Protect our pubs!

Protect Our Pubs! is a project examining the notion of the nationalisation of pubs by the state. It involved a protest, audio tours of the pub, posters protesting at the notion, a contest for the smartest barperson, peg drinking contest, a flighting contest and various documentation. The protest and subsequent events took place at the Hare & Hounds Pub in the Midlands

Digital Media in a Special Educational Needs Classroom: A Study

PhDThis thesis presents a series of design-led case studies concerned with the use of digital technology and the practice of interaction design for children within the context of UK special educational needs classrooms. It explores the use and development of accessible digital systems to support groups of students who have a range of special educational needs. Working with groups of mixed ability students has found to be the most typical situation for teaching in the participant schools and is a rich but underexplored area of concern for interaction design research. This thesis presents detailed accounts and grounded analysis of four embedded, design-led, case studies in two UK special needs schools. It makes three main contributions to the community of researchers, designers and educational practitioners who are concerned with the use of digital technology with children and more specifically working within the field of interaction design for children with special educational needs. These contributions are: A set of design guidelines developed through an analysis of the detailed and thorough accounts of four embedded design-led research projects in two special needs school in the UK. A discussion of the development of the research approach taken in this thesis. A set of design personas of teaching staff interaction designers are likely to encounter when working in a UK special needs schoolRCUK under the Digital Economy Doctoral Training Centre scheme

Digital is dangerous debate: digital vs analogue

Images from the debate held as part of the Digital Is Dangerous project

Effect of heavy-intensity 'priming' exercise on oxygen uptake and muscle deoxygenation kinetics during moderate-intensity step-transitions initiated from an elevated work rate

We examined the effect of heavy-intensity ‘priming’ exercise on the rate of adjustment of pulmonary O2 uptake (τ 2p) initiated from elevated intensities. Fourteen men (separated into two groups: τ 2p≤25s [Fast] or τ 2p>25s [Slow]) completed step-transitions from 20W-to- 45%lactate threshold (LT; lower-step, LS) and 45%-to-90%LT (upper-step, US) performed (i) without; and (ii) with US preceded by heavy-intensity exercise (HUS). Breath-by-breath 2p and near-infrared spectroscopy-derived muscle deoxygenation ([HHb+Mb]) were measured. Compared to LS, τ 2p was greater (p0.05) from LS or Fast group US. In Slow, τ[HHb+Mb] increased (p<0.05) in US relative to HUS; this finding coupled with a reduced τ 2p indicates a priming-induced improvement in matching of muscle O2 delivery-to-O2 utilization during transitions from elevated intensities in those with Slow but not Fast 2p kinetics

A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis.

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted

Identification of PDL-1 as a novel biomarker of sensitizer exposure in dendritic-like cells

The development of novel in vitro methods to assess risks of allergic sensitization are essential in reducing animal testing whilst maintaining consumer safety. The main research objectives of this study were to identify novel biomarkers to assess the sensitization predictability of chemicals. Phenotypic and cytokine responses of moDCs and MUTZ-3 cells were investigated following application of contact sensitizers; dinitrochlorobenzene (DNCB), cinnamaldehyde (Cin), eugenol (E), isoeugenol (IE), P-phenylenediamine (PPD) and non-sensitizers; salicyclic acid (SA) and sodium lauryl sulphate (SLS). CD86 was up-regulated on MUTZ-3 cells in response to DNCB, Cin and PPD, however, moDCs only modulated CD86 in response to DNCB and E. PDL-1 (Programmed death receptor ligand-1) proved a promising sensitization biomarker in MUTZ-3 cells where up-regulation occurred in response to DNCB, Cin, IE and PPD. Additionally, moDC-expressed PDL-1 was modulated in response to Cin, IE and E thus demonstrating improved sensitizer predictability when compared with CD86. MCP-1 and RANTES were identified as biomarkers of DNCB exposure but MCP-1 did not show any change in expression above controls for the other sensitizers investigated. However, RANTES was increased in MUTZ-3 cells by both DNCB and Cin. Our findings highlight novel biomarkers which, in MUTZ-3 cells, could be taken forward within a multiple biomarker in vitro assay ensuring strong and reliable predictability. © 2010 Elsevier Ltd

PD-L1 regulates the development, maintenance, and function of induced regulatory T cells

Both the programmed death (PD) 1–PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1−/− antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1–coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1−/−PD-L2−/− Rag−/− recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity

Heat flow at the spreading centers of the Guaymas Basin, Gulf of California

Fifty-four new heat flow measurements in the central troughs of the Guaymas basin support the hypothesis that they are sites of active intrusion. In the northern trough a distinct pattern of hydrothermal cooling is revealed, with venting along the western boundary fault of the trough. In the southern trough an analogous pattern is apparently superimposed upon a conductive cooling anomaly associated with a recent central intrusion. The discharge of thermal waters occurs along the boundary faults and through other faults associated with a possible horst block located in the north central floor of the southern trough. The heat flow patterns suggest that the intrusions are episodic and do not occur simultaneously along the length (15–40 km) of a spreading segment. A review of all available heat flow measurements for the Guaymas basin suggests that most of the recharge for a pervasive regional hydrothermal system is limited to the central depressions, with perhaps some contribution from pore water. The discharge of thermal waters occurs predominantly in the central depressions and possibly along the boundary transform faults and fracture zones. The regions of the basin more than a few kilometers in distance from the spreading axis, although presumably underlain by a hydrothermal system, are probably not the location of numerous vents or recharge zones

The influence of metabolic and circulatory heterogeneity on the expression of pulmonary oxygen uptake kinetics in humans

New Findings What is the central question of this study? The finding that pulmonary oxygen uptake (inline image) kinetics on transition to moderate exercise is invariant and exponential is consistent with a first-order reaction controlling inline image. However, slowed inline image kinetics when initiating exercise from raised baseline intensities challenges this notion. What is the main finding and its importance? Here, we demonstrate how a first-order system can respond with non-first-order response dynamics. Data suggest that progressive recruitment of muscle fibre populations having progressively lower mitochondrial density and slower microvascular blood flow kinetics can unify the seemingly contradictory evidence for the control of inline image on transition to exercise. We examined the relationship amongst baseline work rate (WR), phase II pulmonary oxygen uptake (inline image) time constant (inline image) and functional gain inline image during moderate-intensity exercise. Transitions were initiated from a constant or variable baseline WR. A validated circulatory model was used to examine the role of heterogeneity in muscle metabolism (inline image) and blood flow (inline image) in determining inline image kinetics. We hypothesized that inline image and GP would be invariant in the constant baseline condition but would increase linearly with increased baseline WR. Fourteen men completed three to five repetitions of ∆40 W step transitions initiated from 20, 40, 60, 80, 100 and 120 W on a cycle ergometer. The ∆40 W step transitions from 60, 80, 100 and 120 W were preceded by 6 min of 20 W cycling, from which the progressive ΔWR transitions (constant baseline condition) were examined. The inline image was measured breath by breath using mass spectrometry and a volume turbine. For a given ΔWR, both inline image (22–35 s) and GP (8.7–10.5 ml min−1 W−1) increased (P < 0.05) linearly as a function of baseline WR (20–120 W). The inline image was invariant (P < 0.05) in transitions initiated from 20 W, but GP increased with ΔWR (P < 0.05). Modelling the summed influence of multiple muscle compartments revealed that inline image could appear fast (24 s), and similar to in vivo measurements (22 ± 6 s), despite being derived from inline image values with a range of 15–40 s and inline image with a range of 20–45 s, suggesting that within the moderate-intensity domain phase II inline image kinetics are slowed dependent on the pretransition WR and are strongly influenced by muscle metabolic and circulatory heterogeneity