Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis

The distribution of pond snail communities across a landscape: separating out the influence of spatial position from local habitat quality for ponds in south-east Northumberland, UK

Ponds support a rich biodiversity because the heterogeneity of individual ponds creates, at the landscape scale, a diversity of habitats for wildlife. The distribution of pond animals and plants will be influenced by both the local conditions within a pond and the spatial distribution of ponds across the landscape. Separating out the local from the spatial is difficult because the two are often linked. Pond snails are likely to be affected by both local conditions, e.g. water hardness, and spatial patterns, e.g. distance between ponds, but studies of snail communities struggle distinguishing between the two. In this study, communities of snails were recorded from 52 ponds in a biogeographically coherent landscape in north-east England. The distribution of snail communities was compared to local environments characterised by the macrophyte communities within each pond and to the spatial pattern of ponds throughout the landscape. Mantel tests were used to partial out the local versus the landscape respective influences. Snail communities became more similar in ponds that were closer together and in ponds with similar macrophyte communities as both the local and the landscape scale were important for this group of animals. Data were collected from several types of ponds, including those created on nature reserves specifically for wildlife, old field ponds (at least 150 years old) primarily created for watering livestock and subsidence ponds outside protected areas or amongst coastal dunes. No one pond type supported all the species. Larger, deeper ponds on nature reserves had the highest numbers of species within individual ponds but shallow, temporary sites on farm land supported a distinct temporary water fauna. The conservation of pond snails in this region requires a diversity of pond types rather than one idealised type and ponds scattered throughout the area at a variety of sites, not just concentrated on nature reserves

Recognising facial expressions in video sequences

We introduce a system that processes a sequence of images of a front-facing human face and recognises a set of facial expressions. We use an efficient appearance-based face tracker to locate the face in the image sequence and estimate the deformation of its non-rigid components. The tracker works in real-time. It is robust to strong illumination changes and factors out changes in appearance caused by illumination from changes due to face deformation. We adopt a model-based approach for facial expression recognition. In our model, an image of a face is represented by a point in a deformation space. The variability of the classes of images associated to facial expressions are represented by a set of samples which model a low-dimensional manifold in the space of deformations. We introduce a probabilistic procedure based on a nearest-neighbour approach to combine the information provided by the incoming image sequence with the prior information stored in the expression manifold in order to compute a posterior probability associated to a facial expression. In the experiments conducted we show that this system is able to work in an unconstrained environment with strong changes in illumination and face location. It achieves an 89\% recognition rate in a set of 333 sequences from the Cohn-Kanade data base

Hybrid endoscopic thymectomy : combined transesophageal and transthoracic approach in a survival porcine model with cadaver assessment

BACKGROUND: Video-assisted thoracoscopic surgery thymectomy has been used in the treatment of Myastenia Gravis and thymomas (coexisting or not). In natural orifice transluminal endoscopic surgery, new approaches to the thorax are emerging as alternatives to the classic transthoracic endoscopic surgery. The aim of this study was to assess the feasibility and reliability of hybrid endoscopic thymectomy (HET) using a combined transthoracic and transesophageal approach. METHODS: Twelve consecutive in vivo experiments were undertaken in the porcine model (4 acute and 8 survival). The same procedure was assessed in a human cadaver afterward. For HET, an 11-mm trocar was inserted in the 2nd intercostal space in the left anterior axillary line. A 0° 10-mm thoracoscope with a 5-mm working channel was introduced. Transesophageal access was created through a submucosal tunnel using a flexible gastroscope with a single working channel introduced through the mouth. Using both flexible (gastroscope) and rigid (thoracoscope) instruments, the mediastinum was opened; the thymus was dissected, and the vessels were ligated using electrocautery alone. RESULTS: Submucosal tunnel creation and esophagotomy were performed safely without incidents in all animals. Complete thymectomy was achieved in all experiments. All animals in the survival group lived for 14 days. Thoracoscopic and postmortem examination revealed pleural adhesions on site of the surgical procedure with no signs of infection. Histological analysis of the proximal third of the esophagus revealed complete cicatrization of both mucosal defect and myotomy site. In the human cadaver, we were able to replicate all the procedure even though we were not able to identify the thymus. CONCLUSIONS: Hybrid endoscopic thymectomy is feasible and reliable. HET could be regarded as a possible alternative to classic thoracoscopic approach for patients requiring thymectomy.This project was funded by the FCT Grants project PTDC/SAU-OSM/105578/2008

Race-Level Reporting of Incidents Using an Online System during Three Seasons (2019/2020-2021/2022) of Thoroughbred Flat Racing in New Zealand

In the 2019/20 Thoroughbred racing season, the paper-based reporting process of stipendiary steward reports was upgraded to an online system ('Infohorse database') to allow for the rapid entry of precise event and injury data. The objectives of this study were to describe the incident and non-incident examinations during the 2019/20, 2020/21, and 2021/22 Thoroughbred flat racing seasons in New Zealand and describe the primary injury and reporting outcomes. The introduction of the online system was associated with fewer miscoding events with horse identification (0.1%). An improvement in the definition and prompts in reporting within the online system compared with the previous paper-based system resulted in a greater frequency of non-incident examinations being undertaken. The increased frequency of reporting the clinical outcome, 'no observable abnormalities detected' (NOAD), demonstrates the role of stipendiary stewards to carry out routine screening. The frequency of most clinical findings, such as musculoskeletal fractures (0.5 per 1000 starts, 95% CI = 0.3-0.6), remained similar compared to previously reported data using the paper-based system. The online system provided a more structured dataset compared with the paper-based system, making it a useful tool for the monitoring of incidents, injuries, and potential risk factors within Thoroughbred racing in New Zealand. Therefore, evidence-based changes to the management and structure of racing can be undertaken to ensure the industry meets its duty of care for racehorse and jockey welfare.fals

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Risk Factors for Horse Fatality in Thoroughbred Jumps Racing in New Zealand.

The aim of this study was to examine the race-, horse- and jockey-level risk factors for race day fatality in New Zealand Thoroughbred jumps racing using retrospective race day data from the 2011/12 to 2021/22 seasons (n = 8,970 starts). There were 51 race day fatalities resulting in an incidence rate of 5.7 per 1,000 starts (95% C.I. 4.3-7.5). The majority of fatalities were the result of fractures (44/51, 4.9 per 1,000 starts, 95% C.I. 3.7-6.6). Steeplechase and hurdle races had the same incidence of fatal fractures of 4.9 per 1,000 starts (95% C.I. 3.7-6.6, P > .05). Most (70.5%) of the fatal fractures were due to a horse falling during the race. In steeplechase races, horses running in races over 4,201 m were 5.0 times (95% C.I. 1.2-33.0) more likely to sustain a fatal fracture than horses in racing over shorter distances. In hurdle races, horses racing during spring were 2.2 times (95% C.I. 1.0-4.8) more likely to sustain a fatal fracture compared to winter. Due to the low number of suspected cardiac failures and fatal soft tissue injuries, risk factors for these fatalities could not be identified. These data provide a baseline to enable evidence-based regulatory changes and prospectively monitor the effectiveness of changes made.fals

Race-Level Reporting of Incidents during Two Seasons (2015/16 to 2016/17) of Thoroughbred Flat Racing in New Zealand.

The objective of this study was to describe the incident and non-incident reports of Thoroughbred flat racing in New Zealand. Retrospective stipendiary stewards' reports of race day events during the 2015/2016 and 2016/2017 racing season were examined. The primary injury and reporting outcomes were analysed to assess the horse- and race-level risk factors associated with the occurrence of incident and non-incident reports. The number of incident and non-incident events and binomial exact 95% confidence intervals were calculated per 1000 horse starts. Most reports were for non-incidents and examinations were requested for poor performance (10.3 per 1000 races, 95% CI = 9.5-11.1). Horses running in open-class races had greater odds of having an incident than horses in lower-rating classes. The incidence of musculoskeletal injuries (1.3 per 1000 races, 95% CI = 1.13-1.40) and fractures (0.6 per 1000 races, 95% CI = 0.39-0.74) were low and similar to previous New Zealand reports. There was a low incidence of epistaxis (0.8 per 1000 races, 95% CI = 0.69-0.92) possibly due to trainers screening susceptible horses before entering them in races, due to the regulatory consequences of an episode of epistaxis during a race.fals

A Bioeconomic Model for the Thoroughbred Racing Industry-Optimisation of the Production Cycle with a Horse Centric Welfare Perspective

The Thoroughbred racing industry faces new and competing pressures to operate within a modern, changing society. Three major moderators drive the focus and productivity of the industry worldwide: economic sustainability, horse biology and social licence to operate. This review proposes that despite the apparent homogeneity in the structure of racing across jurisdictions due to international regulation of the sport, there are significant differences within each jurisdiction in each of the three moderators. This creates challenges for the comparison of injury risk factors for racehorses within the industry across different jurisdictions. Comparison of the relative distribution of racing and gambling metrics internationally indicates that the Asian jurisdictions have a high focus on gambling efficiency and high economic return of the product, with a high number of starts per horse and the highest relative betting turnover. In contrast, the racing metrics from the USA have proportionally low racing stakes and fewer horses per race. These differences provide insight into the sociology of horse ownership, with a shift from the long-term return on investment held by most jurisdictions to a short-term transitional view and immediate return on investment in others. Wastage studies identify varying risks influenced by the predominant racing culture, training methods, production focus and environment within individual jurisdictions. Increasing societal pressure to maintain high racehorse welfare and reduce the negative impact of gambling poses fluctuating risks to each jurisdiction's social licence to operate. Based on the data presented within this review, the authors propose that the use of a bioeconomic model would permit consideration of all three moderators on industry practice and optimisation of the jurisdiction-specific production cycle with a horse-centric welfare perspective.fals

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal