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SummaryVenous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). We measured df in 87 consecutive patients with newly diagnosed lung cancer prior to treatment and 47 matched-controls. Mean group values were compared for all patients with lung cancer vs controls and for limited disease vs extensive disease. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. Significantly higher values of df were observed in lung cancer patients compared with controls and patients with extensive disease had higher values than those with limited disease (p< 0.05), whilst conventional markers failed to distinguish between these groups. The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot micro-structure and greatest VTE risk.

Linear unselective CCR3 antagonist leads with IC(50) values in the 200 nM range were converted into low nM binding compounds selective at CCR3 by moving the piperidine nitrogen substituent to the carbon at the 2-position of the ring. Substitution of the piperidine nitrogen with simple alkyl and acyl groups was found to improve the selectivity of this new compound class. In particular, N-{3-[(2S, 4R)-1-(propyl)-4-(4-fluorobenzyl)piperidinyl]propyl}-N'-(3-acetylphenyl)urea exhibited single digit nanomolar IC(50) values for CCR3 with >100-fold selectivity against an extensive counter screen panel.

Formative research findings from 10 focus group interviews on botulism are described. Data were collected from a diverse sample of people throughout the United States in 2003, as part of a collaborative multisite initiative sponsored by the Centers for Disease Control and Prevention to improve communications materials on bioterrorism agents. Focus group guides included questions on knowledge, action, emotions, and information seeking in response to a series of scenarios on a hypothetical terrorist attack using botulinum toxin. Data were collected, transcribed, coded, and analyzed using content domains based on risk and health communications theories. Initial participant responses to scenarios were emotional, changing into immediate health and survival concerns conceptualized as information specific to the agent and event. Knowledge about botulism was low, and participants wanted clear, concise, and actionable messages. Broadcast media, the internet, and community-based sources were cited as sources of information. Findings have implications for botulism preparedness messages and for general public risk communications.

The singer-songwriter Renaud, whose work stretches from the mid-1970s to 2003, shows a constant awareness of the genre in which he is working and its place in popular cultural history. This article will concentrate on Renaud’s struggle to come to terms with his own place and status as a chanson artist, and with the place of the chanson artist generally in a commercialised and globalised music industry.Through an examination of his songs and interviews, it will briefly outline Renaud’s relationship with the music industry, exploring how his almost arrogant defiance of the industry, and the mass media generally, changes over his career as he has to come to terms with commercial success. It will explore Renaud’s reasons for the ongoing struggle with the industry and hypothesize that his distaste for commercialism is concomitant with his projection of himself as a chanson artist, which is equated as the binary other of the ‘pop’ or variétés singer. The second part of the article will focus on some of the ways in which Renaud distinguishes himself from more commercial pop singers and draws attention to himself as an auteur.It will argue that although Renaud’s own personal battles with the mass media have perhaps not been as victorious as he may have hoped, the fact that he has inspired a whole new generation of singer-songwriters working in the chanson tradition and looking to ways of mediating the genre’s roots and traditions with today’s more commercial industry, is a testament to Renaud’s own place and importance in chanson history, and reason to view his work as a valid area of academic investigation.

Background: Short courses of oral prednisolone are used as rescue therapy for severe asthma exacerbations. This study compares nebulised budesonide or oral prednisolone, both followed by budesonide Turbohaler®, as a treatment for severe asthma exacerbations, in the absence of life-threatening features. Patients and Methods: Thirteen adults admitted to hospital were randomised to receive either nebulised budesonide (4mg 8-hourly) for 48 to 72 hours followed by budesonide Turbohaler® (1600μg twice daily for 7 days, then 800μg twice daily for 21 days) for 28 days or prednisolone (40mg daily) for 9 to 11 days followed by budesonide Turbohaler® (800μg twice daily) for 21 days. The primary efficacy variable was the change from baseline at 48 hours in forced expiratory volume in 1 second (FEV1). Secondary efficacy variables included an assessment of symptom severity (0 = none, 1 = mild, 2 = moderate, 3 = severe). Results: Difficulties were experienced with patient recruitment in the emergency setting. The results presented are from an incomplete study. Change in FEV1 from baseline to 48 hours was not statistically significantly different between the groups (the study was underpowered to detect a difference in change in FEV1, as the power to detect a prespecified difference between groups was 18%). Nebulised budesonide significantly reduced the severity of wheeze after 24 hours compared with prednisolone [estimate of treatment effect = −0.95; 95% confidence intervals (CI) = −1.76 to −0.15; p = 0.0336 between groups] and 48 hours (estimate of treatment effect = −0.79; 95% CI = −1.42 to −0.15; p = 0.0326 between groups). Conclusion: While oral prednisolone or intravenous hydrocortisone, oxygen and bronchodilators are the mainstay of acute management in severe asthma, the results of this study suggest that nebulised budesonide may assist in regaining control of symptoms during exacerbations of asthma.

Because the phenomenon of dissociation has been difficult to define and disentangle from other constructs, further study of the nature of dissociative experiences and the validity of instruments measuring dissociation was conducted. In this study, multiple measures of dissociative experiences were compared with instruments measuring a variety of theoretically related constructs in a sample of 225 college students. The results supported the convergent validity of the measures of dissociative experiences, but they demonstrated relatively poor discriminant validity. However, poor discriminant validity was not specific to dissociation measures and was found for almost all of the constructs studied. This suggests that dissociation can be seen as a distinct, valid, and reliable phenomenon, and that available instruments measure the phenomenon with similar precision as instruments measuring depression, anxiety, borderline, antisocial, and posttraumatic symptoms.

B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans.

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening illness of unknown aetiology, with no proven pharmacological treatments. There is a limited evidence base indicating that the disease negatively affects quality of life, leading to increased dependence, restrictions on daily activities and fatigue. However, there is a paucity of in-depth information on disease impact across its trajectory, particularly in relation to unmet needs, outcomes of importance to patients and the experiences of carers. Furthermore, little is known about the support and information needs of individuals and their carers, or at what point individual need should trigger a referral to palliative care services. Methods and analysis A mixed-methods study is proposed recruiting individuals with IPF at different stages of the disease and their carers from three respiratory centres in England and Wales. In-depth interviews will be undertaken with participants, adopting an Interpretative Phenomenological Analysis approach. The study will also use validated questionnaires to explore quality of life (EQ-5D), depression (Hospital Anxiety and Depression Scale), breathlessness (Borg dyspnoea scale) and cough (Leicester Cough Questionnaire, Cough Symptom Score). Ethics and dissemination Ethical approvals were gained in April 2012. Palliative care research is a developing field, but there has been limited focus on IPF. We anticipate that the results of the study will enable healthcare professionals to provide appropriate palliative care across the trajectory for individuals with the disease, and their carers, and we therefore aim to disseminate via relevant respiratory and palliative care journals and conferences. We will also support the lay representative involved in the project to disseminate the findings to patient groups.