Capsaicinoids – a potential role for weight management

The prevalence of overweight and obese individuals has risen dramatically in populations around the world over the last 30 years (Popkin et al., 2012) representing a rapidly growing burden to public health services (Wang et al., 2011). Reliance on lifestyle modification, although initially promising, has proven to be unsuccessful over the longer term (Barte et al., 2010) and there are currently a lack of successful treatment options. Capsaicinoids are a bio-active group of compounds, naturally occurring in the fruit of the plant from the genus capsicum. Initial research suggests these compounds may have beneficial effects on weight loss outcomes when ingested (Lejeune et al., 2003). A systematic review of the available literature on capsaicinoids found evidence that ingestion may increase energy expenditure by around 210kJ/day and lipid oxidation by around 20%. Ingestion may also reduce energy intake although evidence has been conflicting and the size of the effect unclear. To further aid understanding, a meta-analysis was undertaken involving intervention trials assessing the effects of capsaicinoids on energy intake. Analysis suggested capsaicinoid ingestion prior to a meal reduced ad libitum energy intake energy intake by 251kJ (60kcal) per meal (95% confidence interval of 337 – 166kJ) p < 0.001. Caution should be applied to this result however, due to the small size of the reduction and the short term nature of the trials involved. Longer term trials are needed to assess potential changes in body composition as a result of capsaicinoid interventions. To this end, a six-week placebo control intervention study was conducted to assess changes in body fat in 60 Caucasian women. Results of a sensitivity analysis found a small, statistically significant decrease in body fat percentage (0.64%, p = 0.022) and total body fat (0.67kg, p = 0.007) in the intervention group. However, the robustness of these findings are called into question by the results of an interaction analysis which of observed no significant difference between placebo control and intervention groups over time for these outcomes. The effect was also small and therefore longer term supplementation would be required to produce a medically beneficial changes in body composition

A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors

BACKGROUND: Patients with DLBCL who are ineligible for or have relapsed after aggressive salvage chemotherapy have a poor prognosis. CD40 is expressed on multiple B-cell neoplasms including DLBCL and is a potential target for immunotherapy. Dacetuzumab (SGN-40), a non-blocking, partial agonist, humanized IgG1, anti-CD40 monoclonal antibody, has previously demonstrated anti-lymphoma activity in a phase I study. METHODS: A phase II study was undertaken to evaluate the rate and duration of objective responses and safety of single-agent dacetuzumab in relapsed DLBCL. Forty-six adult patients with relapsed/refractory DLBCL received up to 12 cycles of intravenous dacetuzumab using intrapatient dose-escalation to a target dose of 8 mg/kg/week in an initial 5-week cycle, followed by 4-week cycles of 8 mg/kg/week. Study endpoints included rate and duration of objective responses, safety, survival, pharmacokinetics, immunogenicity, and exploratory correlative studies. RESULTS: Overall response rate was 9% and disease control rate (complete remission + partial remission + stable disease) was 37%. Common non-hematologic adverse events (AEs) included fatigue, headache, chills, fever, and nausea. The most frequent Grade 3–4 non-hematologic AE was deep venous thrombosis (3 patients). Grade 3–4 lymphopenia (41%), neutropenia (13%), or thrombocytopenia (19%) occurred without associated infection or bleeding. Reversible ocular events, including conjunctivitis and ocular hyperemia, occurred in 8 patients (17%). Patient-specific factors, including Fc-gamma-RIIIa polymorphism, did not appear to correlate with antitumor activity. CONCLUSIONS: Single-agent dacetuzumab has modest activity and manageable toxicity in unselected patients with relapsed DLBCL. Combination regimens and robust methods of patient selection may be necessary for further development. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00435916

The FLASH pilot survey: an HI absorption search against MRC 1-Jy radio sources

We report an ASKAP search for associated HI 21-cm absorption against bright radio sources from the Molonglo Reference Catalogue (MRC) 1-Jy sample. The search uses pilot survey data from the ASKAP First Large Absorption Survey in \hi (FLASH) covering the redshift range $0.42 < z < 1.00$. From a sample of 62 MRC 1-Jy radio galaxies and quasars in this redshift range we report three new detections of associated HI 21-cm absorption, yielding an overall detection fraction of $1.8\%^{+4.0\%}_{-1.5\%}$. The detected systems comprise two radio galaxies (MRC 2216$-$281 at $z=0.657$ and MRC 0531$-$237 at $z=0.851$) and one quasar (MRC 2156$-$245 at $z=0.862$). The MRC 0531$-$237 absorption system is the strongest found to date, with a velocity integrated optical depth of $\rm 143.8 \pm 0.4 \ km \ s^{-1}$. All three objects with detected HI 21-cm absorption are peaked-spectrum or compact steep-spectrum (CSS) radio sources, classified based on our SED fits to the spectra. Two of them show strong interplanetary scintillation at 162 MHz, implying that the radio continuum source is smaller than 1 arcsec in size even at low frequencies. Among the class of peaked-spectrum and compact steep-spectrum radio sources, the HI detection fraction is $23\%^{+22\%}_{-13\%}$. This is consistent within $1\sigma$ with a detection fraction of $\approx 42\%^{+21\%}_{-15\%}$ in earlier reported GPS and CSS samples at intermediate redshifts ($0.4 < z < 1.0$). All three detections have a high 1.4 GHz radio luminosity, with MRC 0531$-$237 and MRC 2216$-$281 having the highest values in the sample, $\rm > 27.5 \ W \ Hz^{-1}$. The preponderance of extended radio sources in our sample could partially explain the overall low detection fraction, while the effects of a redshift evolution in gas properties and AGN UV luminosity on the neutral gas absorption still need to be investigated.Comment: 28 pages, 9 figures and 7 Tables. Submitted to MNRA

Confrontational Behavior and Escalation to War 1816-1980: A Research Plan

The understanding of international war, like many complex social events, may be - and has been - ap proached from a range of theoretical perspectives and via a variety of research strategies. Outside of the work of Bloch (1898), Sorokin (1936), Richardson (1941), and Wright (1942), however, there was little re search of a scientific nature until the mid-1960s. And while these past fifteen years have certainly not given us a compelling theory of international war, they have seen a steady growth in cumulative knowledge regar ding the correlates of war. These results, despite the expected mix of inconsistencies and anomalies, provide us with some sense of the factors that are most consistently associated with war over the last century and a half, along with some tentative insights into the rising and declining potency of these factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68556/2/10.1177_002234338201900104.pd

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]