The UK's Global Health Respiratory Network: Improving respiratory health of the world's poorest through research collaborations.

Respiratory disorders are responsible for considerable morbidity, health care utilisation, societal costs and approximately one in five deaths worldwide [1-4]. Yet, despite this substantial health and societal burden – which particularly affects the world’s poorest populations and as such is a major contributor to global health inequalities – respiratory disorders have historically not received the policy priority they warrant. For example, despite causing an estimated 1000 deaths per day, less than half of the world’s countries collect data on asthma prevalence (http://www.globalasthmareport.org/). This is true for both communicable and non-communicable respiratory disorders, many of which are either amenable to treatment or preventable

Gene profiling of lung toxicity

Bleomycin is a potent anti-tumour compound used in the treatment of squamous cell carcinomas. An unfortunate side effect of this drug is pulmonary toxicity. The onset of this damage manifests as mild oedema and inflammation which eventually develops into pulmonary fibrosis. The ability to correctly identify patients showing early signs of lung injury could significantly reduce the morbidity associated with bleomycin treatment. As such, this study was undertaken to identify genetic markers of early oedema and inflammation. A model of mild pulmonary injury was induced by bleomycin. Conventional quantitative analysis of broncho-alveolar lavage was used to indicate the severity of the oedematous response, whilst morphological changes were identified by histology and electron microscopy. Macroarrays were used to measure the expression of multiple genes during mild, progressive and severe oedema. Following normalisation and statistical analysis, gene expression patterns were compared from saline- and bleomycin-treated rats. A variety of genes were differentially expressed during each model, with the number increasing with the severity of the oedema. A cluster and two individual genes were consistently expressed across two of the models of oedema. The magnitude of the changes in gene expression were quantified and confirmed by quantitative PCR. In summary, complete toxicological and histological characterisation of the bleomycin-induced model of pulmonary injury successfully identified specific endpoints of injury. This model proved to be ideal for studying differential gene expression in response to drug-induced pulmonary oedema. A cluster of ion channels and trafficking genes has the potential to act as a biomarker. Two specific genetic markers (Na+/CI- betaine/GABA transporter, glucocorticoid receptor), and a protein marker (cocoacrisp) have been identified for the oedema. In addition to these genes and protein being potential biomarkers of injury, they are also prospective targets for clinical treatment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Gene profiling of lung toxicity

Bleomycin is a potent anti-tumour compound used in the treatment of squamous cell carcinomas. An unfortunate side effect of this drug is pulmonary toxicity. The onset of this damage manifests as mild oedema and inflammation which eventually develops into pulmonary fibrosis. The ability to correctly identify patients showing early signs of lung injury could significantly reduce the morbidity associated with bleomycin treatment. As such, this study was undertaken to identify genetic markers of early oedema and inflammation. A model of mild pulmonary injury was induced by bleomycin. Conventional quantitative analysis of broncho-alveolar lavage was used to indicate the severity of the oedematous response, whilst morphological changes were identified by histology and electron microscopy. Macroarrays were used to measure the expression of multiple genes during mild, progressive and severe oedema. Following normalisation and statistical analysis, gene expression patterns were compared from saline- and bleomycin-treated rats. A variety of genes were differentially expressed during each model, with the number increasing with the severity of the oedema. A cluster and two individual genes were consistently expressed across two of the models of oedema. The magnitude of the changes in gene expression were quantified and confirmed by quantitative PCR. In summary, complete toxicological and histological characterisation of the bleomycin-induced model of pulmonary injury successfully identified specific endpoints of injury. This model proved to be ideal for studying differential gene expression in response to drug-induced pulmonary oedema. A cluster of ion channels and trafficking genes has the potential to act as a biomarker. Two specific genetic markers (Na+/CI- betaine/GABA transporter, glucocorticoid receptor), and a protein marker (cocoacrisp) have been identified for the oedema. In addition to these genes and protein being potential biomarkers of injury, they are also prospective targets for clinical treatment

Nanotoxicology

As the production and use of nanomaterials (NMs) in medicine and many other applications develops, so the need to understand the potential risks posed by NMs to human health (and the environment) increases (Aitken et al. 2006). At the nanoscale (1-100 nm), materials exhibit properties that are different to larger or bulk materials. These new properties are exploited by researchers and industry to generate new products; however, the same properties can also inuence how the NM behaves in biological systems, including affecting toxicity. Nanotoxicology is a relatively new eld of research that aims to assess the human and environmental hazard of nanomaterials. In recent years, this new discipline has seen a rapid expansion in the number of studies concerned with assessing the safety of engineered NMs (Figure 20.1)

Potestad dictaminadora de la Contraloría General de la República

Memoria (licenciado en ciencias jurídicas y sociales)El 18 de septiembre del año 2010 nuestro país celebró doscientos años desde que comenzara el proceso de independencia que conduciría al establecimiento de la República de Chile. Como enseña la historiografía actual, los movimientos americanos que conllevaron el colapso del sistema imperial español se enmarcan dentro de los procesos históricos mayores que configuran la era de las revoluciones. Hasta finales del siglo XVIII y comienzos del XIX, el poder político dimanaba directamente de la persona del soberano – rey o emperador en su caso – y los habitantes de los reinos fueron durante el ancièn règime llamados súbditos. Fue recién el 14 de julio de 1789, cuando las barriadas parisinas se amotinaron contra el poder despótico de su monarca, que los súbditos pasaron a llamarse ciudadanos. El sistema que surgiría de las cenizas del parto sangriento de la modernidad se caracterizaría por promover una radical separación de los poderes y elestablecimiento de la ley como baluarte supremo de las libertades individuales del ciudadano. Esta idea de que la ley es el origen, fundamento y límite del actuar del poder público es lo que en Derecho se ha denominado principio de legalidad. Así, el destacado administrativista español García de Enterría nos enseña: “Una vez que esa nueva concepción de Derecho (en su fuente; en su manifestación, en su fin) se ha consolidado, el concepto de Estado de Derecho se identifica con su realización y se erige en un modelo de Derecho Natural que va a presidir toda la evolución política de Occidente hasta nuestros días. Hoy se mantiene, y aun se acendra, la misma convicción común sobre el origen y el fin del Derecho; la radical igualdad de los hombres, a la que la conciencia actual es especialmente sensible, la impone, de modo que cualquier otro sistema básico de Derecho que parte necesariamente de la negación de esa igualdad (en beneficio de un hombre, o de un grupo, o de una clase, o de un partido, o de una iglesia), y del sometimiento de los ciudadanos a fines y a mitos transpersonales, que exceden siempre necesariamente de su propio bien y lo instrumentalizan. El segundo elemento estructural, referente a la necesaria producción del Derecho por medio de leyes generales, ha sido, sin embargo, erosionando, quizás paralelamente a la transformación de la ley natural en la concepción del propio mundo físicos y biológico y, como ya hemos visto más atrás, no hay ningún inconveniente de principio en la admisión de leyes singulares, que hoy son, además, perfectamente normales en todos los ordenamientos (sin perjuicio de que no sean ya, o al menos no deban ser, los rescriptos singulares o lettres de cachet del absolutismo, excepciones arbitrarias al sistema general de los derechos) . El principio de legalidad es precisamente lo que dota de contenido a la expresión “Estado de Derecho”. Innumerables definiciones se han dado de este concepto tantas veces invocado, pero en general nos refiere a la idea de racionalización del ejercicio del poder político por medio del principio de legalidad

Combustion-derived nanoparticles: mechanisms of pulmonary toxicity

1. The general term ‘nanoparticle’ (NP) is used to define any particle less than 100 nm in at least one dimension and NPs are generally classified as natural, anthropogenic or engineered in origin. Anthropogenic, also referred to as ‘ultrafine’ particles (UFPs), are predominately combustion derived and are characterized by having an equivalent spherical diameter less than 100 nm. 2. These particles, considered to be ‘combustion-derived nanoparticles’ (CDNPs), are of toxicological interest given their nanosized dimensions, with properties not displayed by their macroscopic counterparts. 3. The pulmonary deposition efficiency of inhaled UFPs, along with their large surface areas and bound transition metals, is considered important in driving the emerging health effects linked to respiratory toxicity. 4. The toxicology of CDNPs is currently used to predict the health outcomes in humans following exposure to manufactured NPs. Their similar physicochemistry would suggest similar adverse health effects (i.e. pulmonary (and perhaps cardiac) toxicity). As such, it is essential to fully understand CDNP nanotoxicology in order to minimize occupational and environmental exposure. Key words: carbon black, combustion-derived particles, diesel exhaust, fly ash, nanoparticles, pulmonary toxicity

Mapping national information and communication technology (ICT) infrastructure to the requirements of potential digital health interventions in low- and middle-income countries

Background Digital health can support health care in low- and middle-income countries (LMICs) by overcoming problems of distance, poor infrastructure and the need to provide community practitioners with specialist support. We used five RESPIRE countries as exemplars (Bangladesh, India, Indonesia, Malaysia, Pakistan) to identify the digital health solutions that are valuable in their local setting, worked together with local clinicians and researchers to explore digital health policy, electricity/ICT infrastructure, and socio-cultural factors influencing users’ ability to access, adopt and utilise digital health. Methods We adopted the Joanna Briggs Institute’s scoping review protocol and followed the Cochrane Rapid Review method to accelerate the review process, using the Implementation and Operation of Mobile Health projects framework and The Extended Technology Acceptance Model of Mobile Telephony to categorise the results. We conducted the review in four stages: (1) establishing value, (2) identifying digital health policy, (3) searching for evidence of infrastructure, design, and end-user adoption, (4) local input to interpret relevance and adoption factors. We used open-source national/international statistics such as the World Health Organization, International Telecommunication Union, Groupe Speciale Mobile, and local news/articles/government statistics to scope the current status, and systematically searched five databases for locally relevant exemplars. Results We found 118 studies (2015-2021) and 114 supplementary online news articles and national statistics. Digital health policy was available in all countries, but scarce skilled labour, lack of legislation/interoperability support, and interrupted electricity and internet services were limitations. Older patients, women and those living in rural areas were least likely to have access to ICT infrastructure. Renewable energy has potential in enabling digital health care. Low usage mobile data and voice service packages are relatively affordable options for mHealth in the five countries. Conclusions Effective implementation of digital health technologies requires a supportive policy, stable electricity infrastructures, affordable mobile internet service, and good understanding of the socio-economic context in order to tailor the intervention such that it functional, accessible, feasible, user-friendly and trusted by the target users. We suggest a checklist of contextual factors that developers of digital health initiatives in LMICs should consider at an early stage in the development process

ITS-NANO - Prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy

Background To assess the risk of all nanomaterials (NMs) on a case-by-case basis is challenging in terms of financial, ethical and time resources. Instead a more intelligent approach to knowledge gain and risk assessment is required. Methods A framework of future research priorities was developed from the accorded opinion of experts covering all major stake holder groups (government, industry, academia, funders and NGOs). It recognises and stresses the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling approaches as key components of the current and future risk assessment of NMs. Results The framework for future research has been developed from the opinions of over 80 stakeholders, that describes the research priorities for effective development of an intelligent testing strategy (ITS) to allow risk evaluation of NMs. In this context, an ITS is a process that allows the risks of NMs to be assessed accurately, effectively and efficiently, thereby reducing the need to test NMs on a case-by-case basis. For each of the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling, key-priority research areas are described via a series of stepping stones, or hexagon diagrams structured into a time perspective. Importantly, this framework is flexible, allowing individual stakeholders to identify where their own activities and expertise are positioned within the prioritisation pathway and furthermore to identify how they can effectively contribute and structure their work accordingly. In other words, the prioritisation hexagon diagrams provide a tool that individual stakeholders can adapt to meet their own particular needs and to deliver an ITS for NMs risk assessment. Such an approach would, over time, reduce the need for testing by increasing the reliability and sophistication of in silico approaches. The manuscript includes an appraisal of how this framework relates to the current risk assessment approaches and how future risk assessment could adapt to accommodate these new approaches. A full report is available in electronic format (pdf) at http://www.nano.hw.ac.uk/research-projects/itsnano.html webcite. Conclusion ITS-NANO has delivered a detailed, stakeholder driven and flexible research prioritisation (or strategy) tool, which identifies specific research needs, suggests connections between areas, and frames this in a time-perspective

Rewilding as a restoration strategy for lowland agricultural landscapes: Stakeholder-assisted multi-criteria analysis in Dorset, UK

© 2018 Elsevier GmbH The ongoing loss of global biodiversity suggests that established conservation practices have not been fully successful at halting species decline. Rewilding, a restoration strategy focused on restoring ecological processes, has become increasingly prominent as a potential means of addressing this problem. Rewilding has been described as a versatile approach that is applicable even in areas with dense human populations and productive agricultural landscapes such as the lowlands of Western Europe. Yet little is known about the options that might exist for rewilding such landscapes, or about their relative suitability. The present study addresses this knowledge gap by assessing the relative popularity and suitability of different rewilding scenarios in the county of Dorset, south-west England, involving the consultation of local stakeholders. Survey results showed strong support for rewilding among stakeholders, with the reintroduction of beavers (Castor fiber) and pine martens (Martes martes) being especially popular. Yet stakeholder perceptions also differed regarding how rewilding should be defined, and what it comprises. The suitability of the proposed rewilding approaches was measured through a spatial multi-criteria analysis using the following variables: popularity among stakeholders, suitability within relevant land cover types, and suitability at the landscape-scale. Naturalistic grazing and farmland abandonment emerged as the most suitable rewilding options overall, although these were not the most popular choices. Overall, these results suggest that land managers in lowland agricultural landscapes could consider rewilding as one of the land management options available to them, provided that the options being considered are ecologically appropriate and local stakeholders have been consulted. In the UK, such rewilding options might be supported by new national agricultural land use policies currently under development. In areas of continental Europe where agricultural land abandonment is more widespread, policy-makers seeking to address the issue could look towards the EU's wilderness guidelines for potential solutions that promote rewilding while offsetting the costs incurred by local stakeholders. In either context, integrated exploration of stakeholder values and ecological data as presented here can potentially be used to evaluate the relative suitability and popularity of different rewilding approaches, and thereby establish priorities