In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

The response of the Antarctic Circumpolar Current to recent climate change

Observations show a significant intensification of the Southern Hemisphere westerlies, the prevailing winds between the latitudes of 30° and 60° S, over the past decades. A continuation of this intensification trend is projected by climate scenarios for the twenty-first century. The response of the Antarctic Circumpolar Current and the carbon sink in the Southern Ocean to changes in wind stress and surface buoyancy fluxes is under debate. Here we analyse the Argo network of profiling floats and historical oceanographic data to detect coherent hemispheric-scale warming and freshening trends that extend to depths of more than 1,000 m. The warming and freshening is partly related to changes in the properties of the water masses that make up the Antarctic Circumpolar Current, which are consistent with the anthropogenic changes in heat and freshwater fluxes suggested by climate models. However, we detect no increase in the tilt of the surfaces of equal density across the Antarctic Circumpolar Current, in contrast to coarse-resolution model studies. Our results imply that the transport in the Antarctic Circumpolar Current and meridional overturning in the Southern Ocean are insensitive to decadal changes in wind stress

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

<p>Abstract</p> <p>Background</p> <p>Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of the ABC drug transporter proteins P-glycoprotein (Pgp) and Breast cancer resistance protein (BCRP) is a major obstacle for chemotherapy in many tumour types with Pgp conferring particularly poor prognosis in acute myeloid leukaemia (AML). Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin.</p> <p>Methods</p> <p>Effect of barasertib-hQPA on the pHH3 biomarker and cell viability was measured in a panel of leukaemic cell lines and 37 primary AML samples by flow cytometry. Pgp status was determined by flow cytometry and BCRP status by flow cytometry and real-time PCR.</p> <p>Results</p> <p>In this study we report the creation of the cell line OCI-AML3DNR, which over-expresses Pgp but not BCRP or multidrug resistance-associated protein (MRP), through prolonged treatment of OCI-AML3 cells with daunorubicin. We demonstrate that Pgp (OCI-AML3DNR and KG-1a) and BCRP (OCI-AML6.2) expressing AML cell lines are less sensitive to barasertib-hQPA induced pHH3 inhibition and subsequent loss of viability compared to transporter negative cell lines. We also show that barasertib-hQPA resistance in these cell lines can be reversed using known Pgp and BCRP inhibitors. We report that barasertib-hQPA is not an inhibitor of Pgp or BCRP, but by using ¹⁴[C]-barasertib-hQPA that it is effluxed by these transporters. Using phosphoHistone H3 (pHH3) as a biomarker of barasertib-hQPA responsiveness in primary AML blasts we determined that Pgp and BCRP positive primary samples were less sensitive to barasertib-hQPA induced pHH3 inhibition (p = <0.001) than samples without these transporters. However, we demonstrate that IC₅₀inhibition of pHH3 by barasertib-hQPA was achieved in 94.6% of these samples after 1 hour drug treatment, in contrast to the resistance of the cell lines.</p> <p>Conclusion</p> <p>We conclude that Pgp and BCRP status and pHH3 down-regulation in patients treated with barasertib should be monitored in order to establish whether transporter-mediated efflux is sufficient to adversely impact on the efficacy of the agent.</p

Effects of rapid urbanisation on the urban thermal environment between 1990 and 2011 in Dhaka Megacity, Bangladesh

This study investigates the influence of land-use/land-cover (LULC) change on land surface temperature (LST) in Dhaka Megacity, Bangladesh during a period of rapid urbanisation. LST was derived from Landsat 5 TM scenes captured in 1990, 2000 and 2011 and compared to contemporaneous LULC maps. We compared index-based and linear spectral mixture analysis (LSMA) techniques for modelling LST. LSMA derived biophysical parameters corresponded more strongly to LST than those produced using index-based parameters. Results indicated that vegetation and water surfaces had relatively stable LST but it increased by around 2 °C when these surfaces were converted to built-up areas with extensive impervious surfaces. Knowledge of the expected change in LST when one land-cover is converted to another can inform land planners of the potential impact of future changes and urges the development of better management strategies

Discharge pathways and relapse following treatment from early intervention in psychosis services

Background Early intervention in psychosis (EIP) services are the dominant service model in the treatment of first-episode psychosis. They are a time-limited intervention and little is known about discharge destinations and outcomes once EIP treatment has concluded. Aims To understand discharge pathways and predictors of relapse in an EIP service. Method We collected data on all patients with an electronic health record treated by EIP services in Oxford Health NHS Foundation Trust in the UK between 12 January 2006 and 7 March 2017 (n = 701). Our primary outcomes were discharge destination at end of treatment and relapse. Results Most patients (83.5%) were discharged to primary care. Transfer to secondary care was associated with previous in-patient admissions (odds ratio (OR) = 1.92, 95% CI 1.54–2.39) and longer EIP treatment (OR = 1.04, 95% CI 1.03–1.06). Relapse rate was highest shortly after leaving EIP services. Relapse was associated with transfer to secondary care (hazard ratio (HR) = 2.75, 95% CI 1.75–4.31), higher deprivation (HR = 1.03, 95% CI, 1.01–1.05), a substance misuse disorder (HR = 1.81, 95% CI 1.01–3.26) and a comorbid diagnosis of a personality disorder (HR = 2.96, 95% CI 1.39–6.29). Conclusions Most patients treated by the EIP service in Oxfordshire did not receive ongoing mental healthcare from secondary mental health services. We identified high deprivation and those with substance misuse problems or personality disorders as EIP populations with a high risk of relapse