Up-regulation of the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) by autoantibodies in autoimmune vasculitis

Autoimmune vasculitis is characterized by the presence of autoantibodies, particularly anti-neutrophil cytoplasmic antibodies (ANCA) and anti-nuclear antibodies (ANA), in patient sera. These autoantibodies have an incompletely understood role in development of vascular injury. The expression or up-regulation of cell adhesion molecules is an early phase in the development of an inflammatory vascular lesion. Autoantibody-positive sera from patients with vasculitis were assessed for their ability to modulate adhesion molecule expression by human umbilical vein endothelial cells (HUVEC). Autoantibody-positive serum samples from 11 out of 21 patients with primary vasculitis produced substantial up-regulation of ICAM-1 on HUVEC. Autoantibody-negative samples did not produce adhesion molecule up-regulation. Up-regulation of adhesion molecules on HUVEC was observed with samples positive for ANA, a phenomenon not previously reported. Preincubation of the sera with purified antigens recognized by ANCA failed to block this activation. In addition, MoAbs to ANCA antigens were ineffective at inducing ICAM-1 up-regulation, suggesting that activation is independent of the molecular specificity of the antibody. This capacity of ANCA- and ANA-positive sera to up-regulate adhesion molecules on endothelial cells may be a factor in the vessel wall inflammation seen in ANCA-associated vasculitis.

Up-regulation of the granulocyte adhesion molecule Mac-1 by autoantibodies in autoimmune vasculitis

The characteristic finding of autoantibodies in patients with vasculitis has raised the possibility that these antibodies play a role in the pathogenesis of the disease. The expression of adhesion molecules (AM) on leucocytes and endothelial cells is believed to be integral to the development of vasculitis. We therefore investigated the effect of sera, positive for anti-neutrophil cytoplasmic antibodies (ANCA) or anti-nuclear antibodies (ANA) from patients with vasculitis, on granulocyte expression of the adhesion molecule Mac-1 (CD11b). Autoantibody-positive sera from 15 out of 35 patients with vasculitis stimulated an up-regulation of Mac-1 on granulocytes. In most cases this effect was reproduced by the autoantibody-positive purified IgG fraction. Autoantibody-negative samples did not stimulate AM up-regulation. Of interest, preincubation of sera with purified antigens did not inhibit AM up-regulation by the autoantibody samples. Blocking the Fc receptors on granulocytes did result in a decrease of Mac-1 up-regulation, but this trend was not statistically significant. These results suggest that both ANCA and ANA have the capacity to up-regulate granulocyte AM expression, and that while Fc interaction with granulocyte Fc receptors is important, it is not the only mechanism whereby such autoantibodies activate cells.

Older people and legal advice – the need for joined up and creative approaches

This paper reports the findings from research conducted with older people in Northern
Ireland which investigated whether their needs for legal information and advice were
being met. One of the unique aspects of the research involved investigating the
potential of the internet as a possible source for advising older people in relation to
legal problems. The findings suggest that online legal information may frequently assist
older people in identifying potential answers to their legal questions, but may not be an
adequate substitute for personal communication and advice. The research also
highlights the need for professionals to work together to meet the needs of older
persons for legal advice and to safeguard their interests. Such ‘joined up’ approaches
are particularly important, for example at the point of dementia diagnosis, where
information sharing between health and social care professionals may significantly
promote the legal and welfare interests of older people at a vulnerable point in their
lives. This paper therefore turns to work by university-based legal clinics in the United
States, such as the Elder Law Clinic at Pennsylvania State University, where social
work or healthcare professionals, lawyers and law students collaborate to support older
people in their search for resolution of legal problems.

Rijndael FPGA implementations utilising look-up tables

This paper presents single-chip FPGA Rijndael algorithm implementations of the Advanced Encryption Standard (AES) algorithm, Rijndael. In particular, the designs utilise look-up tables to implement the entire Rijndael Round function. A comparison is provided between these designs and similar existing implementations. Hardware implementations of encryption algorithms prove much faster than equivalent software implementations and since there is a need to perform encryption on data in real time, speed is very important. In particular, Field Programmable Gate Arrays (FPGAs) are well suited to encryption implementations due to their flexibility and an architecture, which can be exploited to accommodate typical encryption transformations. In this paper, a Look-Up Table (LUT) methodology is introduced where complex and slow operations are replaced by simple LUTs. A LUT-based fully pipelined Rijndael implementation is described which has a pre-placement performance of 12 Gbits/sec, which is a factor 1.2 times faster than an alternative design in which look-up tables are utilised to implement only one of the Round function transformations, and 6 times faster than other previous single-chip implementations. Iterative Rijndael implementations based on the Look-Up-Table design approach are also discussed and prove faster than typical iterative implementations.

Numbered-up gas-liquid micro/milli channels reactor with modular flow distributor

Gas-liquid processing in microreactors remains mostly restricted to the laboratory scale due to the complexity and expenditure needed for an adequate numbering-up with a uniform flow distribution. Here, the numbering-up is presented for multi-phase (gas-liquid) flow in microreactor suitable for a production capacity of kg/h. Based on the barrier channels concept, the barrier-based micro/milli reactor (BMMR) is designed and fabricated to deliver flow non-uniformity of less than 10%. The BMMR consists of eight parallel channels all operated in the Taylor flow regime and with a liquid flow rate up to 150. mL/min. The quality of the flow distribution is reported by studying two aspects. The first aspect is the influence of different viscosities, surface tensions and flow rates. The second aspect is the influence of modularity by testing three different reaction channels type: (1) square channels fabricated in a stainless steel plate, (2) square channels fabricated in a glass plate, and (3) circular channels (capillaries) made of stainless steel. Additionally, the BMMR is compared to that of a single channel regard the slug and bubble lengths and bubble generation frequency. The results pave the ground for bringing multi-phase flow in microreactor one step closer for large scale production via numbering-up. © 2012 Elsevier B.V.

Joined-up government in Ireland:From un-strategic choices to patriotic imperatives

Over the last decade, joined-up government has assumed a prominent place in the study and practice of public management. In this article, drawing on the Irish case we adopt an institutionalist approach to the issue of joining-up government and bureaucratic reform. We explore how the period of sustained and rapid economic growth in Ireland during the 1990s was also characterised by a fragmentation of the public service and proliferation of agencies. Subsequently, as a consequence of the sharp contraction in public spending brought about by the global financial crisis, we find an accelerated process of public sector recentralisation, retrenchment and de-agencification. Much of this is occurring in an unplanned manner but under the generic banner of 'joining up' government. We identify the drivers behind these dynamics and how they have manifested themselves, as well as the changes to politicaladministrative relationships brought about by new initiatives, the power imbalances they expose, and ultimately their consequences on public service delivery. © Taylor & Francis Group, LLC.

The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model

Voltage-gated sodium channels (VGSC) have been linked to inherited forms of epilepsy. The expression and biophysical properties of VGSC in the hippocampal neuronal culture model have not been clarified. In order to evaluate mechanisms of epileptogenesis that are related to VGSC, we examined the expression and function of VGSC in the hippocampal neuronal culture model in vitro and spontaneously epileptic rats (SER) in vivo. Our data showed that the peak amplitude of transient, rapidly–inactivating Na+ current (INa,T) in model neurons was significantly increased compared with control neurons, and the activation curve was shifted to the negative potentials in model neurons in whole cell recording by patch–clamp. In addition, channel activity of persistent, non-inactivating Na+ current (INa,P) was obviously increased in the hippocampal neuronal culture model as judged by single–channel patch–clamp recording. Furthermore, VGSC subtypes NaV1.1, NaV1.2 and NaV1.3 were up-regulated at the protein expression level in model neurons and SER as assessed by Western blotting. Four subtypes of VGSC proteins in SER were clearly present throughout the hippocampus, including CA1, CA3 and dentate gyrus regions, and neurons expressing VGSC immunoreactivity were also detected in hippocampal neuronal culture model by immunofluorescence. These findings suggested that the up-regulation of voltage-gated sodium channels subtypes in neurons coincided with an increased sodium current in the hippocampal neuronal culture model, providing a possible explanation for the observed seizure discharge and enhanced excitability in epilepsy.

Lay-up optimization of composite plates to delay mode-jump instabilities

Experimental and numerical studies have shown that the occurrence of abrupt secondary instabilities, or mode-jumps, in a postbuckling stiffened composite panel may initiate structural failure. This study presents an optimisation methodology, using a genetic algorithm and finite element analysis for the lay-up optimisation of postbuckling composite plates to delay the onset of mode-jump instabilities. A simple and novel approach for detecting modejumps is proposed, based on the RMS value of out-of-plane pseudo-velocities at a number of locations distributed over the postbuckling structure

Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months

To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants.

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.

Job Strain as a Risk Factor for Leisure-Time Physical Inactivity: An Individual-Participant Meta-Analysis of Up to 170,000 Men and Women

Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 19851988 to 20062008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50 women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 29 years. In cross-sectional analyses, the odds for physical inactivity were 26 higher (odds ratio 1.26, 95 confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21 higher (odds ratio 1.21, 95 confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21 and 20 higher for those with high-strain (odds ratio 1.21, 95 confidence interval: 1.11, 1.32) and passive (odds ratio 1.20, 95 confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.

A long-term follow-up of cognitive, emotional, and behavioural sequelae to Reye syndrome

Eighteen adolescents who had survived Reye syndrome (RS) in early childhood were assessed on cognitive, emotional, and behavioural variables in a second follow-up study tracking this group. Siblings were used as controls. The entire group with RS had survived with no obvious neurological damage at the first follow-up study. Indeed, current findings suggested that long-term cognitive, emotional, and behavioural functioning was comparable to siblings in approximately half of the group with RS. However, two factors were associated with a less favourable outcome. Cognitive, emotional, and behavioural functioning were significantly poorer in the subgroup of survivors whose illness had occurred in the first year of life. In addition, loss of consciousness, although the association with poor outcome was not as noticeable, was also associated with relative deficits on some scales of cognitive ability. Many of these deficits had not been obvious at the first follow-up and the importance of neurodevelopmental factors are considered. Finally, the implications of these findings for research and interventions in RS and other such encephalopathies are discussed.

Cooperative Learning in Science: Follow-up from primary to high school

This paper reports a two-year longitudinal study of the effects of cooperative learning on science attainment, attitudes towards science, and social connectedness during transition from primary to high school. A previous project on cooperative learning in primary schools observed gains in science understanding and in social aspects of school life. This project followed 204 children involved in the previous project and 440 comparison children who were not as they undertook transition from 24 primary schools to 16 high schools. Cognitive, affective, and social gains observed in the original project survived transition. The implications improving the effectiveness of school transition by using cooperative learning initiatives are explored. Possibilities for future research and the implications for practice and policy are discussed.