Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene therapy for the treatment of β-thalassemia

Gene therapy is one potential novel therapeutic avenue for the treatment of inherited monogenic disorders. Diseases of the blood are frequent targets for gene therapy because it is relatively easy to harvest haematopoietic stem cells (HSCs) from the bone marrow, genetically modify the cells ex vivo, and then re-administer the corrected cells back into the patient via intra-venous injection. In this Closeup, Milsom and Williams discuss the work of Roselli et al, who describe the pre-clinical evaluation of the treatment for β-thalassemia in erythroid cells via the genetic correction of patient HSCs using a lentiviral vector

Coastal scenic assessment : unlocking the potential for coastal tourism in rural Pakistan via Mediterranean developed techniques

Originally developed within the Mediterranean, a tested coastal management and planning tool was applied outside the region to evaluate its international scope, with particular reference to a less developed country. Seven coastal sites in Pakistan were investigated for their scenic values through a 26 item checklist grouped as physical and human parameters analysed though weighted parameters and fuzzy logic matrices. With respect to a five-class evaluation system, results indicated: Jiwani, Miani Hor and Pasni-Astola Island as extremely attractive natural sites with very high landscape value (classified as Class 1 sites); Mubarak village as an attractive natural site with high landscape value (classified as a Class 2 site); Kaka pir village, Harjana village and Keti Bandar as having little outstanding landscape features or with urban environment and classified as Class 3 sites. Rural and/or urban environmental influences were observed to be critical factors which influenced major human parameters that ultimately affect sites’ scenic classification. However, notwithstanding natural attraction, unless political and social development barriers are tackled in conjunction with recognising areas that possess inherent tourism potential, economic potential is unlikely to be realised.peer-reviewe

Higher Education and Society: A research report

This report draws on a substantial body of research undertaken by the Open University's Centre for Higher Education Research and Information (CHERI) on the changing relationships between higher education and society. Higher education currently faces many changes, some externally driven by government policies and changing patterns of social and economic demand and some internally driven by changes in the way knowledge is produced and organised within universities and other 'knowledge organisations'. CHERI examines these changes through empirical research which is policy relevant though not policy dictated, frequently international, and broadly focused on the social impacts of higher education. Does higher education make a difference and to whom? In their different ways, the articles in this report seek to provide answers to this important but difficult question

What do self-efficacy items measure? : Examining the discriminant content validity of self-efficacy items

© 2018 The British Psychological Society.Peer reviewedPostprin

Efficacy and Safety of Abacavir/Lamivudine/Zidovudine Plus Tenofovir in HBV/HIV-1 Coinfected Adults: 48-Week Data

In HBV/HIV-coinfected patients, the risk of end-stage liver disease and death is increased. This open-label, prospective, pilot study evaluated abacavir/lamivudine/zidovudine twice daily plus tenofovir once daily in HBV/HIV-coinfected antiretroviral-naïve subjects. Nine adults (8 males) enrolled, with baseline mean HIV-1 RNA = 4.5 log10 copies/mL, HBV DNA = 9.0 log10 copies/mL, and median CD4 count =158 cells/mm3. No subject had baseline ALT >5x ULN

A Controlled Study on the Characterisation of Bioaerosols Emissions from Compost

Bioaerosol emissions arising from biowaste treatment are an issue of public concern. To better characterise the bioaerosols, and to assess a range of measurement methods, we aerosolised green waste compost under controlled conditions. Viable and non-viable Andersen samplers, cyclone samplers and a real time bioaerosol detection system (Spectral Intensity Bioaerosol Sensor (SIBS)) were deployed simultaneously. The number-weighted fraction of fluorescent particles was in the range 22–26% of all particles for low and high emission scenarios. Overall fluorescence spectral profiles seen by the SIBS exhibited several peaks across the 16 wavelength bands from 298 to 735 nm. The size-fractionated endotoxin profile showed most endotoxin resided in the 2.1–9 μm aerodynamic diameter fraction, though up to 27% was found in a finer size fraction. A range of microorganisms were detected through culture, Matrix Assisted Laser Desorption and Ionisation Time of Flight Mass Spectrometry (MALDI-TOF) and quantitative polymerase chain reaction (qPCR), including Legionella pneumophila serogroup 1. These findings contribute to our knowledge of the physico-chemical and biological characteristics of bioaerosols from composting sites, as well as informing future monitoring approaches and data interpretation for bioaerosol measurement

Guanine Nucleotide Exchange Factor Vav1 Regulates Perivascular Homing and Bone Marrow Retention of Hematopoietic Stem and Progenitor Cells

Engraftment and maintenance of hematopoietic stem and progenitor cells (HSPC) depend on their ability to respond to extracellular signals from the bone marrow microenvironment, but the critical intracellular pathways integrating these signals remain poorly understood. Furthermore, recent studies provide contradictory evidence of the roles of vascular versus osteoblastic niche components in HSPC function. To address these questions and to dissect the complex upstream regulation of Rac GTPase activity in HSPC, we investigated the role of the hematopoietic-specific guanine nucleotide exchange factor Vav1 in HSPC localization and engraftment. Using intravital microscopy assays, we demonstrated that transplanted $Vav1^{−/−}$ HSPC showed impaired early localization near $nestin^+$ perivascular mesenchymal stem cells; only 6.25% of $Vav1^{−/−}$ HSPC versus 45.8% of wild-type HSPC were located less than 30 μm from a $nestin^+$ cell. Abnormal perivascular localization correlated with decreased retention of $Vav1^{−/−}$ HSPC in the bone marrow (44–60% reduction at 48 h posttransplant, compared with wild-type) and a very significant defect in short- and long-term engraftment in competitive and noncompetitive repopulation assays (<1.5% chimerism of $Vav1^{−/−}$ cells vs. 53–63% for wild-type cells). The engraftment defect of $Vav1^{−/−}$ HSPC was not related to alterations in proliferation, survival, or integrin-mediated adhesion. However, $Vav1^{−/−}$ HSPC showed impaired responses to $SDF1\alpha$, including reduced in vitro migration in time-lapse microscopy assays, decreased circadian and pharmacologically induced mobilization in vivo, and dysregulated Rac/Cdc42 activation. These data suggest that Vav1 activity is required specifically for $SDF1\alpha$-dependent perivascular homing of HSPC and suggest a critical role for this localization in retention and subsequent engraftment

Coherent Tunneling of Atoms from Bose-condensed Gases at Finite Temperatures

Tunneling of atoms between two trapped Bose-condensed gases at finite temperatures is explored using a many-body linear response tunneling formalism similar to that used in superconductors. To lowest order, the tunneling currents can be expressed quite generally in terms of the single-particle Green's functions of the isolated Bose gases. A coherent first-order tunneling Josephson current between two atomic Bose-condensates is found, in addition to coherent and dissipative contributions from second-order condensate-noncondensate and noncondensate-noncondensate tunneling. Our work is a generalization of Meier and Zwerger, who recently treated tunneling between uniform atomic Bose gases. We apply our formalism to the analysis of an out-coupling experiment induced by light wave fields, using a simple Bogoliubov-Popov quasiparticle approximation for the trapped Bose gas. For tunneling into the vacuum, we recover the results of Japha, Choi, Burnett and Band, who recently pointed out the usefulness of studying the spectrum of out-coupled atoms. In particular, we show that the small tunneling current of noncondensate atoms from a trapped Bose gas has a broad spectrum of energies, with a characteristic structure associated with the Bogoliubov quasiparticle u^2 and v^2 amplitudes.Comment: 26 pages, 5 figures, minor changes, to appear in PR

The Passive Journalist: How sources dominate the local news

This study explores which sources are “making” local news and whether these sources are simply indicating the type of news that appears, or are shaping newspaper coverage. It provides an empirical record of the extent to which sources are able to dominate news coverage from which future trends in local journalism can be measured. The type and number of sources used in 2979 sampled news stories in four West Yorkshire papers, representing the three main proprietors of local newspapers in the United Kingdom, were recorded for one month and revealed the relatively narrow range of routine sources; 76 per cent of articles cited only a single source. The analysis indicates that journalists are relying less on their readers for news, and that stories of little consequence are being elevated to significant positions, or are filling news pages at the expense of more important stories. Additionally, the reliance on a single source means that alternative views and perspectives relevant to the readership are being overlooked. Journalists are becoming more passive, mere processors of one-sided information or bland copy dictated by sources. These trends indicate poor journalistic standards and may be exacerbating declining local newspaper sales