Control influence on trust and relational governance in the client-contractor dyad

The construction industry has in recent years witnessed a paradigm shift towards the use of more collaborative contracting relationships and integrated processes in an attempt to improve construction project delivery. Trust is central to the success of these contracting approaches and although efforts are usually aimed at improving trust relations in client-contractor relationships, there has so far been mixed findings on how trust is influenced by formal control mechanisms discharged via formal contracts. In construction contracting, there is therefore the need to investigate how different governance modes and control mechanisms deployed on construction projects are perceived by those being controlled and how this in turn influences trust. Through a critique of the extant literature on trust and control in construction, this study reveals that the trust-control relationship which can be both complimentary and supplementary has far reaching implications on the measurement/assessment of trust in the construction project context. The orientation of governance and control mechanisms selected by clients and the behavioural consequences of these from contractors can thus be used as a measure of the degree of trust that exists in the dyad

A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis

Planar microwave devices fabricated by ion-implantation patterning of high-temperature superconductors

We have applied ion-implantation inhibit patterning as a new method of fabricating low-loss microwave transmission lines in high-temperature superconductor thin films. To determine the effectiveness of this technique, we fabricated coplanar waveguide transmission lines in YBa2Cu3O7 – thin films that had been deposited on LaAlO3 substrates using pulsed laser deposition. Microwave characterizations of these lines are compared to a reference line fabricated with conventional ion milling. At 76 K and 12 GHz, the attenuation constants of the ion-implanted transmission lines are approximated 0.02 dB/mm, and the overall loss response is indistinguishable from that of the ion-milled device.published_or_final_versio

Implementation of a Quantum Search Algorithm on a Nuclear Magnetic Resonance Quantum Computer

We demonstrate an implementation of a quantum search algorithm on a two qubit NMR quantum computer based on cytosine.Comment: Six pages, three figure

Geometric quantum computation with NMR

The experimental realisation of the basic constituents of quantum information processing devices, namely fault-tolerant quantum logic gates, requires conditional quantum dynamics, in which one subsystem undergoes a coherent evolution that depends on the quantum state of another subsystem. In particular, the subsystem may acquire a conditional phase shift. Here we consider a novel scenario in which this phase is of geometric rather than dynamical origin. As the conditional geometric (Berry) phase depends only on the geometry of the path executed it is resilient to certain types of errors, and offers the potential of an intrinsically fault-tolerant way of performing quantum gates. Nuclear Magnetic Resonance (NMR) has already been used to demonstrate both simple quantum information processing and Berry's phase. Here we report an NMR experiment which implements a conditional Berry phase, and thus a controlled phase shift gate. This constitutes the first elementary geometric quantum computation.Comment: Minor additions at request of referees. 4 pages revtex including 2 figures (1 eps). Nature in pres

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Effect of nickel on the microstructure and mechanical property of die-cast Al–Mg–Si–Mn alloy

The effect of nickel on the microstructure and mechanical properties of a die-cast Al–Mg–Si–Mn alloy has been investigated. The results show that the presence of Ni in the alloy promotes the formation of Ni-rich intermetallics. These occur consistently during solidification in the die-cast Al–Mg–Si–Mn alloy across different levels of Ni content. The Ni-rich intermetallics exhibit dendritic morphology during the primary solidification and lamellar morphology during the eutectic solidification stage. Ni was found to be always associated with iron forming AlFeMnSiNi intermetallics, and no Al3Ni intermetallic was observed when Ni concentrations were up to 2.06 wt% in the alloy. Although with different morphologies, the Ni-rich intermetallics were identified as the same AlFeMnSiNi phase bearing a typical composition of Al[100–140](Fe,Mn)[2–7]SiNi[4–9]. With increasing Ni content, the spacing of the α-Al–Mg2Si eutectic phase was enlarged in the Al–Mg–Si–Mn alloy. The addition of Ni to the alloy resulted in a slight increase in the yield strength, but a significant decrease in the elongation. The ultimate tensile strength (UTS) increased slightly from 300 to 320 MPa when a small amount (e.g. 0.16 wt%) of Ni was added to the alloy, but further increase of the Ni content resulted in a decrease of the UTS.The Engineering and Physical Sciences Research Council (EPSRC), Technology Strategy Board (TSB) and Jaguar Land Rover (JLR) in the United Kingdom

Electrosprayed core-shell nanoparticles of PVP and shellac for furnishing biphasic controlled release of ferulic acid

Coaxial electrospraying was explored to organize polymer excipients in a core-shell manner for providing biphasic controlled release of active ingredient. With ferulic acid (FA) as a model drug, and shellac and polyvinylpyrrolidone (PVP) as the core and shell polymeric matrices, core-shell nanoparticles were successfully fabricated. A series of tests were carried out to characterize the prepared core-shell nanoparticles and also the nanoparticles prepared using a single fluid electrospraying of the shell or core fluids alone. The core-shell nanoparticles had an average diameter of 530 ± 80 nm with clear core-shell structure. The contained FA was converted to an amorphous state both in the core and the shell parts due to the favorable hydrogen bonding between the components. In vitro dissolution tests demonstrated that the core-shell nanoparticles were able to provide the desired biphasic drug-controlled release profiles. Coaxial electrospraying is a useful tool for the development of novel nanodrug delivery systems from polymers

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis