A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, ‘DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m−2 for Group A and 100 mg m−2 for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events

P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.

Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein. Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt. Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface. We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine

The American Astronomical Society, find out more The Institute of Physics, find out more The Sixth Data Release of the Radial Velocity Experiment (Rave). II. Stellar Atmospheric Parameters, Chemical Abundances, and Distances

We present part 2 of the 6th and final Data Release (DR6 or FDR) of the Radial Velocity Experiment (RAVE), a magnitude-limited (9<I<12) spectroscopic survey of Galactic stars randomly selected in the southern hemisphere. The RAVE medium-resolution spectra (R~7500) cover the Ca-triplet region (8410-8795A) and span the complete time frame from the start of RAVE observations on 12 April 2003 to their completion on 4 April 2013. In the second of two publications, we present the data products derived from 518387 observations of 451783 unique stars using a suite of advanced reduction pipelines focussing on stellar atmospheric parameters, in particular purely spectroscopically derived stellar atmospheric parameters (Teff, log(g), and the overall metallicity), enhanced stellar atmospheric parameters inferred via a Bayesian pipeline using Gaia DR2 astrometric priors, and asteroseismically calibrated stellar atmospheric parameters for giant stars based on asteroseismic observations for 699 K2 stars. In addition, we provide abundances of the elements Fe, Al, and Ni, as well as an overall [alpha/Fe] ratio obtained using a new pipeline based on the GAUGUIN optimization method that is able to deal with variable signal-to-noise ratios. The RAVE DR6 catalogs are cross matched with relevant astrometric and photometric catalogs, and are complemented by orbital parameters and effective temperatures based on the infrared flux method. The data can be accessed via the RAVE Web site (http://rave-survey.org) or the Vizier database

The Radial Velocity Experiment (RAVE): Fifth Data Release

Data Release 5 (DR5) of the Radial Velocity Experiment (RAVE) is the fifth data release from a magnitude-limited (9< I < 12) survey of stars randomly selected in the southern hemisphere. The RAVE medium-resolution spectra ($R\sim7500$) covering the Ca-triplet region (8410-8795\AA) span the complete time frame from the start of RAVE observations in 2003 to their completion in 2013. Radial velocities from 520,781 spectra of 457,588 unique stars are presented, of which 255,922 stellar observations have parallaxes and proper motions from the Tycho-Gaia astrometric solution (TGAS) in Gaia DR1. For our main DR5 catalog, stellar parameters (effective temperature, surface gravity, and overall metallicity) are computed using the RAVE DR4 stellar pipeline, but calibrated using recent K2 Campaign 1 seismic gravities and Gaia benchmark stars, as well as results obtained from high-resolution studies. Also included are temperatures from the Infrared Flux Method, and we provide a catalogue of red giant stars in the dereddened color $(J-Ks)_0$ interval (0.50,0.85) for which the gravities were calibrated based only on seismology. Further data products for sub-samples of the RAVE stars include individual abundances for Mg, Al, Si, Ca, Ti, Fe, and Ni, and distances found using isochrones. Each RAVE spectrum is complemented by an error spectrum, which has been used to determine uncertainties on the parameters. The data can be accessed via the RAVE Web site or the Vizier database

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Predicting time-to-failure in rock extrapolated from secondary creep

Stress relaxation experiments are reported that culminate in energetic failure in rocks analogous to the loading cycle and subsequent localization or reactivation on brittle faults embedded in an elastic medium. Universally, rapid primary deformation arrests and transitions into a long secondary deformation phase that ultimately accelerates to catastrophic rupture. Primary deformation (u) conforms to Andrade's law as du/dt similar to (t(c) - t(0))(theta) with a standard exponent of 2/3. In the long, and readily observable, secondary phase, the samples both deform and analogously shed load near linearly in time. This stress relaxation rate exhibits a robust power law dependency with time-to-rupture and exhibits the same 2/3 power law exponent observed in the primary phase. Similarly, the brittle strain energy released in the tertiary collapse scales with a normalized secondary stress relaxation rate. Together, these observations suggest a way to predict both the timing of rupture and its energetics from the observed stress (or strain) rate during the secondary relaxation stage

Measurement properties of the Health Literacy Questionnaire (HLQ) among older adults who present to the emergency department after a fall: A Rasch analysis

Background: Health literacy is an important concept associated with participation in preventive health initiatives, such as falls prevention programs. A comprehensive health literacy measurement tool, appropriate for this population, is required. The aim of this study was to evaluate the measurement properties of the Health Literacy Questionnaire (HLQ) in a cohort of older adults who presented to a hospital emergency department (ED) after a fall. Methods: Older adults who presented to an ED after a fall had their health literacy assessed using the HLQ (n = 433). Data were collected as part of a multi-centre randomised controlled trial of a falls prevention program. Measurement properties of the HLQ were assessed using Rasch analysis. Results: All nine scales of the HLQ were unidimensional, with good internal consistency reliability. No item bias was found for most items (43 of 44). A degree of overall misfit to the Rasch model was evident for six of the nine HLQ scales. The majority of misfit indicated content overlap between some items and does not compromise measurement. A measurement gap was identified for this cohort at mid to high HLQ score. Conclusions: The HLQ demonstrated good measurement properties in a cohort of older adults who presented to an ED after a fall. The summation of the HLQ items within each scale, providing unbiased information on nine separate areas of health literacy, is supported. Clinicians, researchers and policy makers may have confidence using the HLQ scale scores to gain information about health literacy in older people presenting to the ED after a fall. Trial registration: This study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000336684 (27 March 2014)