Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil red-O-positive active plaques but less frequent in NAWM (15%), and in normal (

Elucidation of the controlling steps of reactive dyes adsorption on activated carbon

In this work, the rate-limiting steps of reactive dye adsorption onto FS-400 activated carbon were elucidated through the investigation of adsorption kinetics. These studies initially revealed that only 20% of the available adsorption capacity was achieved during the first 6 h of mixing. Kinetic profiles showed that the adsorption process was mainly controlled by external diffusion during the first 30 min of the reaction, after which internal diffusion controlled the process. The interruption test method identified the rate-limiting steps; the results showed that sorption of reactive dyes onto FS-400 was mainly controlled by internal diffusion. Furthermore, the external and internal diffusion coefficients and the desorption rate decreased after the interruption period. The same parameters increased when the solution temperature was raised. The thermodynamic parameters studied showed that the adsorption of reactive dyes onto activated carbon was endothermic and is mainly controlled by internal diffusion with a minor effect of external diffusion.

Expression of the common heat-shock protein receptor CD91 is increased on monocytes of exposed yet HIV-1-seronegative subjects.

The significantly higher surface expression of the surface heat-shock protein receptor CD91 on monocytes of human immunodeficiency virus type-1 (HIV-1)-infected, long-term nonprogressors suggests that HIV-1 antigen uptake and cross-presentation mediated by CD91 may contribute to host anti-HIV-1 defenses and play a role in protection against HIV-1 infection. To investigate this further, we performed phenotypic analysis to compare CD91 surface expression on CD14+ monocytes derived from a cohort of HIV-1-exposed seronegative (ESN) subjects, their seropositive (SP) partners, and healthy HIV-1-unexposed seronegative (USN) subjects. The median fluorescent intensity (MFI) of CD91 on CD14+ monocytes was significantly higher in ESN compared with SP (P=0.028) or USN (P=0.007), as well as in SP compared with USN subjects (P=0.018). CD91 MFI was not normalized in SP subjects on highly active antiretroviral therapy (HAART) despite sustainable, undetectable plasma viraemia. Data in three SP subjects experiencing viral rebounds following interruption of HAART showed low CD91 MFI comparable with levels in USN subjects. There was a significant positive correlation between CD91 MFI and CD8+ T cell counts in HAART-naïve SP subjects (r=0.7, P=0.015). Increased surface expression of CD91 on CD14+ monocytes is associated with the apparent HIV-1 resistance that is observed in ESN subjects.

Catalyst distribution and carbon nanotube morphology in multilayer forests by mixed CVD processes

Carbon nanotubes can be grown as forests of aligned fibers on a substrate with a catalyst coated prior to or added during synthesis. A major process interruption can initiate the growth of second and successive layers of forest on top or at the base of the existing layers which are thereby lifted up. We report on the generation of multilayer CNT forests where the first forest is generated either by catalyst coinjection (CCI) of ferrocene with hydrocarbon (xylene) or by catalyst predeposition (CPD) of iron followed with hydrocarbon (acetylene). Subsequent layers are then produced by CCI alone to give uniform (all CCI) or mixed (CPD and CCI) structures to study the distribution of the iron catalyst and CNT morphology and to determine whether the CPD forest templates or otherwise influences the growth of subsequent CCI forests. The bottom-up base growth of second and subsequent CCI forests is reaction rate controlled. CCI multilayer forests accumulate catalyst (iron) in a variety of distinct locations. A pre-existing CPD forest modifies subsequent CCI forest initiation, morphology, and catalyst distribution but does not itself accumulate catalyst or change appearance. © 2009 American Chemical Society.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

Impact of community based, specialist palliative care teams on hospitalisations and emergency department visits late in life and hospital deaths: a pooled analysis

Objective: To determine the pooled effect of exposure to one of 11 specialist palliative care teams providing services in patients’ homes.Design: Pooled analysis of a retrospective cohort study.Setting: Ontario, Canada.Participants: 3109 patients who received care from specialist palliative care teams in 2009-11 (exposed) matched by propensity score to 3109 patients who received usual care (unexposed).Intervention: The palliative care teams studied served different geographies and varied in team composition and size but had the same core team members and role: a core group of palliative care physicians, nurses, and family physicians who provide integrated palliative care to patients in their homes. The teams’ role was to manage symptoms, provide education and care, coordinate services, and be available without interruption regardless of time or day.Main outcome measures: Patients (a) being in hospital in the last two weeks of life; (b) having an emergency department visit in the last two weeks of life; or (c) dying in hospital.Results: In both exposed and unexposed groups, about 80% had cancer and 78% received end of life homecare services for the same average duration. Across all palliative care teams, 970 (31.2%) of the exposed group were in hospital and 896 (28.9%) had an emergency department visit in the last two weeks of life respectively, compared with 1219 (39.3%) and 1070 (34.5%) of the unexposed group (P<0.001). The pooled relative risks of being in hospital and having an emergency department visit in late life comparing exposed versus unexposed were 0.68 (95% confidence interval 0.61 to 0.76) and 0.77 (0.69 to 0.86) respectively. Fewer exposed than unexposed patients died in hospital (503 (16.2%) v 887 (28.6%), P<0.001), and the pooled relative risk of dying in hospital was 0.46 (0.40 to 0.52).Conclusions: Community based specialist palliative care teams, despite variation in team composition and geographies, were effective at reducing acute care use and hospital deaths at the end of life.

Securing the smart grid

The availability of electricity is fundamental to modern society. It is at the top of the list of critical infrastructures and its interruption can have severe consequences. This highly important system is now evolving to become more reliable, efficient, and clean. This evolving infrastructure has become known as the smart grid; and these future smart grid systems will rely heavily on ICT. This infrastructure will require many servers and due to the nature of the grid, many of these systems will be geographically diverse requiring communication links. At the heart of this ICT infrastructure will be security. At each level of the smart grid from smart metering right through to remote sensing and control networks, security will be a key factor for system design consideration. With an increased number of ICT systems in place the security risk also increases. In this paper the authors discuss the changing nature of security in relation to the smart grid by looking at the move from legacy systems to more modern smart grid systems. The potential planes of attack for future smart grid systems are identified, and the general anatomy of a cyber-attack is presented. The authors then introduce the various threat levels of different types of attack and the mitigation techniques that could be put in place for each. Finally, the authors' introduce a Phasor Measurement Unit (PMU) communication system (operated by the authors) that can be used as a test-bed for some of the proposed future security research.

Assessment Of various sensors for structural health monitoring for bridge weigh-in-motion (B-WIM).

In recent years, Structural Health Monitoring (SHM) systems have been developed to monitor bridge deterioration, assess real load levels and hence extend bridge life and safety. A road bridge is only safe if the stresses caused by the passing vehicles are less than the capacity of the bridge to resist them. Conventional SHM systems can be used to improve knowledge of the bridges capacity to resist stresses but generally give no information on the causes of any increase in stresses (based on measuring strain). The concept of in Bridge Weigh-in-Motion (B-WIM) is to establish axle loads, without interruption to traffic flow, by using strain sensors at a bridge soffit and subsequently converting the data to real time axle loads or stresses. Recent studies have shown it would be most beneficial to develop a portable system which can be easily attached to existing and new bridge structures for a specified monitoring period. The sensors could then be left in place while the data acquisition can be moved for various other sites. Therefore it is necessary to find accurate sensors capable of capturing peak strains under dynamic load and suitable methods for attaching these strain sensors to existing and new bridge structures. Additionally, it is important to ensure accurate strain transfer between concrete and steel, the adhesives layer and the strain sensor. This paper describes research investigating the suitably of using various sensors for the monitoring of concrete structures under dynamic vehicle load. Electrical resistance strain (ERS) gauges, vibrating wire (VW) gauges and fibre optic sensors (FOS) are commonly used for SHM. A comparative study will be carried out to select a suitable sensor for a bridge Weigh in Motion System. This study will look at fixing methods, durability, scanning rate and accuracy range. Finite element modeling is used to predict the strains which are then validated in laboratory trials.

Petal-rod - A Novel Method of Lightweighting

Lightweighting the preform to reduce material cost is possibly reaching its limit; key areas of the bottle however may deserve closer attention. The lack of material stretching at the bottle base insists on increased thickness to compensate for the impaired strength in this area. To improve this phenomenon, design of a novel stretch-rod that can mechanically stretch the preform tip during the ISBM process has been developed.

PETAL-ROD is a device that can be retrofitted to existing ISBM machines with minimum interruption to production rate, with the added benefit that material characteristics similar to the sidewall of the bottle can be achieved in the area of the base. Coupled with an optimized preform design, material weight saving can be improved.

‘New’ migrant identities: unravelling opportunities and restrictions

Labour and capital mobility from globalisation has given rise to significant increases in the reliance of migrant labour in established gateways, but also in new migration destinations. Many aspects of migrant incorporation in new migration destinations have received some attention, not least regarding employer and employee relations. Less attention has been focused on the construction of migrant as a marker of identification, although identities, particularly regarding gender and ethnicity, in the workplace have received considerable attention. This article aims to illuminate knowledge on how migration produces social change thereby responding to a call from Batnitzky et al. (2009, p. 1290) for additional attention on what ‘the practical and symbolic effects of migration are as people move across different structures and institutions of social control….’ Mindful of Goffman’s (1969, 1983) emphasis on individual interactions and experiences, it examines what it means to be a migrant in terms of everyday encounters and experiences. It investigates the array and interplay of internal and external processes that create migrant identities and the implications of this for social integration.

The paper argues that one of the paradoxes of globalisation, and of the associated increased levels of migrant labour, is the construction of the migrant identity that ultimately impedes social integration. It shows how the application of migrant identity (internally and externally) bestows a particular status that affects (options for) individual behaviour and subsequent actions and outcomes. The paper argues that while migrants value the migrant identity status because of the benefits that it brings, this status can also cause high levels of dissatisfaction among migrants and it can exclude migrants from wider benefits of full citizenship. Migrants have individual identification processes, but external forces, including social structures and institutions, also affect migrant identity. These forces help to shape individual expectations and standards, contributing to identity interruption and dissonance.

The paper is structured as follows: it uses social identity theory as a means of understanding what it is to be a ‘migrant’ in a new destination, while simultaneously recognising the inevitability of this generic label - migrants are an extremely heterogeneous group, made up of individuals with different experiences, values and so forth. The analysis considers the significance of context and of social interactions, thus paying attention to how identity is constructed and performed by the individual and also assigned by others. Empirical evidence is used to examine how having a migrant status affects individual prospects. The paper evaluates the extent to which patterns and processes of migration present an opportunity for social change, positive or negative.