The clinical significance of the FUS-CREB3L2 translocation in low-grade fibromyxoid sarcoma

<p>Abstract</p> <p>Background</p> <p>Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue neoplasm with a deceptively benign histological appearance. Local recurrences and metastases can manifest many years following excision. The <it>FUS-CREB3L2 </it>gene translocation, which occurs commonly in LGFMS, may be detected by reverse-transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridisation (FISH). We assessed the relationship between clinical outcome and translocation test result by both methods.</p> <p>Methods</p> <p>We report genetic analysis of 23 LGFMS cases and clinical outcomes of 18 patients with mean age of 40.6 years. During follow-up (mean 24.8 months), there were no cases of local recurrence or metastasis. One case was referred with a third recurrence of a para-spinal tumour previously incorrectly diagnosed as a neurofibroma.</p> <p>Results</p> <p>Results showed 50% of cases tested positive for the <it>FUS-CREB3L2 </it>translocation by RT-PCR and 81.8% by FISH, suggesting FISH is more sensitive than RT-PCR for confirming LGFMS diagnosis. Patients testing positive by both methods tended to be younger and had larger tumours. Despite this, there was no difference in clinical outcome seen during short and medium-term follow-up.</p> <p>Conclusions</p> <p>RT-PCR and FISH for the <it>FUS-CREB3L2 </it>fusion transcript are useful tools for confirming LGFMS diagnosis, but have no role in predicting medium-term clinical outcome. Due to the propensity for late recurrence or metastasis, wide excision is essential, and longer-term follow-up is required. This may identify a difference in long-term clinical outcome between translocation-positive and negative patients.</p

A saposin-lipoprotein nanoparticle system for membrane proteins.

A limiting factor in membrane protein research is the ability to solubilize and stabilize such proteins. Detergents are used most often for solubilizing membrane proteins, but they are associated with protein instability and poor compatibility with structural and biophysical studies. Here we present a saposin-lipoprotein nanoparticle system, Salipro, which allows for the reconstitution of membrane proteins in a lipid environment that is stabilized by a scaffold of saposin proteins. We demonstrate the applicability of the method on two purified membrane protein complexes as well as by the direct solubilization and nanoparticle incorporation of a viral membrane protein complex from the virus membrane. Our approach facilitated high-resolution structural studies of the bacterial peptide transporter PeptTSo2 by single-particle cryo-electron microscopy (cryo-EM) and allowed us to stabilize the HIV envelope glycoprotein in a functional state

Accountability and Transparency of Entrepreneurial Journalism: Unresolved ethical issues in crowdfunded journalism projects

Crowdfunding is a new business model in which journalists rely—and depend—on (micro-) payments by a large number of supporters to finance their reporting. In this form of entrepreneurial journalism the roles of publisher, fundraiser and journalist often overlap. This raises questions about conflicts of interest, accountability and transparency. The article presents the results of selected case studies in four different European countries—Germany (Krautreporter), Italy (Occhidellaguerra), the United Kingdom (Contributoria) and the Netherlands (De Correspondent)—as well as one US example (Kickstarter). The study used a two-step methodological approach: first a content analysis of the websites and the Twitter accounts with regard to practices of media accountability, transparency and user participation was undertaken. The aim was to investigate how far ethical challenges in crowdfunded entrepreneurial journalism are accounted for. Second, we present findings from semi-structured interviews with journalists from each crowdfunding. The study provides evidence about the ethical issues in this area, particularly in relation to production transparency and responsiveness. The study also shows that in some cases of crowdfunding (platforms), accountability is outsourced and implemented only through the audience participation

Neutral Hydrogen and Optical Observations of Edge-on Galaxies: Hunting for Warps

We present 21-cm HI line and optical R-band observations for a sample of 26 edge-on galaxies. The HI observations were obtained with the Westerbork Synthesis Radio Telescope, and are part of the WHISP database (Westerbork HI Survey of Spiral and Irregular Galaxies). We present HI maps, optical images, and radial HI density profiles. We have also derived the rotation curves and studied the warping and lopsidedness of the HI disks. 20 out of the 26 galaxies of our sample are warped, confirming that warping of the HI disks is a very common phenomenon in disk galaxies. Indeed, we find that all galaxies that have an extended HI disk with respect to the optical are warped. The warping usually starts around the edge of the optical disk. The degree of warping varies considerably from galaxy to galaxy. Furthermore, many warps are asymmetric, as they show up in only one side of the disk or exhibit large differences in amplitude in the approaching and receding sides of the galaxy. These asymmetries are more pronounced in rich environments, which may indicate that tidal interactions are a source of warp asymmetry. A rich environment tends to produce larger warps as well. The presence of lopsidedness seems to be related to the presence of nearby companions.Comment: To appear in Astronomy & Astrophysic

A parallel group randomised open blinded evaluation of Acceptance and Commitment Therapy for depression after psychosis: Pilot trial outcomes (ADAPT)

BACKGROUND: Depression is one of the major contributors to poorer quality of life amongst individuals with psychosis and schizophrenia. The study was designed as a Pilot Trial to determine the parameters of a larger, definitive pragmatic multi-centre randomised controlled trial of Acceptance and Commitment Therapy for depression after psychosis (ACTdp) for individuals with a diagnosis of schizophrenia who also meet diagnostic criteria for major depression. METHODS: Participants were required to meet criteria for schizophrenia and major depression. Blinded follow-ups were undertaken at 5-months (end of treatment) and at 10-months (5-months posttreatment). Primary outcomes were depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck Depression Inventory (BDI). RESULTS: A total of 29 participants were randomised to ACTdp + Standard Care (SC) (n=15) or SC alone (n=14). We did not observe significant differences between groups on the CDSS total score at 5-months (Coeff=-1.43, 95%CI -5.17, 2.32, p=0.45) or at 10-months (Coeff=1.8, 95%CI -2.10, 5.69, p=0.36). In terms of BDI, we noted a statistically significant effect in favour of ACTdp+SC at 5-months (Coeff=-8.38, 95%CI -15.49, -1.27, p=0.02) but not at 10-months (Coeff=-4.85, 95%CI -12.10, 2.39, p=0.18). We also observed significant effects on psychological flexibility at 5-months (Coeff=-8.83, 95%CI -14.94, -2.71, p&lt;0.01) but not 10-months (Coeff=-4.92, 95%CI -11.09, 1.25, p=0.11). IMPLICATIONS: In this first RCT of a psychological therapy with depression as the primary outcome, ACT is a promising intervention for depression in the context of psychosis. A further large-scale definitive randomised controlled trial is required to determine effectiveness. TRIAL REGISTRATION: ISRCTN: 33306437

Determinants of adults' intention to vaccinate against pandemic swine flu

This article has been made available through the Brunel Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Background: Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods: Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results: The extended Theory of Planned Behaviour predicted 60% of adults’ intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: “I cannot be bothered to get a swine flu vaccination” and two perceived benefits: “vaccination decreases my chance of getting swine flu or its complications” and “if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor,” being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions: Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.This article is available through the Brunel Open Access Publishing Fund

Modelling the Health Impact of an English Sugary Drinks Duty at National and Local Levels

Increasing evidence associates excess refined sugar intakes with obesity, Type 2 diabetes and heart disease. Worryingly, the estimated volume of sugary drinks purchased in the UK has more than doubled between 1975 and 2007, from 510ml to 1140ml per person per week. We aimed to estimate the potential impact of a duty on sugar sweetened beverages (SSBs) at a local level in England, hypothesising that a duty could reduce obesity and related diseases. Methods and Findings We modelled the potential impact of a 20% sugary drinks duty on local authorities in England between 2010 and 2030. We synthesised data obtained from the British National Diet and Nutrition Survey (NDNS), drinks manufacturers, Office for National Statistics, and from previous studies. This produced a modelled population of 41 million adults in 326 lower tier local authorities in England. This analysis suggests that a 20% SSB duty could result in approximately 2,400 fewer diabetes cases, 1,700 fewer stroke and coronary heart disease cases, 400 fewer cancer cases, and gain some 41,000 Quality Adjusted Life Years (QALYs) per year across England. The duty might have the biggest impact in urban areas with young populations. Conclusions This study adds to the growing body of evidence suggesting health benefits for a duty on sugary drinks. It might also usefully provide results at an area level to inform local price interventions in England

New insights from old bones: DNA preservation and degradation in permafrost preserved mammoth remains

Despite being plagued by heavily degraded DNA in palaeontological remains, most studies addressing the state of DNA degradation have been limited to types of damage which do not pose a hindrance to Taq polymerase during PCR. Application of serial qPCR to the two fractions obtained during extraction (demineralization and protein digest) from six permafrost mammoth bones and one partially degraded modern elephant bone has enabled further insight into the changes which endogenous DNA is subjected to during diagenesis. We show here that both fractions exhibit individual qualities in terms of the prevailing type of DNA (i.e. mitochondrial versus nuclear DNA) as well as the extent of damage, and in addition observed a highly variable ratio of mitochondrial to nuclear DNA among the six mammoth samples. While there is evidence suggesting that mitochondrial DNA is better preserved than nuclear DNA in ancient permafrost samples, we find the initial DNA concentration in the bone tissue to be as relevant for the total accessible mitochondrial DNA as the extent of DNA degradation post-mortem. We also evaluate the general applicability of indirect measures of preservation such as amino-acid racemization, bone crystallinity index and thermal age to these exceptionally well-preserved samples