Absence of Respiratory Burst in X-linked Chronic Granulomatous Disease Mice Leads to Abnormalities in Both Host Defense and Inflammatory Response to Aspergillus fumigatus

Mice with X-linked chronic granulomatous disease (CGD) generated by targeted disruption of the gp91phox subunit of the NADPH–oxidase complex (X-CGD mice) were examined for their response to respiratory challenge with Aspergillus fumigatus. This opportunistic fungal pathogen causes infection in CGD patients due to the deficient generation of neutrophil respiratory burst oxidants important for damaging A. fumigatus hyphae. Alveolar macrophages from X-CGD mice were found to kill A. fumigatus conidia in vitro as effectively as alveolar macrophages from wild-type mice. Pulmonary disease in X-CGD mice was observed after administration of doses ranging from 105 to 48 spores, none of which produced disease in wild-type mice. Higher doses produced a rapidly fatal bronchopneumonia in X-CGD mice, whereas progression of disease was slower at lower doses, with development of chronic inflammatory lesions. Marked differences were also observed in the response of X-CGD mice to the administration of sterilized Aspergillus hyphae into the lung. Within 24 hours of administration, X-CGD mice had significantly higher numbers of alveolar neutrophils and increased expression of the proinflammatory cytokines IL-1β and TNF-α relative to the responses seen in wild-type mice. By one week after administration, pulmonary inflammation was resolving in wild-type mice, whereas X-CGD mice developed chronic granulomatous lesions that persisted for at least six weeks. This is the first experimental evidence that chronic inflammation in CGD does not always result from persistent infection, and suggests that the clinical manifestations of this disorder reflect both impaired microbial killing as well as other abnormalities in the inflammatory response in the absence of a respiratory burst

The organisation and delivery of health improvement in general practice and primary care: a scoping study

Background This project examines the organisation and delivery of health improvement activities by and within general practice and the primary health-care team. The project was designed to examine who delivers these interventions, where they are located, what approaches are developed in practices, how individual practices and the primary health-care team organise such public health activities, and how these contribute to health improvement. Our focus was on health promotion and ill-health prevention activities. Aims The aim of this scoping exercise was to identify the current extent of knowledge about the health improvement activities in general practice and the wider primary health-care team. The key objectives were to provide an overview of the range and type of health improvement activities, identify gaps in knowledge and areas for further empirical research. Our specific research objectives were to map the range and type of health improvement activity undertaken by general practice staff and the primary health-care team based within general practice; to scope the literature on health improvement in general practice or undertaken by health-care staff based in general practice and identify gaps in the evidence base; to synthesise the literature and identify effective approaches to the delivery and organisation of health improvement interventions in a general practice setting; and to identify the priority areas for research as defined by those working in general practice. Methods We undertook a comprehensive search of the literature. We followed a staged selection process involving reviews of titles and abstracts. This resulted in the identification of 1140 papers for data extraction, with 658 of these papers selected for inclusion in the review, of which 347 were included in the evidence synthesis. We also undertook 45 individual and two group interviews with primary health-care staff. Findings Many of the research studies reviewed had some details about the type, process or location, or who provided the intervention. Generally, however, little attention is paid in the literature to examining the impact of the organisational context on the way services are delivered or how this affects the effectiveness of health improvement interventions in general practice. We found that the focus of attention is mainly on individual prevention approaches, with practices engaging in both primary and secondary prevention. The range of activities suggests that general practitioners do not take a population approach but focus on individual patients. However, it is clear that many general practitioners see health promotion as an integral part of practice, whether as individual approaches to primary or secondary health improvement or as a practice-based approach to improving the health of their patients. Our key conclusion is that there is currently insufficient good evidence to support many of the health improvement interventions undertaken in general practice and primary care more widely. Future Research Future research on health improvement in general practice and by the primary health-care team needs to move beyond clinical research to include delivery systems and be conducted in a primary care setting. More research needs to examine areas where there are chronic disease burdens – cancer, dementia and other disabilities of old age. Reviews should be commissioned that examine the whole prevention pathway for health problems that are managed within primary care drawing together research from general practice, pharmacy, community engagement, etc

Validating canopy clumping retrieval methods using hemispherical photography in a simulated Eucalypt forest

The so-called clumping factor (Ω) quantifies deviation from a random 3D distribution of material in a vegetation canopy and therefore characterises the spatial distribution of gaps within a canopy. Ω is essential to convert effective Plant or Leaf Area Index into actual LAI or PAI, which has previously been shown to have a significant impact on biophysical parameter retrieval using optical remote sensing techniques in forests, woodlands, and savannas. Here, a simulation framework was applied to assess the performance of existing in situ clumping retrieval methods in a 3D virtual forest canopy, which has a high degree of architectural realism. The virtual canopy was reconstructed using empirical data from a Box Ironbark Eucalypt forest in Eastern Australia. Hemispherical photography (HP) was assessed due to its ubiquity for indirect LAI and structure retrieval. Angular clumping retrieval method performance was evaluated using a range of structural configurations based on varying stem distribution and LAI. The CLX clumping retrieval method (Leblanc et al., 2005) with a segment size of 15° was the best performing clumping method, matching the reference values to within 0.05 Ω on average near zenith. Clumping error increased linearly with zenith angle to > 0.3 Ω (equivalent to a 30% PAI error) at 75° for all structural configurations. At larger zenith angles, PAI errors were found to be around 25–30% on average when derived from the 55–60° zenith angle. Therefore, careful consideration of zenith angle range utilised from HP is recommended. We suggest that plot or site clumping factors should be accompanied by the zenith angle used to derive them from gap size and gap size distribution methods. Furthermore, larger errors and biases were found for HPs captured within 1 m of unrepresentative large tree stems, so these situations should be avoided in practice if possible

Two decades of forest-related legislation changes in European countries analysed from a property rights perspective

In the last two decades, attention on forests and ownership rights has increased in different domains of international policy, particularly in relation to achieving the global sustainable development goals. This paper looks at the changes in forest-specific legislation applicable to regular productive forests, across 28 European countries. We compare the legal framework applicable in the mid-1990s with that applicable in 2015, using the Property Rights Index in Forestry (PRIF) to measure changes across time and space. The paper shows that forest owners in most western European countries already had high decision-making power in the mid-1990s, following deregulation trends from the 1980s; and for the next two decades, distribution of rights remained largely stable. For these countries, the content and direction of changes indicate that the main pressure on forest-focused legislation comes from environmental discourses (e.g. biodiversity and climate change policies). In contrast, former socialist countries in the mid-1990s gave lower decision-making powers to forest owners than in any of the Western Europe countries; over the next 20 years these show remarkable changes in management, exclusion and withdrawal rights. As a result of these changes, there is no longer a clear line between western and former socialist countries with respect to the national governance systems used to address private forest ownership. Nevertheless, with the exception of Baltic countries which have moved towards the western forest governance system, most of the former socialist countries still maintain a state-centred approach in private forest management. Overall, most of the changes we identified in the last two decades across Europe were recorded in the categories of management rights and exclusion rights. These changes reflect the general trend in European forest policies to expand and reinforce the landowners' individual rights, while preserving minimal rights for other categories of forest users; and to promote the use of financial instruments when targeting policy goals related to the environmental discourse

A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1

Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats

Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease

Chagas disease is one of the most important endemic diseases of South and Central America. Its causative agent is the protozoan Trypanosoma cruzi, which is transmitted to humans by blood-feeding insects known as triatomine bugs. These vectors mainly belong to Rhodnius, Triatoma and Panstrongylus genera of Reduviidae. The bacterial communities in the guts of these vectors may have important effects on the biology of T. cruzi. For this reason, we analyzed the bacterial diversity hosted in the gut of different species of triatomines using cultivation-independent methods. Among Rhodnius sp., we observed similar bacterial communities from specimens obtained from insectaries or sylvatic conditions. Endosymbionts of the Arsenophonus genus were preferentially associated with insects of the Panstrongylus and Triatoma genera, whereas the bacterial genus Serratia and Candidatus Rohrkolberia were typical of Rhodnius and Dipetalogaster, respectively. The diversity of the microbiota tended to be the largest in the Triatoma genus, with species of both Arsenophonus and Serratia being detected in T. infestans

Оптимизация конструкции захвата для детали «Барабан»

Грузозахватные приспособления обычно применяются при производстве работ по подъему и перемещению грузов с применением грузоподъемных машин. Использование приспособлений позволяет реализовать максимальное удобство и безопасность производственного процесса. Грузозахватные приспособления конструируются для определенного этапа технологического процесса, для конкретного изделия. При проектировании таких приспособлений необходимо учитывать основные показатели оптимальности конструкции: прочность, надежность, простота, удобство и безопасность при эксплуатации, эргономичность. Кроме того, нужно стремиться к наименьшей массе и, соответственно, металлоемкости захвата. Конструкция грузозахватного приспособления, в основном, будет зависеть от назначенных технологом поверхностей, за которые можно крепиться и от максимальной высоты подъема крюка крана. В статье описана задача по конструированию захвата для детали «Барабан¬ в новом технологическом процессе. Рассмотрена конструкция существующего захвата, взятого за прототип. Приведен анализ различных вариантов конструктивных решений, созданных в процессе проектирования. Выбран вариант конструкции захвата, который в наибольшей степени соответствует требованиям технического задания. Конструкция этого модернизированного приспособления представляет собой захват с тремя лапами, удерживающими деталь, и подвес в виде траверсы. Разработанная конструкторская документация утверждена производством и отделом промышленной безопасности