Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia

AbstractTibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadherin and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects than previously thought

Upper Body-Based Power Wheelchair Control Interface for Individuals with Tetraplegia

Many power wheelchair control interfaces are not sufficient for individuals with severely limited upper limb mobility. The majority of controllers that do not rely on coordinated arm and hand movements provide users a limited vocabulary of commands and often do not take advantage of the user's residual motion. We developed a body-machine interface (BMI) that leverages the flexibility and customizability of redundant control by using high dimensional changes in shoulder kinematics to generate proportional control commands for a power wheelchair. In this study, three individuals with cervical spinal cord injuries were able to control a power wheelchair safely and accurately using only small shoulder movements. With the BMI, participants were able to achieve their desired trajectories and, after five sessions driving, were able to achieve smoothness that was similar to the smoothness with their current joystick. All participants were twice as slow using the BMI however improved with practice. Importantly, users were able to generalize training controlling a computer to driving a power wheelchair, and employed similar strategies when controlling both devices. Overall, this work suggests that the BMI can be an effective wheelchair control interface for individuals with high-level spinal cord injuries who have limited arm and hand control

Optimal leverage from non-ergodicity

In modern portfolio theory, the balancing of expected returns on investments against uncertainties in those returns is aided by the use of utility functions. The Kelly criterion offers another approach, rooted in information theory, that always implies logarithmic utility. The two approaches seem incompatible, too loosely or too tightly constraining investors' risk preferences, from their respective perspectives. The conflict can be understood on the basis that the multiplicative models used in both approaches are non-ergodic which leads to ensemble-average returns differing from time-average returns in single realizations. The classic treatments, from the very beginning of probability theory, use ensemble-averages, whereas the Kelly-result is obtained by considering time-averages. Maximizing the time-average growth rates for an investment defines an optimal leverage, whereas growth rates derived from ensemble-average returns depend linearly on leverage. The latter measure can thus incentivize investors to maximize leverage, which is detrimental to time-average growth and overall market stability. The Sharpe ratio is insensitive to leverage. Its relation to optimal leverage is discussed. A better understanding of the significance of time-irreversibility and non-ergodicity and the resulting bounds on leverage may help policy makers in reshaping financial risk controls.Comment: 17 pages, 3 figures. Updated figures and extended discussion of ergodicit

The challenge of enterprise/innovation: a case study of a modern university

In the prevailing economic and political climate for Higher Education a greater emphasis has been placed on diversifying the funding base. The present study was undertaken between 2012 and 2014 and addressed the implementation of an approach to the transformation of one academic school in a medium-sized modern university in Wales to a more engaged enterprise culture. A multimethod investigation included a bi-lingual (English and Welsh) online survey of academic staff and yielded a 71% response rate (n = 45). The findings informed a series of in-depth interviews (n = 24) with a representative sample of those involved in enterprise work (support staff, managers, senior managers), and those who were not. The results provided the platform for the ‘S4E model’ for effective engagement with enterprise: (1) Strategic significance for Enterprise, (2) Support for Enterprise, (3) Synergy for Enterprise, and (4) Success for Enterprise. The outcomes of the research and the recommendations from it have potential to inform practice in other academic schools within the university and, in a wider context, within other Schools of Education regionally, nationally and internationally. Its original empirical exploration of enterprise within education studies is a significant contribution to that body of knowledge

High-resolution observations in the western Mediterranean Sea: the REP14-MED experiment

The observational part of the REP14-MED experiment was conducted in June 2014 in the Sardo-Balearic Basin west of Sardinia (western Mediterranean Sea). Two research vessels collected high-resolution oceanographic data by means of hydrographic casts, towed systems, and underway measurements. In addition, a vast amount of data was provided by a fleet of 11 ocean gliders, time series were available from moored instruments, and information on Lagrangian flow patterns was obtained from surface drifters and one profiling float. The spatial resolution of the observations encompasses a spectrum over 4 orders of magnitude from (10¹ m) to (10⁵ m), and the time series from the moored instruments cover a spectral range of 5 orders from (10¹ s) to (10⁶ s). The objective of this article is to provide an overview of the huge data set which has been utilised by various studies, focusing on (i) water masses and circulation, (ii) operational forecasting, (iii) data assimilation, (iv) variability of the ocean, and (v) new payloads for gliders

A randomised feasibility study to investigate the impact of education and the addition of prompts on the sedentary behaviour of office workers

Abstract Background Office workers have been identified as being at risk of accumulating high amounts of sedentary time in prolonged events during work hours, which has been associated with increased risk of a number of long-term health conditions. There is some evidence that providing advice to stand at regular intervals during the working day, and using computer-based prompts, can reduce sedentary behaviour in office workers. However, evidence of effectiveness, feasibility and acceptability for these types of intervention is currently limited. Methods A 2-arm, parallel group, cluster-randomised feasibility trial to assess the acceptability of prompts to break up sedentary behaviour was conducted with office workers in a commercial bank (n = 21). Participants were assigned to an education only group (EG) or prompt and education group (PG). Both groups received education on reducing and breaking up sitting at work, and the PG also received hourly prompts, delivered by Microsoft Outlook over 10 weeks, reminding them to stand. Objective measurements of sedentary behaviour were made using activPAL monitors worn at three time points: baseline, in the last 2 weeks of the intervention period and 12 weeks after the intervention. Focus groups were conducted to explore the acceptability of the intervention and the motivations and barriers to changing sedentary behaviour. Results Randomly generated, customised prompts, delivered by Microsoft Outlook, with messages about breaking up sitting, proved to be a feasible and acceptable way of delivering prompts to office workers. Participants in both groups reduced their sitting, but changes were not maintained at follow-up. The education session seemed to increase outcome expectations of the benefits of changing sedentary behaviour and promote self-regulation of behaviour in some participants. However, low self-efficacy and a desire to conform to cultural norms were barriers to changing behaviour. Conclusions Prompts delivered by Microsoft Outlook were a feasible, low-cost way of prompting office workers to break up their sedentary behaviour, although further research is needed to determine whether this has an additional impact on sedentary behaviour, to education alone. The role of cultural norms, and promoting self-efficacy, should be considered in the design of future interventions. Trial registration This study was registered retrospectively as a clinical trial on ClinicalTrials.gov (ID no. NCT02609282 ) on 23 March 2015

Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

Abstract Background During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks’ gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction. Methods Data were analysed from 548 antenatal visits after 20 weeks’ gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction. Results There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia. Conclusions Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

VERTICO VI: Cold-gas asymmetries in Virgo cluster galaxies

We analyze cold-gas distributions in Virgo cluster galaxies using resolved CO(2-1) (tracing molecular hydrogen, H2) and HI observations from the Virgo Environment Traced In CO (VERTICO) and the VLA Imaging of Virgo in Atomic Gas (VIVA) surveys. From a theoretical perspective, it is expected that environmental processes in clusters will have a stronger influence on diffuse atomic gas compared to the relatively dense molecular gas component, and that these environmental perturbations can compress the cold interstellar medium in cluster galaxies leading to elevated star formation. In this work we observationally test these predictions for star-forming satellite galaxies within the Virgo cluster. We divide our Virgo galaxy sample into HI-normal, HI-tailed, and HI-truncated classes and show, unsurprisingly, that the HI-tailed galaxies have the largest quantitative HI asymmetries. We also compare to a control sample of non-cluster galaxies and find that Virgo galaxies, on average, have HI asymmetries that are 40 +/- 10 per cent larger than the control. There is less separation between control, HI-normal, HI-tailed, and HI-truncated galaxies in terms of H2 asymmetries, and on average, Virgo galaxies have H2 asymmetries that are only marginally (20 +/- 10 per cent) larger than the control sample. We find a weak correlation between HI and H2 asymmetries over our entire sample, but a stronger correlation for those specific galaxies being strongly impacted by environmental perturbations. Finally, we divide the discs of the HI-tailed Virgo galaxies into a leading half and trailing half according to the observed tail direction. We find evidence for excess molecular gas mass on the leading halves of the disc. This excess molecular gas on the leading half is accompanied by an excess in star formation rate such that the depletion time is, on average, unchanged.Comment: 15 pages, 8 figures, 1 table, accepted for publication in A&