The TWEAK/Fn14/CD163 axis - Implications for metabolic disease

TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK – Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression

A management architecture for active networks

In this paper we present an architecture for network and applications management, which is based on the Active Networks paradigm and shows the advantages of network programmability. The stimulus to develop this architecture arises from an actual need to manage a cluster of active nodes, where it is often required to redeploy network assets and modify nodes connectivity. In our architecture, a remote front-end of the managing entity allows the operator to design new network topologies, to check the status of the nodes and to configure them. Moreover, the proposed framework allows to explore an active network, to monitor the active applications, to query each node and to install programmable traps. In order to take advantage of the Active Networks technology, we introduce active SNMP-like MIBs and agents, which are dynamic and programmable. The programmable management agents make tracing distributed applications a feasible task. We propose a general framework that can inter-operate with any active execution environment. In this framework, both the manager and the monitor front-ends communicate with an active node (the Active Network Access Point) through the XML language. A gateway service performs the translation of the queries from XML to an active packet language and injects the code in the network. We demonstrate the implementation of an active network gateway for PLAN (Packet Language for Active Networks) in a forty active nodes testbed. Finally, we discuss an application of the active management architecture to detect the causes of network failures by tracing network events in time

A re-appraisal of the reliability of the 20 m multi-stage shuttle run test

This is the author's PDF version of an article published in European journal of applied physiology in 2007. The original publication is available at www.springerlink.co

Online test purchased new psychoactive substances in 5 different European countries; a snapshot study of chemical composition and price

Background: New psychoactive substances (NPS) are on offer worldwide online, in order to shed light on the purity and price of these substances in the European Union, a research collaboration was set up involving France, United Kingdom (UK), the Netherlands, Czech Republic and Poland. Methods: Per country, around 10 different NPS were test purchased from different webshops. Then, chemical analysis of NPS was done with according reference standards to identify and quantify the contents. Results: In contrast to what is generally advertised on the webshops (>99%), purity varied considerably per test purchased NPS. Several NPS were mislabelled, some containing chemical analogues (e.g. 25B/C-NBOMe instead of 25I-NBOMe, pentedrone instead of 3,4- DMMC). But in some cases NPS differed substantially from what was advertised (e.g. pentedrone instead of AMT or 3-FMC instead of 5-MeO-DALT). Per gram, purity-adjusted prices of cathinones differed substantially between three countries of test purchase, with Poland being the least expensive. Synthetic cannabinoids were relatively the most expensive in the Czech Republic and least expensive in the UK. Conclusions: The current findings provides a snapshot of the price and chemical contents of NPS products purchased by different countries and in different webshops. There is a potential danger of mislabelling of NPS. The great variety in price and purity of the delivered products might be the result of the market dynamics of supply and demand and the role of law enforcement in different European countries

The impact of measurement error in modelled ambient particles exposures on health effect estimates in multi-level analysis: a simulation study.

Background: Various spatiotemporal models have been proposed for predicting ambient particulate exposure for inclusion in epidemiological analyses. We investigated the effect of measurement error in the prediction of particulate matter with diameter <10 µm (PM10) and <2.5 µm (PM2.5) concentrations on the estimation of health effects. Methods: We sampled 1,000 small administrative areas in London, United Kingdom, and simulated the “true” underlying daily exposure surfaces for PM10 and PM2.5 for 2009–2013 incorporating temporal variation and spatial covariance informed by the extensive London monitoring network. We added measurement error assessed by comparing measurements at fixed sites and predictions from spatiotemporal land-use regression (LUR) models; dispersion models; models using satellite data and applying machine learning algorithms; and combinations of these methods through generalized additive models. Two health outcomes were simulated to assess whether the bias varies with the effect size. We applied multilevel Poisson regression to simultaneously model the effect of long- and short-term pollutant exposure. For each scenario, we ran 1,000 simulations to assess measurement error impact on health effect estimation. Results: For long-term exposure to particles, we observed bias toward the null, except for traffic PM2.5 for which only LUR underestimated the effect. For short-term exposure, results were variable between exposure models and bias ranged from −11% (underestimate) to 20% (overestimate) for PM10 and of −20% to 17% for PM2.5. Integration of models performed best in almost all cases. Conclusions: No single exposure model performed optimally across scenarios. In most cases, measurement error resulted in attenuation of the effect estimate

The information needs of people living with ankylosing spondylitis: a questionnaire survey

&lt;p&gt;BACKGROUND:Today, health care is patient-centred with patients more involved in medical decision making and taking an active role in managing their disease. It is important that patients are appropriately informed about their condition and that their health care needs are met. We examine the information utilisation, sources and needs of people with ankylosing spondylitis (AS).&lt;/p&gt; &lt;p&gt;METHODS: Participants in an existing AS cohort study were asked to complete a postal or online questionnaire containing closed and open-ended questions, regarding their information access and needs. Participants were stratified by age and descriptive statistics were performed using STATA 11, while thematic analysis was performed on open-ended question narratives. Qualitative data was handled in Microsoft Access and explored for emerging themes and patterns of experiences.&lt;/p&gt; &lt;p&gt;RESULTS: Despite 73% of respondents having internet access, only 49% used the internet to access information regarding AS. Even then, this was only infrequently. Only 50% of respondents reported accessing written information about AS, which was obtained mainly in specialist clinics. Women were more likely than men to access information (63% (women) 46% (men)) regardless of the source, while younger patients were more likely to use online sources. The main source of non-written information was the rheumatologist. Overall, the respondents felt there was sufficient information available, but there was a perception that the tone was often too negative. The majority (95%) of people would like to receive a regular newsletter about AS, containing positive practical and local information. Suggestions were also made for more information about AS to be made available to non-specialist medical professionals and the general public.&lt;/p&gt; &lt;p&gt;CONCLUSIONS: There appears to be sufficient information available for people with AS in the UK and this is mostly accessed by younger AS patients. Many patients, particularly men, choose not to access AS information and concerns were raised about its negative tone. Patients still rely on written and verbal information from their specialists. Future initiatives should focus on the delivery of more positive information, targeting younger participants in particular and increasing the awareness in the general population and wider non-specialist medical community.&lt;/p&gt

Metabolomics and microbial composition increase insight into the impact of dietary differences in cirrhosis.

BACKGROUND & AIMS: Dietary changes can modulate gut microbiota and interact with cirrhosis. Our prior study demonstrated that microbial diversity was higher in Turkish versus USA cirrhotics, which was associated with lower risk of 90-day hospitalizations. We aimed to define gut microbial functional and metabolomic changes to increase insight into benefits of the Mediterranean compared to Western diets. METHODS: 139 Turkish (46 controls/50 compensated/43 decompensated) and 157 American subjects (48 controls/59 compensated/50 decompensated) were studied. Turkish subjects consumed a modified Mediterranean diet with daily fermented milk intake while Americans consumed a Western diet. Predicted gut microbial functionalities and plasma metabolomics were compared between/within countries. Correlation network differences between microbiota and metabolites in cirrhotics from Turkey versus USA were evaluated. RESULTS: Predicted microbial function showed lower amino acid, bioenergetics and lipid pathways, with functions related to vitamin B, glycan, xenobiotic metabolism, DNA/RNA synthesis, in Turkey compared to USA cirrhotics. Plasma metabolomics demonstrated higher relative lactate levels in Turkey versus USA. The metabolite changes in decompensated cirrhosis, compared to controls, showed similar trends in Turkey and USA, with reduced lipids and phosphocholines. Phosphocholines were significantly lower in patients hospitalized in 90 days (p=0.03). Correlation networks in cirrhotics demonstrated linkage differences between beneficial taxa, Blautia and Oscillispira, and lactate and unsaturated lipids, in Turkey compared to American patients. CONCLUSIONS: A modified Mediterranean diet was associated with altered plasma metabolomics and beneficially alters microbiota functionality and correlations compared to Western diet in cirrhosis. These altered diet-microbial interactions could potentially affect the 90-day hospitalization risk

Patient perspectives of managing fatigue in ankylosing spondylitis, and views on potential interventions: a qualitative study

&lt;p&gt;Background: Fatigue is a major component of living with ankylosing spondylitis (AS), though it has been largely over-looked, and currently there are no specific agreed management strategies.&lt;/p&gt; &lt;p&gt;Methods: This qualitative exploratory study involved participants who are members of an existing population-based ankylosing spondylitis (PAS) cohort. Participants residing in South West Wales were invited to participate in a focus group to discuss; (1) effects of fatigue, (2) self-management strategies and (3) potential future interventions. The focus groups were audio-recorded and the transcripts were analysed using thematic analysis.&lt;/p&gt; &lt;p&gt;Results: Participants consisted of 3 males/4 females (group 1) and 4 males/3 females (group 2), aged between 35 and 73 years (mean age 53 years). Three main themes were identified: (1) The effects of fatigue were multi-dimensional with participants expressing feelings of being ‘drained’ (physical), ‘upset’ (emotional) and experiencing ‘low-mood’ (psychological); (2) The most commonly reported self-management strategy for fatigue was a balanced combination of activity (exercise) and rest. Medication was reluctantly taken due to side-effects and worries over dependency; (3) Participants expressed a preference for psychological therapies rather than pharmacological for managing fatigue. Information on Mindfulness-Based Stress Reduction (MBSR) was received with interest, with recommendations for delivery in a group format with the option of distance-based delivery for people who were not able to attend a group course.&lt;/p&gt; &lt;p&gt;Conclusions: Patients frequently try and manage their fatigue without any formal guidance or support. Our research indicates there is a need for future research to focus on psychological interventions to address the multi-faceted aspects of fatigue in AS.&lt;/p&gt