Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone

Advances in reproductive biology and seed production systems of Eucalyptus: The case of Eucalyptus globulus

Eucalyptus globulus is the main eucalypt species grown in Australian plantations. The focus on seedling deployment systems, coupled with exploitation of large, open-pollinated base populations for breeding purposes over the last two decades, has required a detailed understanding of the reproductive biology of this species. We review our research on the reproductive biology of E. globulus, with a focus on it’s breeding system and advances made in seed production systems. While most improved seed is still obtained from open-pollinated seedling or grafted seed orchards, the development of the one-stop/single-visit pollination procedure has revolutionised the breeding and deployment of this species. The reduced costs of controlled pollination has meant full pedigree-control can now be maintained in large advanced generation breeding populations and E. globulus is one of the few eucalypt species where large-scale production of manually pollinated seed for family forestry is being undertaken

Phenological tracking of a seasonal climate window in a recovering tropical island bird species

Constraints on evolutionary adaptation and range shifts mean that phenotypic plasticity, which includes physiological, developmental or behavioural responses to environmental conditions, could be an important mode of adaptation to a changing climate for many species with small insular populations. While there is evidence to suggest adaptive plasticity to climate in some island populations, little is known about this capacity in species that have experienced a severe population bottleneck. In a changing climate, plasticity in the timing of life-history events, such as in breeding phenology, is adaptive if timing is optimised in seasonal environments, although these processes are poorly understood for tropical species. Here, we quantify the effects of climate on the breeding phenology and success of the Mauritius kestrel (Falco punctatus), a tropical raptor whose extinction has been averted by conservation management. We show that the timing of egg-laying is advancing in response to warming, at rates similar to temperate bird populations. Individual females show plasticity to temperature, although there is limited variation among individual responses. We show that advances in breeding phenology are likely to be adaptive, as they track changes in a seasonal climate window of favourable conditions, defined by late winter-early spring temperatures and the onset of the summer rainy season. Our results provide a rare example of a small and bottlenecked insular population that has adjusted to recent climate change through phenotypic plasticity. Furthermore, seasonal climate windows and their dynamics may be widespread mechanisms through which tropical species are impacted by and respond to climate change

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

Exploring Entrepreneurial Skills and Competencies in Farm Tourism

Diversification to farm tourism is increasingly seen as a viable development strategy to promote a more diverse and sustainable rural economy and to counter declining farm incomes. However, our understanding of the dynamics of the modern farm tourism business and the entrepreneurial and competitive skills farmers require in making the transition from agriculture to a diversified - and service based - enterprise remains limited. Hence, the aim of this paper is to explore the range of skills and competencies that farmers in the North West of England identify as important when adopting a diversification strategy to farm tourism. With the findings indicating that that whilst a range of managerial skills are valued by farmers, they lack many of the additional business and entrepreneurial competencies required for success. Moreover, this paper acknowledges the need to generate consensus on the requisite skill-set that farm tourism operators require, along with a need for a currently fragmented rural tourism literature to acknowledge the significance of rural entrepreneurship and the characteristics of successful farmers and farm tourism ventures

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

Access to interpreting services in England: secondary analysis of national data

Background: Overcoming language barriers to health care is a global challenge. There is great linguistic diversity in the major cities in the UK with more than 300 languages, excluding dialects, spoken by children in London alone. However, there is dearth of data on the number of non-English speakers for planning effective interpreting services. The aim was to estimate the number of people requiring language support amongst the minority ethnic communities in England. Methods: Secondary analysis of national representative sample of subjects recruited to the Health Surveys for England 1999 and 2004. Results: 298,432 individuals from the four main minority ethnic communities (Indian, Pakistani, Bangladeshi and Chinese) who may be unable to communicate effectively with a health professional. This represents 2,520,885 general practice consultations per year where interpreting services might be required. Conclusion: Effective interpreting services are required to improve access and health outcomes of non-English speakers and thereby facilitate a reduction in health inequalities

Estradiol and testosterone levels in patients undergoing partial hepatectomy - A possible signal for hepatic regeneration?

In five adult male patients undergoing a 40-60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40-60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection. © 1989 Plenum Publishing Corporation