A synchrotron self-Compton model with low energy electron cut-off for the blazar S5 0716+714

Rapid inverse Compton cooling sets in when the brightness temperature (T_B) of a self-absorbed synchrotron source with power-law electrons reaches ~10^{12} K. However, T_B inferred from observations of intra-day variable sources (IDV) are well above the "Compton catastrophe" limit. This can be understood if the underlying electron distribution cuts off at low energy. We approximate a low-energy cut-off with monoenergetic electrons. We compute the synchrotron self-Compton (SSC) spectrum of such distribution, and using the IDV source S5~0716+714 as an example, we compare it to the observed SED of S5~0716+714. The hard radio spectrum is well-fitted by this model, and the optical data can be accommodated by a power-law extension to the electron spectrum. We therefore examine the scenario of an injection of electrons that is a double power law in energy with a hard low-energy component that does not contribute to the synchrotron opacity. We show that the double power-law injection model is in good agreement with the observed SED of S5~0716+714. For intrinsic variability, we find that a Doppler factor of D\geq30 can explain the observed SED provided that low-frequency (<32 GHz) emission originates from a larger region than the higher-frequency emission. To fit the entire spectrum, D\geq65 is needed. We find the constraint imposed by induced Compton scattering at high T_B is insignificant in our model. We confirm that electron distribution with a low-energy cut-off can explain the high T_B in compact radio sources. We show that synchrotron spectrum from such distributions naturally accounts for the observed hard radio continuum with a softer optical component, without the need for an inhomogeneous source.Comment: 13 pages, 5 figures, 1 table, to appear in A&A; refereces removed from caption of Fig.3, added acknowledgemen

Oxycodone for cancer‐related pain

Background: Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain. Objectives: To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search. Selection criteria: We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults. Data collection and analysis: Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach. Main results: We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events. Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings. The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety. Authors' conclusions: Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain

Yoga for depression: the research evidence

Background: Yoga-based interventions may prove to be an attractive option for the treatment of depression. The aim of this study is to systematically review the research evidence on the effectiveness of yoga for this indication Methods: Searches of the major biomedical databases including MEDLINE, EMBASE, ClNAHL, PsycINFO and the Cochrane Library were conducted. Specialist complementary and alternative medicine (CAM) and the IndMED databases were also searched and efforts made to identify unpublished and ongoing research. Searches were conducted between January and June 2004. Relevant research was categorised by study type and appraised. Clinical commentaries were obtained for studies reporting clinical outcomes. Results: Five randomised controlled trials were located, each of which utilised different forms of yoga interventions and in which the severity of the condition ranged from mild to severe. All trials reported positive findings but methodological details such as method of randomisation, compliance and attrition rates were missing. No adverse effects were reported with the exception of fatigue and breathlessness in participants in one study. Limitations: No language restrictions were imposed on the searches conducted but no searches of databases in languages other than English were included. Conclusions: Overall, the initial indications are of potentially beneficial effects of yoga interventions on depressive disorders. Variation in interventions, severity and reporting of trial methodology suggests that the findings must be interpreted with caution. Several of the interventions may not be feasible in those with reduced or impaired mobility. Nevertheless, further investigation of yoga as a therapeutic intervention is warranted

Matrix Metalloproteinase-1 and -9 in Human Placenta during Spontaneous Vaginal Delivery and Caesarean Sectioning in Preterm Pregnancy

Preterm birth is a major public health problem in terms of loss of life, long-term and short term disabilities worldwide. The process of parturition (both term and preterm) involves intensive remodelling of the extracellular matrix (ECM) in the placenta and fetal membranes by matrix metalloproteinases (MMPs). Our previous studies show reduced docosahexaenoic acid (DHA) in women delivering preterm. Further omega 3 fatty acids are reported to regulate MMP levels. This study was undertaken to examine the placental levels of MMPs and their association with placental DHA levels in women delivering preterm. The levels of MMP-1 and MMP-9 in 74 women delivering preterm (52 by spontaneous vaginal delivery and 22 by caesarean sectioning) and 75 women delivering at term (59 by spontaneous vaginal delivery and 16 by caesarean sectioning) were determined by enzyme-linked immunosorbent assay (ELISA) and their association with placental DHA was studied. Placental MMP-1 levels were higher (p<0.05) in women delivering preterm (both by spontaneous vaginal delivery and caesarean sectioning) as compared to those delivering at term. In contrast, placental MMP-9 levels in preterm pregnancies was higher (p<0.05) in women with spontaneous vaginal delivery while lower (p<0.05) in women delivering by caesarean sectioning. Low placental DHA was associated with higher placental MMP-9 levels. Our study suggests a differential effect of mode of delivery on the levels of MMPs from placenta. Further this study suggests a negative association of DHA and the levels of MMP-9 in human placenta although the mechanisms need further study

DASMI: exchanging, annotating and assessing molecular interaction data

Motivation: Ever increasing amounts of biological interaction data are being accumulated worldwide, but they are currently not readily accessible to the biologist at a single site. New techniques are required for retrieving, sharing and presenting data spread over the Internet

A Practice Guide for Continuous Opioid Therapy for Refractory Daily Headache: Patient Selection, Physician Requirements, and Treatment Monitoring

( Headache 2010;50:1175-1193)To provide a guide to the use and limitations of continuous opioid therapy (COT, or daily scheduled opioids) for refractory daily headache, based on the best available evidence and expert clinical experience.There has been a dramatic increase in opioid administration over the past 25 years, with limited evidence of efficacy for either pain reduction or increased function, and increasing evidence of adverse effects, including headache chronification. To date, there has been no consensus on headache-specific guidelines for selecting patients for COT, physician requirements, and treatment monitoring.A multidisciplinary committee of physicians and allied health professionals with extensive experience and expertise in the administration of opioids to headache patients, undertook a review of the available evidence from the research and clinical literature (using the PubMed database for articles through December 2009) to develop headache-specific treatment recommendations. This guide reflects the opinions of its authors and is not an official document of the American Headache Society.The guide identifies factors that would qualify or disqualify the use of COT, including, determination of intractability prior to initiating COT, requisite experience of the prescriber, and requirements for a formal monitoring system to assess appropriate use, safety, efficacy, and functional impact. An appendix reviews the available evidence for efficacy of COT in chronic headache and noncancer pain, paradoxical effects (opioid-induced hyperalgesia, medication overuse headache, opioid-related reduction in triptan and nonsteroidal anti-inflammatory drug efficacy), other adverse effects (nausea and constipation, insomnia and sleep apnea, respiratory depression and sudden cardiac death, reductions in sex hormones, issues during pregnancy, neurocognitive functioning), and issues related to comorbid psychiatric disorders.Only a select and very limited group (estimate of 10-20%) of refractory headache patients who meet criteria for COT respond with convincing headache reduction and functional improvement over the long-term. Conservative and empirically based guidelines will help identify those patients for whom a COT trial may be appropriate, while protecting their welfare and safety.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79211/1/j.1526-4610.2010.01733.x.pd

Individual recovery expectations and prognosis of outcomes in non‐specific low back pain:prognostic factor review

BACKGROUND: Low back pain is costly and disabling. Prognostic factor evidence can help healthcare providers and patients understand likely prognosis, inform the development of prediction models to identify subgroups, and may inform new treatment strategies. Recent studies have suggested that people who have poor expectations for recovery experience more back pain disability, but study results have differed. OBJECTIVES: To synthesise evidence on the association between recovery expectations and disability outcomes in adults with low back pain, and explore sources of heterogeneity. SEARCH METHODS: The search strategy included broad and focused electronic searches of MEDLINE, Embase, CINAHL, and PsycINFO to 12 March 2019, reference list searches of relevant reviews and included studies, and citation searches of relevant expectation measurement tools. SELECTION CRITERIA: We included low back pain prognosis studies from any setting assessing general, self-efficacy, and treatment expectations (measured dichotomously and continuously on a 0 - 10 scale), and their association with work participation, clinically important recovery, functional limitations, or pain intensity outcomes at short (3 months), medium (6 months), long (12 months), and very long (> 16 months) follow-up. DATA COLLECTION AND ANALYSIS: We extracted study characteristics and all reported estimates of unadjusted and adjusted associations between expectations and related outcomes. Two review authors independently assessed risks of bias using the Quality in Prognosis Studies (QUIPS) tool. We conducted narrative syntheses and meta-analyses when appropriate unadjusted or adjusted estimates were available. Two review authors independently graded and reported the overall quality of evidence. MAIN RESULTS: We screened 4635 unique citations to include 60 studies (30,530 participants). Thirty-five studies were conducted in Europe, 21 in North America, and four in Australia. Study populations were mostly chronic (37%), from healthcare (62%) or occupational settings (26%). General expectation was the most common type of recovery expectation measured (70%); 16 studies measured more than one type of expectation. Usable data for syntheses were available for 52 studies (87% of studies; 28,885 participants). We found moderate-quality evidence that positive recovery expectations are strongly associated with better work participation (narrative synthesis: 21 studies; meta-analysis: 12 studies, 4777 participants: odds ratio (OR) 2.43, 95% confidence interval (CI) 1.64 to 3.62), and low-quality evidence for clinically important recovery outcomes (narrative synthesis: 12 studies; meta-analysis: 5 studies, 1820 participants: OR 1.89, 95% CI 1.49 to 2.41), both at follow-up times closest to 12 months, using adjusted data. The association of recovery expectations with other outcomes of interest, including functional limitations (narrative synthesis: 10 studies; meta-analysis: 3 studies, 1435 participants: OR 1.40, 95% CI 0.85 to 2.31) and pain intensity (narrative synthesis: 9 studies; meta-analysis: 3 studies, 1555 participants: OR 1.15, 95% CI 1.08 to 1.23) outcomes at follow-up times closest to 12 months using adjusted data, is less certain, achieving very low- and low-quality evidence, respectively. No studies reported statistically significant or clinically important negative associations between recovery expectations and any low back pain outcome. AUTHORS' CONCLUSIONS: We found that individual recovery expectations are probably strongly associated with future work participation (moderate-quality evidence) and may be associated with clinically important recovery outcomes (low-quality evidence). The association of recovery expectations with other outcomes of interest is less certain. Our findings suggest that recovery expectations should be considered in future studies, to improve prognosis and management of low back pain

Psychosocial Risk Factors in Disordered Gambling: A Descriptive Systematic Overview of Vulnerable Populations

Background: Gambling is a behaviour engaged in by millions of people worldwide; for some, gambling can become a severely maladaptive behaviour, and previous research has identified a wide range of psychosocial risk factors that can be considered important for the development and maintenance of disordered gambling. Although risk factors have been identified, the homogeneity of risk factors across specific groups thought to be vulnerable to disordered gambling is to date, unexplored. Methods: To address this, the current review sought to conduct a systematic overview of literature relating to seven vulnerable groups: young people and adolescents, older adults, women, veterans, indigenous peoples, prisoners, and low socio-economic/income groups. Results: Multiple risk factors associated with disordered gambling were identified; some appeared consistently across most groups, including being male, co-morbid mental and physical health conditions, substance use disorders, accessibility and availability of gambling, form and mode of gambling, and experience of trauma. Further risk factors were identified that were specific to each vulnerable group. Conclusion: Within the general population, certain groups are more vulnerable to disordered gambling. Although some risk factors are consistent across groups, some risk factors appear to be group specific. It is clear that there is no homogenous pathway in to disordered gambling, and that social, developmental, environmental and demographic characteristics can all interact to influence an individual’s relationship with gambling