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Bert De Munck, Anne Winter (eds.), Gated Communities? Regulating Migration in Early Modern Cities (2012), xiv + 294 (Ashgate, Farnham), 78 £
No full textScreening multi-reservoir system designs via efficient trade-offs - informing infrastructure investment decisions on the Blue Nile
No full textDirect control of EV charging on feeders with EV clusters
No full text(paper accepted) The My Electric Avenue project has established ten clusters of electric vehicle (EV) users on real UK feeders, and is currently running trials that explore EV user behaviours and the impact of charging vehicles on local networks. As part of the trials, the technology Esprit has been deployed to curtail EV charging during high feeder loads using Power Line Carrier (PLC) communication, to assess its capability to delay or prevent the need for network reinforcements whilst accommodating the needs and perceptions of EV users. With over 200 EVs in the field, this paper provides an overview of the trials and the technical and social data collected. Initial findings are presented on a case study basis relating to patterns of feeder currents and EV charging, coincidence of EV load, Esprit function in practice, and the reliability of PLC
Parents' responses to receiving sickle cell or cystic fibrosis carrier results for their child following newborn screening.
No full textUniversal newborn screening for sickle cell disorders and cystic fibrosis aims to enable the early identification and treatment of affected babies. Screening can also identify infants who are healthy carriers, with carrier results being the commonest outcome for parents and professionals to discuss in practice. However it is unclear what the effect will be on parents on being informed of their baby's carrier result. Semi-structured face-to-face interviews were conducted with a purposeful sample of 67 family members (49 mothers, 16 fathers, 2 grandparents) of 51 infants identified by universal newborn screening as carriers of cystic fibrosis (n=27) and sickle cell (n=24), across all health regions in England. Data were analysed by thematic analysis with subsequent respondent validation. Untoward anxiety or distress among parents appeared influenced by how results were conveyed, rather than the carrier result per se. Parents who had more prior awareness of carrier status or the possibility of a carrier result assimilated the information more readily. Being left in an information vacuum while awaiting results, or before seeing a professional, led some parents to fear that their child had a serious health condition. Parental distress and anxiety appeared mostly transient, subsiding with understanding of carrier status and communication with a professional. Parents regarded carrier results as valuable information and sought to share this with their families and to inform their children in the future. However parents needed greater support after communication of results in considering and accessing cascade testing, and negotiating further communication within their families
Laboratory differences in relative expression factors generated for intestinal P-glycoprotein and Breast Cancer Resistance Protein: Relevance to in vitro-in vivo extrapolation
No full textIn Vitro-In Vivo Extrapolation (IVIVE) data from cell–based transport assays can be included within Physiologically-Based Pharmacokinetic (PBPK) models that aim to predict time-dependent profiles of drug disposition. For this purpose, drug-dependent kinetic transporter data (i.e., Jmax/Km) are combined with system-dependent data (e.g. tissue transporter expression in a population). Relative Expression Factors (REFs), the ratios of transporters’ expression in vivo to those in the in vitro system, are also required to gain realistic estimates of the mass of drug transferred across a membrane when scaling from in vitro data. Currently, these models have used relative measurements of intestinal transporter expression from immunoblotting1 rather than absolute abundances from quantitative targeted absolute proteomics (QTAP) techniques to generate intestinal REFs. The absolute protein abundances of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) were determined in Caco-2 cells and human distal jejunum enterocyte membranes using a QTAP quantification concatamer (QconCAT) strategy. Scalars for P-gp (REFiP-gp) and BCRP (REFiBCRP) were generated from these absolute abundance data and compared to immunoblotting scalars from the literature2,3. IVIVE-PBPK simulations using the Simcyp population-based simulator (Version 14 Release 1) were performed to assess the impact of absolute abundance or immunoblotting-based REFiP-gp on the plasma concentrations of the P-gp probe digoxin. To verify the relative contribution of intestinal P-gp to the overall intestinal transport of digoxin, the DDI with rifampicin, a P-gp inducer (3.5-fold4), was investigated. REFiBCRP was used to assess the regional-specific absorption and plasma concentrations of a theoretical compound (TC-1); a highly permeable, basic compound with BCRP intrinsic clearance, where jejunal absorption was highest and the fraction of dose absorbed (fa) in the jejunum was sensitive to alterations in small intestine transit time. There was a 5-fold lower REFiP-gp (0.4) generated from absolute abundance data compared to that generated by immunoblotting (2), providing a 1.2 and 1.3-fold higher area under the plasma concentration-time curve (AUC) and maximal plasma concentration (Cmax) for digoxin, respectively. REFiP-gp from both laboratories lead to digoxin Cmax values within observed ranges5,6. The P-gp activity data for digoxin were obtained from the same laboratory as the REFiP-gp from immunoblotting. When increasing the REFiP-gp from 0.4 from QTAP data to 1.4, to reflect rifampicin induced P-gp expression, this failed to capture the observed DDI, yet the DDI was recovered by inducing the immunoblot REF of 2 by 3.5-fold to 7. As expected, to recover the rifampicin DDI when using the induced REFiP-gp from QTAP data, a 4.2-fold higher Jmax is required.There was a 1.9-fold higher REFiBCRP (2.22) generated from absolute abundance data compared to immunoblotting (1.19), leading to a maximum 1.5-fold higher fa in the distal jejunum and a 1.2-fold higher Cmax for TC-1. When using REF¬iBCRP from both laboratories, a considerable overlap was demonstrated for Cmax across a population of 100 virtual individuals. Laboratory-specific differences in REFs may lead to different IVIVE-PBPK outcomes. While a wide-range of REFiP-gp could be used (0.1-to-5) to attain observed digoxin Cmax values, only a specific REF in combination with the corresponding in vitro kinetic data will allow a realistic recovery of the active contribution to the overall membrane transport. Furthermore, it was shown that inter-individual variability in other physiological parameters that govern fa and Cmax within each individual are more relevant than the differences in REFiBCRP of the currently available scalars. References:[1] Neuhoff et al., 2013, J Pharm Sci, 102: 3145-60. – [2] Troutman and Thakker, 2003, Pharm Res, 20: 1210-1224. – [3] Von Richter et al., 2009, Naunyn Schmiedebergs Arch Pharmacol, 379: 11-26. – [4] Greiner et al., 1999, J Clin Invest, 104: 147-53. – [5] Reitman et al., 2011, Clin Pharmacol Ther, 89: 234-42. – [6] Versufyft et al., 2003, Clin Pharmacol Ther, 73: 51-60
The Q/U Imaging Experiment: Polarization Measurements of Radio Sources at 43 and 95 GHz
No full textWe present polarization measurements of extragalactic radio sources observed during the cosmic microwave background polarization survey of the Q/U Imaging Experiment (QUIET), operating at 43 GHz (Q-band) and 95 GHz (W-band). We examine sources selected at 20 GHz from the public, >40 mJy catalog of the Australia Telescope (AT20G) survey. There are ˜480 such sources within QUIET’s four low-foreground survey patches, including the nearby radio galaxies Centaurus A and Pictor A. The median error on our polarized flux density measurements is 30-40 mJy per Stokes parameter. At signal-to-noise ratio > 3 significance, we detect linear polarization for seven sources in Q-band and six in W-band; only 1.3 ± 1.1 detections per frequency band are expected by chance. For sources without a detection of polarized emission, we find that half of the sources have polarization amplitudes below 90 mJy (Q-band) and 106 mJy (W-band), at 95% confidence. Finally, we compare our polarization measurements to intensity and polarization measurements of the same sources from the literature. For the four sources with WMAP and Planck intensity measurements >1 Jy, the polarization fractions are above 1% in both QUIET bands. At high significance, we compute polarization fractions as much as 10%-20% for some sources, but the effects of source variability may cut that level in half for contemporaneous comparisons. Our results indicate that simple models—ones that scale a fixed polarization fraction with frequency—are inadequate to model the behavior of these sources and their contributions to polarization maps
Performance Analysis of Energy Efficient Distributed Antenna Systems
No full textThere is a huge demand for data traffic caused by increased usage of data-hungry applications on smart mobile devices. This has resulted into cellular network expansion and upgrade that have increased energy costs and generated environmental concerns. Distributed antenna systems (DAS) are applied to enhance the coverage of the cell via geographically distributed antennas elements (DAEs) which are connected to the base station that is located at the centre of the cell. In this paper, DAS is proposed as a network solution to fulfill increasing capacity demands while addressing the energy efficiency (EE) and environmental concerns associated with cellular network operation. Maximum Ratio Transmission (MRT) and Fractional Frequency Reuse (FFR) are applied to calculate the downlink ergodic spectral efficiency (SE), EE and energy consumption ratio (ECR). Nakagami-m fading and log-normal shadowing are considered. Our results demonstrate that DAS using MRT and FFR increases the spectral and energy efficiency of the network compared to a basic cellular network system
IFNγ Signaling Endows DCs with the Capacity to Control Type I Inflammation during Parasitic Infection through Promoting T-bet+ Regulatory T Cells.
No full textIFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population
Self-harm and life problems: findings from the Multicentre Study of Self-harm in England.
No full textPURPOSE: Self-harm is a major clinical problem and is strongly linked to suicide. It is important to understand the problems faced by those who self-harm to design effective clinical services and suicide prevention strategies. We investigated the life problems experienced by patients presenting to general hospitals for self-harm. METHODS: Data for 2000-2010 from the Multicentre Study of Self-harm in England were used to investigate life problems associated with self-harm and their relationship to patient and clinical characteristics, including age, gender, repeat self-harm and employment status. RESULTS: Of 24,598 patients (36,431 assessed episodes), 57 % were female and with a mean age of 33.1 years (SD 14.0 years), 92.6 % were identified as having at least one contributing life problem. The most frequently reported problems at first episode of self-harm within the study period were relationship difficulties (especially with partners). Mental health issues and problems with alcohol were also very common (especially in those aged 35-54 years, and those who repeated self-harm). Those who repeated self-harm were more likely to report problems with housing, mental health and dealing with the consequences of abuse. CONCLUSIONS: Self-harm usually occurs in the context of multiple life problems. Clinical services for self-harm patients should have access to appropriate care for provision of help for relationship difficulties and problems concerning alcohol and mental health issues. Individualised clinical support (e.g. psychological therapy, interventions for alcohol problems and relationship counselling) for self-harm patients facing these life problems may play a crucial role in suicide prevention