Glioblastoma in the elderly - how do we choose who to treat?

Objective: Glioblastoma (GBM) is the commonest primary malignant brain tumour amongst the adult population. Incidence peaks in the 7th and 8th decades of life and as our global population ages, rates are increasing. GBM is an almost universally fatal disease with life expectancy in the range of 3–5 months amongst the elderly. Materials and Methods: The assessment of elderly GBM patients prior to treatment decisions is poorly researched and unstandardised. In order to begin tackling this issue we performed a cross-sectional survey across all UK based consultant neuro-oncologists to review their current practice in assessing elderly GBM patients. Results: There were 56 respondents from a total of 93 recipients (60% response rate). All respondents confirmed that at least some patients aged 70 or over were referred to their clinics from the local multidisciplinary team meeting (MDT). Only 18% of consultants routinely performed a cognitive or frailty screening test at initial consultation. Of those who performed a screening test, the majority reported that the results of the test changed their treatment decision in approximately 50% of cases. Participants ranked performance status as the most important factor in determining treatment decisions. Conclusions: Considering the heterogeneity of this patient population, we argue that performance status is a crude measure of vulnerability within this cohort. Elderly GBM patients represent a unique clinical scenario because of the complexity of distinguishing neuro-oncology related symptoms from general frailty. There is a need for specific geriatric assessment models tailored to the elderly neuro-oncology population in order to facilitate treatment decisions

GBTrans: A commensal search for radio pulses with the Green Bank twenty metre telescope

We describe GBTrans, a real-time search system designed to find fast radio bursts (FRBs) using the 20-m radio telescope at the Green Bank Observatory. The telescope has been part of the Skynet educational program since 2015. We give details of the observing system and report on the non-detection of FRBs from a total observing time of 503 days. Single pulses from four known pulsars were detected as part of the commensal observing. The system is sensitive enough to detect approximately half of all currently known FRBs and we estimate that our survey probed redshifts out to about 0.3 corresponding to an effective survey volume of around 124,000~Mpc$^3$. Modeling the FRB rate as a function of fluence, $F$, as a power law with $F^{-\alpha}$, we constrain the index $\alpha < 2.5$ at the 90% confidence level. We discuss the implications of this result in the context of constraints from other FRB surveys.Comment: 7 pages, 6 figure

Astrophysical implications of hypothetical stable TeV-scale black holes

We analyze macroscopic effects of TeV-scale black holes, such as could possibly be produced at the LHC, in what is regarded as an extremely hypothetical scenario in which they are stable and, if trapped inside Earth, begin to accrete matter. We examine a wide variety of TeV-scale gravity scenarios, basing the resulting accretion models on first-principles, basic, and well-tested physical laws. These scenarios fall into two classes, depending on whether accretion could have any macroscopic effect on the Earth at times shorter than the Sun's natural lifetime. We argue that cases with such effect at shorter times than the solar lifetime are ruled out, since in these scenarios black holes produced by cosmic rays impinging on much denser white dwarfs and neutron stars would then catalyze their decay on timescales incompatible with their known lifetimes. We also comment on relevant lifetimes for astronomical objects that capture primordial black holes. In short, this study finds no basis for concerns that TeV-scale black holes from the LHC could pose a risk to Earth on time scales shorter than the Earth's natural lifetime. Indeed, conservative arguments based on detailed calculations and the best-available scientific knowledge, including solid astronomical data, conclude, from multiple perspectives, that there is no risk of any significance whatsoever from such black holes.Comment: Version2: Minor corrections/fixed typos; updated reference

Standards for the diagnosis and management of Complex Regional Pain Syndrome: Results of a European Pain Federation task force

Background: Complex Regional Pain Syndrome is a painful and disabling post-traumatic primary pain disorder. Acute and chronic CRPS are major clinical challenges. In Europe progress is hampered by significant heterogeneity in clinical practice. We sought to establish standards for the diagnosis and management of CPRS. Methods: The European Pain Federation established a pan-European task force of experts in CRPS who followed a four-stage consensus challenge process to produce mandatory quality standards worded as grammatically imperative (must-do) statements. Results: We developed 17 standards in 8 areas of care. There are 2 standards in diagnosis, 1 in multi-disciplinary care, 1 on assessment, 3 for care pathways, 1 on information and education, 4 in pain management, 3 in physical rehabilitation, and 2 on distress management. The standards are presented, summarised, and their generation and consequences discussed. Also presented are domains of practice for which no agreement on a standard could be reached. Areas of research needed to improve the validity and uptake of these standards are discussed. Conclusion: The European Pain Federation task force present 17 standards of the diagnosis and management of CPRS for use in Europe. These are considered achievable for most countries, and aspirational for a minority of countries depending on their healthcare resource and structures.Significance: This position statement summarizes expert opinion on acceptable standards for CRPS care in Europe

Formation of millisecond pulsars with CO white dwarf companions - II. Accretion, spin-up, true ages and comparison to MSPs with He white dwarf companions

Millisecond pulsars (MSPs) are mainly characterised by their spin periods, B-fields and masses - quantities which are largely affected by previous interactions with a companion star in a binary system. In this paper, we investigate the formation mechanism of MSPs by considering the pulsar recycling process in both intermediate-mass X-ray binaries (IMXBs) and low-mass X-ray binaries (LMXBs). The IMXBs mainly lead to the formation of binary MSPs with a massive carbon-oxygen (CO) or an oxygen-neon-magnesium white dwarf (ONeMg WD) companion, whereas the LMXBs form recycled pulsars with a helium white dwarf (He WD) companion. We discuss the accretion physics leading to the spin-up line in the PPdot-diagram and demonstrate that such a line cannot be uniquely defined. We derive a simple expression for the amount of accreted mass needed for any given pulsar to achieve its equilibrium spin and apply this to explain the observed differences of the spin distributions of recycled pulsars with different types of companions. From numerical calculations we present further evidence for significant loss of rotational energy in accreting X-ray MSPs in LMXBs during the Roche-lobe decoupling phase (Tauris 2012) and demonstrate that the same effect is negligible in IMXBs. We examine the recycling of pulsars with CO WD companions via Case BB Roche-lobe overflow (RLO) of naked helium stars in post common envelope binaries. We find that such pulsars typically accrete of the order 0.002-0.007 M_sun which is just about sufficient to explain their observed spin periods. We introduce isochrones of radio MSPs in the PPdot-diagram to follow their spin evolution and discuss their true ages from comparison with observations. Finally, we apply our results of the spin-up process to the massive pulsar J1614-2230 (Paper I) and put new constraints on the birth masses of a number of recycled pulsars. [Abridged]Comment: MNRAS in press, 32 pages, 14 figures, 4 tables, appendix. Version 2: minor typos correcte

Is eastern Mongolia drying? A long-term perspective of a multidecadal trend

Temperatures in semiarid Mongolia have rapidly risen over the past few decades, and increases in drought, urban development, mining, and agriculture have intensified demands on limited water resources. Understanding long-term streamflow variation is critical for Mongolia, particularly if alterations in streamflow are being considered and because of the potential negative impacts of drought on the animal agriculture sector. Here, we present a temporally and spatially improved streamflow reconstruction for the Kherlen River. We have added 11 new records in comparison with two in the original 2001 reconstruction. This new reconstruction extends from 1630 to 2007 and places the most recent droughts in a multicentennial perspective. We find that variations in streamflow have been much greater in the past than in the original study. There was higher variability in the mid to late 1700s, ranging from severe and extended drought conditions from 1723 to 1739 and again in 1768–1778 to two decadal length episodes of very wet conditions in the mid 1700s and late 1700s. Reduced amplitude is seen in the mid-1800s, and several pluvial events are reconstructed for the 1900s. Although recent droughts are severe and disturbing economic and ecological systems in Mongolia and it appears that eastern Mongolia is drying, the drying trend since the late 1900s might in fact be accentuated by a change from a particularly wet era in Mongolia. The recent drought might be a return to more characteristic hydroclimatic conditions of the past four centuries in Mongolia

Walking the creek: reconnecting place through light projection

In this paper, we explore how a light projection sought to convey a range of qualities:conviviality, a sense of place, playfulness, defamiliarisation, and the affective andsensory capacities that were experienced through walking in the distinctive, liminalrealm of Bendigo Creek in Victoria, Australia. The projection aspired to solicit asensory and affective empathy that chimed with the experiences of an earlier eventin which dozens of pedestrians werefilmed walking in the creek. The projectioncontributed to a local campaign to reappraise the much-maligned creek as a localpublic amenity. We discuss the productive potential of solitary and collectivewalking and, subsequently, the attributes of the projection in its static and mobilemanifestation. In so doing, we suggest that publicly engaged, inclusive, creativepractice can offer potent place-making possibilities

Mobility and the city improvement district: Frictions in the human-capital mobile assemblage

In this paper, we interrogate the role of the city improvement district (CID) in the intervention and management of mobility within the context of the South African city and the case study of the Groote Schuur Community Improvement District (GSCID), a public–private urban governance scheme situated in Cape Town’s middle income southern suburbs. Using the theoretical lens of bodily-scale mobility, we investigate the CID’s activation and management. This is useful, as we will demonstrate, because it is through the mobility and immobility at the scale of the body, where the CID’s mandate is operationalised and it is through the control of mobility that the CID’s mission, discourses and activities are linked. This work demonstrates that CIDs, as elite-driven urban renewal initiatives closely aligned with capital interests, employ exclusionary spatial practices that have the potential to shape the twenty-first century urban experience in significant ways. We conclude by theorising the co-constitutive nature of human mobilities and capital as the ‘human-capital mobile assemblage’ and by arguing that the CID occupies an ambivalent place in the contemporary city.IS

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline