptive statistics, and trends for effectiveness will be explored using general linear model analysis of variance. ETHICS AND DISSEMINATION: This study has received institutional ethical approvals in Germany (reference: 265/19), Greece (reference: 9769/24-6-2019) and the UK (reference: 19/LO/1908). Findings from this study will be submitted for peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04053829. PROTOCOL VERSION: V.2, 20 January 2020

How is rehabilitation with and without an integrated self-management approach perceived by UK community-dwelling stroke survivors? A qualitative process evaluation to explore implementation and contextual variations.

OBJECTIVE: Self-management programmes could support long-term needs after stroke and using methods integrated into rehabilitation is one option. To explore theoretical assumptions and possible mechanisms of implementation a process evaluation was delivered alongside a cluster trial which has demonstrated feasibility of an integrated self-management programme (Bridges SMP) in community-dwelling stroke survivors. This paper aims to show the extent to which experiences from stroke survivors receiving rehabilitation in control (usual care) and intervention (integrated self-management) sites reflected the differences in rehabilitation received and whether their understandings aligned with the self-management approach employed. DESIGN: Semistructured qualitative interviews carried out as part of a process evaluation analysed thematically. SETTING: Study was based in South London; all interviews were carried out in participants' home setting. PARTICIPANTS: 22 stroke participants recruited; 12 from integrated self-management sites and 10 from usual care sites. RESULTS: All participants revealed shared appreciation of knowledge and support from therapists but subtle differences emerged between sites in respect to perceptions about responsibility, control and how previous experiences were used. Accounts depicted a variance regarding who had structured and planned their rehabilitation, with greater flexibility about content and involvement perceived by participants from the integrated self-management sites. They also provided accounts and experiences which aligned with principles of the intervention, such as self-discovery and problem-solving. CONCLUSIONS: The findings reflect our theoretical assumptions and possible mechanisms of implementation that rehabilitation with a focus on supporting self-management is reflected in accounts and understandings of stroke survivors. Taken together with our previous research this justifies evaluating the effectiveness of Bridges SMP in a larger sample to further contribute to an understanding of the functioning of the intervention, implementation, contextual factors and mechanisms of impact. TRIAL REGISTRATION NUMBER: ISRCTN42534180; Post-results

Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling

BACKGROUND T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain RESULTS Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. CONCLUSION The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.This work was supported by grants from the NHMRC and the Juvenile Diabetes Research Foundation

Silencing of the XAF1 gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-β

BACKGROUND: XIAP-associated factor 1 (XAF1) is a putative tumor suppressor that exerts its proapoptotic effects through both caspase-dependent and – independent means. Loss of XAF1 expression through promoter methylation has been implicated in the process of tumorigenesis in a variety of cancers. In this report, we investigated the role of basal xaf1 promoter methylation in xaf1 expression and assessed the responsiveness of cancer cell lines to XAF1 induction by IFN-β. METHODS: We used the conventional bisulfite DNA modification and sequencing method to determine the methylation status in the CpG sites of xaf1 promoter in glioblastoma (SF539, SF295), neuroblastoma (SK-N-AS) and cervical carcinoma (HeLa) cells. We analysed the status and incidence of basal xaf1 promoter methylation in xaf1 expression in non-treated cells as well as under a short or long exposure to IFN-β. Stable XAF1 glioblastoma knock-down cell lines were established to characterize the direct implication of XAF1 in IFN-β-mediated sensitization to TRAIL-induced cell death. RESULTS: We found a strong variability in xaf1 promoter methylation profile and responsiveness to IFN-β across the four cancer cell lines studied. At the basal level, aberrant promoter methylation was linked to xaf1 gene silencing. After a short exposure, the IFN-β-mediated reactivation of xaf1 gene expression was related to the degree of basal promoter methylation. However, in spite of continued promoter hypermethylation, we find that IFN-β induced a transient xaf1 expression, that in turn, was followed by promoter demethylation upon a prolonged exposure. Importantly, we demonstrated for the first time that IFN-β-mediated reactivation of endogenous XAF1 plays a critical role in TRAIL-induced cell death since XAF1 knock-down cell lines completely lost their IFN-β-mediated TRAIL sensitivity. CONCLUSION: Together, these results suggest that promoter demethylation is not the sole factor determining xaf1 gene induction under IFN-β treatment. Furthermore, our study provides evidence that XAF1 is a crucial interferon-stimulated gene (ISG) mediator of IFN-induced sensitization to TRAIL in cancer

An Evaluation of Putative Sympatric Speciation within Limnanthes (Limnanthaceae)

Limnanthes floccosa ssp. floccosa and L. floccosa ssp. grandiflora are two of five subspecies within Limnanthes floccosa endemic to vernal pools in southern Oregon and northern California. Three seasons of monitoring natural populations have quantified that L. floccosa ssp. grandiflora is always found growing sympatrically with L. floccosa ssp. floccosa and that their flowering times overlap considerably. Despite their subspecific rank within the same species crossing experiments have confirmed that their F1 hybrids are sterile. An analysis of twelve microsatellite markers, with unique alleles in each taxon, also shows exceedingly low levels of gene flow between populations of the two subspecies. Due to the lack of previous phylogenetic resolution among L. floccosa subspecies, we used Illumina next generation sequencing to identify single nucleotide polymorphisms from genomic DNA libraries of L. floccosa ssp. floccosa and L. floccosa ssp. grandiflora. These data were used to identify single nucleotide polymorphisms in the chloroplast, mitochondrial, and nuclear genomes. From these variable loci, a total of 2772 bp was obtained using Sanger sequencing of ten individuals representing all subspecies of L. floccosa and an outgroup. The resulting phylogenetic reconstruction was fully resolved. Our results indicate that although L. floccosa ssp. floccosa and L. floccosa ssp. grandiflora are closely related, they are not sister taxa and therefore likely did not diverge as a result of a sympatric speciation event

A Dynamic Bayesian Network Approach to Behavioral Modelling of Elderly People during a Home-based Augmented Reality Balance Physiotherapy Programme

In this study, we propose a dynamic Bayesian network (DBN)-based approach to behavioral modelling of community dwelling older adults at risk for falls during the daily sessions of a hologram-enabled vestibular rehabilitation therapy programme. The component of human behavior being modelled is the level of frustration experienced by the user at each exercise, as it is assessed by the NASA Task Load Index. Herein, we present the topology of the DBN and test its inference performance on real-patient data.Clinical Relevance- Precise behavioral modelling will provide an indicator for tailoring the rehabilitation programme to each individual's personal psychological needs