Evaluation of an educational programme for socially deprived asthma patients

The aim of this study was to evaluate the effectiveness of an asthma education programme in moderate and severe asthma patients in a longitudinal, prospective and randomized study with a control group. Fifty-three asthmatic patients were studied, 26 of whom were assigned to the educational group and 27 to the control group.The educational group attended the programme regularly for a period of 6 months. the programme included information about asthma, instruction on the appropriate use of medication and training in the metered dose inhaler (MDI) technique, and information about the identification and control of asthma attacks and the recognition of early signs of exacerbation. the control group was submitted to the routine tare provided at the Asthma Clinic, with no formal instruction regarding asthma control. the groups were identical with regard to severity parameters, skills, lung function and quality of Life at the beginning of the trial.At the end of the study, the education group showed significant differences when compared with the control group education/control (mean values) with respect to: visits to the asthma emergency room over the previous 6 months, 0.7/2 (p=0.03); nocturnal symptoms, 0.3/0.7 (p=0.04); score of symptoms, 1.3/2 (p=0.04). Improvements were also observed in skills and quality of life, knowledge of how to deal with attacks and how to control the environmental triggering factors, 73/35 (<0.05); correct use of the MDI, 8/4 (0.001); understanding of the difference between relief and antiinflammatory medication, 86/20 (<0.05); and in the global limitation quality of life score, 28/50 (0.02).It is concluded that the educational programme led to a significant improvement in asthma morbidity and that the implantation of educational programmes is possible for special populations when these programmes are adapted to the socioeconomic profile of the patients, with a significant gain in terms of the reduction of symptoms and improved pulmonary function and quality of life of asthmatics.Universidade Federal de São Paulo, Dept Med, Lund Div, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Lund Div, São Paulo, BrazilWeb of Scienc

Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration

Genetic and Observational Subarachnoid Haemorrhage (GOSH) Study - A UK-wide clinical and genetic cohort study of aneurysmal subarachnoid haemorrhage

Introduction: Intracranial aneurysms affect 2-5% of the general population.1 A tiny proportion of these rupture leading to aneurysmal subarachnoid haemorrhage (SAH), which can be fatal instantly or lead to life-changing neurological morbidity in a young group of stroke survivors. Understanding the pathophysiological mechanisms underlying intracranial aneurysms, and being able to predict which patients have a higher risk of rupture has led to intensive research efforts, via epidemiological, molecular and genetic studies. Our aim was to determine the association of candidate genes with intracranial aneurysms in a large UK Caucasian population. Methods: We performed a case-control genetic association study of single nucleotide polymorphisms (SNPs) in over 1600 patients with intracranial aneurysms from a UK-wide Genetic and Observational Subarachnoid Haemorrhage (GOSH) study and 1500 controls from the Wellcome cohort,2 utilising a candidate-gene approach. We conducted a literature review and performed a meta-analysis of the existing candidate gene studies to better determine which genes would be suitable for analysis in our cohort. We also performed a new meta-analysis using our data for each SNP examined to determine if our genetic associations with intracranial aneurysms were robust. Results: We examined 22 SNPs related to vascular endothelial integrity, the extracellular matrix, and inflammation. Two SNPs showed associations with intracranial aneurysms in our UK cohort: the D allele of ACE Insertion/Deletion SNP (associated with vascular endothelial function; OR 1.14 [1.02-1.28], p=0.02) and the MMP-2 C>T rs243865 SNP (associated with extracellular matrix integrity; OR 1.18 [1.04 – 1.33], p=0.012). Conclusions: We found associations with intracranial aneurysms for the D allele of the ACE I/D SNP, and a potentially functionally significant MMP-2 SNP. Both genes have plausible connections to IA pathophysiology (endothelial function and extracellular matrix integrity, respectively), and could potentially predispose patient to aneurysm rupture as demonstrated by sub-group analysis

Business Improvement Districts in England and the (private?) governance of urban spaces

Business Improvement Districts (BIDs) were introduced in England just over ten years ago, and their adoption in over 180 locations all over the country owes a great deal to their potential ability to raise private funds to invest in the development of business areas. However, much of the academic literature on BIDs has been critical of what it sees as an expansion of corporate control of urban spaces and the weakening of elected local government, often on the evidence of a long-running North American debate. On the basis of ten case studies of English BIDs, in this paper I address the evolution of those organisations as private stakeholder-led instruments for the governance and management of business areas in England. I discuss whether and to what extent English BIDs constitute private government of urban areas, and the attendant issues of accountability and spatial inequalities in the distribution of public services and investment. I conclude by examining the implications of its findings for the future of urban governance

Deformation-Induced Electric Currents in Marble Under Simulated Crustal Conditions: Non-Extensivity, Superstatistical Dynamics and Implications for Earthquake Hazard

This thesis investigates electric current signals generated spontaneously in specimens of Carrara marble during deformation under crustal conditions. It extends previous work where similar currents were observed during uniaxial deformation of marble. Since marble is a non-piezoelectric material, one of the main questions is how these currents are related to the mechanical processes of deformation. Another question is whether it is possible to extract from these electric currents information about the deformation dynamics. This is particularly important in light of recent claims that geoelectric anomalies observed in the field are related to crustal deformation and can inform us about changes in the organisation of the fault network in a focal region prior to an earthquake. Using an approach that combines rock deformation experiments and statistical modelling, I examine how these electric currents evolve with deformation at the laboratory scale and make several original discoveries regarding their behaviour. To establish how the current signals varied with experimental condition and deformation mechanism across the brittle-ductile transition, I conducted constant strain rate triaxial compression experiments recording differential electric current flow through the rock samples at various confining pressures, strain rates and pore fluid conditions. I acquired mechanical data, ultrasonic velocities and acoustic emissions simultaneously, along with electric current, to constrain the relationship between electric current and deformation. For the statistical modelling, I used a novel entropy-based model, derived from non-extensive statistical mechanics (Tsallis, 1988), which has the advantage of including a term to account for interactions in the system. Interactions are effectively modelled by the non-extensive q-parameter. Small (nanoAmpere) electric currents are generated and sustained during deformation under all the conditions tested. Spontaneous electric current flow in the dry samples is seen only in the region of permanent deformation and is due to the presence of localised electric dipoles. This current flow is correlated to the damage induced by microcracking, with a contribution from other intermittent ductile mechanisms. Current and charge densities are consistent with proposed models of crack separation charging and migrating charged edge dislocations. The onset of current flow occurs only after a 10% reduction in P-wave velocity, implying that some degree of crack damage and/or crack connectivity is required before current will flow through the samples. Electric current evolution exhibits three separate time-scales of behaviour, the absolute and fluctuating components of which can be related to the evolution of stress, deformation mechanism, damage and localisation of deformation leading up to sample failure. In the brittle regime, electric current exhibits a precursory change as the stress drop accelerates towards failure, which is particularly distinct at dynamic strain rates. Current and charge production depend strongly on the experimental conditions. Power-law relationships are seen with confining pressure and strain rate, with the first corresponding to increased microcrack suppression and the second to time-dependent differences in deformation mechanism across the brittle-ductile transition. In the presence of an ionic pore fluid, electrokinetic effects dominate over solid-state mechanisms but development of the crack network and charge contribution from solid-state deformation processes drive the variation in electrokinetic parameters. Current flow in the dry samples is approximately proportional to stress within 90% of peak stress. In the fluid-saturated samples, proportionality holds from 40% peak stress, with a significant increase in the rate of current production from 90% peak stress, and is associated with fluid flow during dilatancy. This proportionality, together with the power-law relationship between current and strain rate is reminiscent of power-law creep, where deformation rate varies as a power-law function of stress, and suggests that the electric signals could be used as a proxy for stress. High frequency fluctuations in the electric current signal can be described by `fat-tailed' q-Gaussian statistics, consistent with an origin in non-extensive statistical mechanics. These distributions can be explained as arising from superstatistical dynamics (Beck, 2001; Beck and Cohen, 2003), i.e., the superposition of local mechanical relaxations in the presence of a slowly varying driving force. The macroscopic distribution parameters provide an excellent prediction of the experimentally observed mean energy dissipation rate of the system (as modelled by the superstatistical β-parameter), particularly at slow strain rates. Furthermore, characteristic q-values are obtained for different deformation regimes across the brittle-ductile transition, and the evolution of q during deformation reveals a two-stage precursory anomaly prior to sample failure, consistent with the stress intensity evolution as modelled from fracture mechanics. These findings indicate that the dynamics of rock deformation are reflected in the statistical properties of the recorded electric current. My findings support the notion that electric currents in the crust can be generated purely from deformation processes themselves. Scaling up the laboratory results to large stressed rock volumes at shallow crustal pressures and constant crustal strain rates, deformation induced transient telluric current systems may be as large as 1 MA, even accounting for >99% dissipation, which corresponds to a huge accumulated net charge of 10 ZC. This implies that a significant amount of charge from deforming tectonic regions contributes to the Earth's telluric currents and electric field, although due to conduction away from the stressed rock volume, it is unlikely that accumulated charge of this quantity would ever be measured in the field. Electric current evolution and its precursory characteristics can be related to models for electric earthquake precursors and fault-zone damage organisation, developed from field observations, providing experimental support for them. However, given the oscillatory nature of the current evolution observed during cataclastic flow processes in the laboratory, there is a high probability of false alarms. Furthermore, the potential for electric anomalies to be useful as earthquake precursors remains contentious due to the difficulties of separating deformation-induced signals from other telluric noise and the wider issue of establishing a statistically significant link with earthquakes

Mechanisms and treatment of ischaemic stroke: insights from genetic associations

The precise pathophysiology of ischaemic stroke is unclear, and a greater understanding of the different mechanisms that underlie large-artery, cardioembolic and lacunar ischaemic stroke subtypes would enable the development of more-effective, subtype-specific therapies. Genome-wide association studies (GWASs) are identifying novel genetic variants that associate with the risk of stroke. These associations provide insight into the pathophysiological mechanisms, and present opportunities for novel therapeutic approaches. In this Review, we summarize the genetic variants that have been linked to ischaemic stroke in GWASs to date and discuss the implications of these associations for both our understanding and treatment of ischaemic stroke. The majority of genetic variants identified are associated with specific subtypes of ischaemic stroke, implying that these subtypes have distinct genetic architectures and pathophysiological mechanisms. The findings from the GWASs highlight the need to consider whether therapies should be subtype-specific. Further GWASs that include large cohorts are likely to provide further insights, and emerging technologies will complement and build on the GWAS findings

Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals.

There is an urgent need to identify risk factors for sporadic intracranial aneurysm (IA) development and rupture. A genetic component has long been recognized, but firm conclusions have been elusive given the generally small sample sizes and lack of replication. Genome-wide association studies have overcome some limitations, but the number of robust genetic risk factors for IA remains uncertain