Chemistry in the Circumstellar Medium: Unveiling the Dust Formation Zone

The growth of dust grains in the inner regions of late-type stars is shrouded in mystery due to the difficulty of understanding the growth of heterogeneous particles from simple atoms and molecules and the lack of observational data. This article reviews the molecular processes important in circumstellar envelopes and discusses how ALMA might be used to probe the dust formation zone either directly or indirectly.

Delivery of Methylene Blue and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate from cross-linked poly(vinyl alcohol) hydrogels: A potential means of photodynamic therapy of infected wounds

Poly(vinyl alcohol)-borate complexes were evaluated as a potentially novel drug delivery platform suitable for in vivo use in photodynamic antimicrobial chemotherapy (PACT) of wound infections. An optimised formulation (8.0%w/w PVA, 2.0% w/w borax) was loaded with 1.0 mg ml(-1) of the photosensitisers Methylene Blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Both drugs were released to yield receiver compartment concentrations (>5.0 mu g ml(-1)) found to be phototoxic to both planktonic and bicifilm-grown methicillin-resistant Staphylococcus aureus (MRSA), a common cause of wound infections in hospitals. Newborn calf serum, used to simulate the conditions prevalent in an exuding wound, did not adversely affect the properties of the hydrogels and had no significant effect on the rate of TMP-mediated photodynamic kill of MRSA, despite appreciably reducing the fluence rate of incident light. However, MB-mediated photodynamic kill of MRSA was significantly reduced in the presence of calf serum and when the clinical isolate was grown in a biofilm. Results support the contention that delivery of MB or TMP using gel-type vehicles as part of PACT could make a contribution to the photodynamic eradication of MRSA from infected wounds. (C) 2009 Elsevier B.V. All rights reserved.

Dynamic Buffer Management for Multimedia Services in Beyond 3G Wireless Networks

This paper investigates a dynamic buffer man-agement scheme for QoS control of multimedia services in be-yond 3G wireless systems. The scheme is studied in the context of the state-of-the-art 3.5G system i.e. the High Speed Downlink Packet Access (HSDPA) which enhances 3G UMTS to support high-speed packet switched services. Unlike earlier systems, UMTS-evolved systems from HSDPA and beyond incorporate mechanisms such as packet scheduling and HARQ in the base station necessitating data buffering at the air interface. This introduces a potential bottleneck to end-to-end communication. Hence, buffer management at the air interface is crucial for end-to-end QoS support of multimedia services with multi-plexed parallel diverse flows such as video and data in the same end-user session. The dynamic buffer management scheme for HSDPA multimedia sessions with aggregated real-time and non real-time flows is investigated via extensive HSDPA simulations. The impact of the scheme on end-to-end traffic performance is evaluated with an example multimedia session comprising a real-time streaming flow concurrent with TCP-based non real-time flow. Results demonstrate that the scheme can guar-antee the end-to-end QoS of the real-time streaming flow, whilst simultaneously protecting the non real-time flow from starva-tion resulting in improved end-to-end throughput performance

The Effectiveness of Weight Management Interventions in Breastfeeding Women—A Systematic Review and Critical Evaluation

Background: The postpartum period is a vulnerable time for excess weight retention, particularly for the increasing number of women who are overweight at the start of their pregnancy and subsequently find it difficult to lose additional weight gained during pregnancy. Although postpartum weight management interventions play an important role in breaking this potentially vicious cycle of weight gain, the effectiveness of such interventions in breastfeeding women remains unclear. Our aim was to systematically review the literature about the effectiveness of weight management interventions in breastfeeding women.

Methods: Seven electronic databases were searched for eligible papers. Intervention studies included were carried out exclusively in breastfeeding mothers, ≤2 years postpartum and with a body mass index greater than 18.5 kg/m2, with an outcome measure of change in weight and/or body composition.

Results: Six studies met the selection criteria, and were stratified according to the type of intervention and outcome measures. Despite considerable heterogeneity among studies, the dietary-based intervention studies appeared to be the most efficacious in promoting weight loss; however, few studies were tailored toward the needs of breastfeeding women.

Conclusions: Weight management interventions which include an energy-restricted diet may play a key role in successful postpartum weight loss for breastfeeding mothers.

The EU Charter of Fundamental Rights in the case law of the European Court of Human Rights

The European Court of Human Rights has begun to refer to the EU Charter of Fundamental Rights in order to support its reasoning for interpreting the European Convention on Human Rights in a particular way. But the EU Charter does not yet have any special status in that regard, being treated by the Court as on a par with numerous other documents of international law. The Court’s use of the Charter began in connection with arts 8 and 12 of the Convention (the right to a family life and the right to marry) but in subsequent years it has been extended to many other Articles of the Convention. It is in relation to art.6 (the right to a fair trial) that the Charter’s influence has been most noticeable so far, the Court having changed its position on two important aspects of Article 6 partly because of the wording of the EU Charter. But the influence on art.3 (in relation to the rights of asylum seekers), art.7 (in relation to retroactive penal laws), art.9 (in relation to the right to conscientious objection) and art.11 (in relation to rights of trades unions) has also been significant. The potential for the Charter to have greater influence on the Court’s jurisprudence in years to come remains considerable.

Treatment of retinopathy of prematurity in Northern Ireland, 2000-2011: a population-based study

Purpose To evaluate the incidence of treatment-requiring retinopathy of prematurity (ROP) over a 12-year-period in Northern Ireland. Methods The medical records of all infants treated for ROP from January 2000 to December 2011were retrospectively reviewed and cross-referenced with the Neonatal Intensive Care Outcomes Research and Evaluation (NICORE) database. Results The Northern Ireland population data showed an increase in the number of live births from 2000 to 2011. The proportion of babies born with a birth weight <1501 g and/or <32 weeks’ gestational age remained constant (χ2 trend = 3.220, P = 0.0727), although the proportion of these babies who died prior to 42 weeks’ gestation decreased from 2000 to 2011 (P = 0.0196 using χ2 for trend = 5.445; P = 0.0354 using χ2 = 20.809). The prevalence of treatment-requiring ROP in these infants increased from 1.05% in 2000 to 5.78% in 2011 (P < 0.001 using χ2 trend = 16.309; P < 0.001 using χ2 = 31.378). Conclusions The present population-based study highlights that the incidence of treatment- requiring ROP is increasing in Northern Ireland. The increasing number of infants requiring treatment will need to be taken into consideration in the commissioning process for ROP services in Northern Ireland.

Empowering Art: Reconfiguring narratives of trauma and hope in the Australian national imaginary

Aboriginal art has been the source of much contention between art curators, gallery owners, art critics and Aboriginal artists themselves. Early aesthetic debates about whether so-called traditional works should be considered ethnographic or artistic have led, at times, to conflicts over the rights of Aboriginal people to have their works exhibited according to the criteria applied to other kinds of Western artworks. This article explores how the dilemmas of troubled ethno-histories are critically embodied and reconfigured in texture and colour. It considers the problems that silenced histories pose for those responsible for their display to the public. As Aboriginal images often conceal troubled intercultural encounters it asks how artworks can be used to provide a counter-polemic to national rhetoric as artists seek to reshape and improve intergenerational futures. This text is published as a counterpart to the contribution to Disturbing Pasts from the artist Heather Kamarra Shearer.

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial

Background: Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. 

Methods: In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. 

Findings: Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3-4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3-4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3-4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. 

Interpretation: Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. 

Funding: Algeta ASA and Bayer HealthCare Pharmaceuticals.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial

BACKGROUND: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases.

METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751.

FINDINGS: Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5-18·0] vs 9·8 months [7·3-23·7]; hazard ratio [HR]=0·66, 95% CI 0·52-0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53-0·85) and spinal cord compression (HR=0·52, 95% CI 0·29-0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35-1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28-1·82).

INTERPRETATION: Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.

FUNDING: Algeta and Bayer HealthCare Pharmaceuticals.

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.

Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.

Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally.

Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.

Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.

Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39–0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85,p = 0.002). Adverse event incidences were similar between opioid subgroups.

Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.

Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.