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Dossett L.A.,Complex Drive | Kudchadkar R.R.,Emory University | Zager J.S.,Moffitt Cancer Center
Expert Opinion on Drug Safety | Year: 2015

Introduction: Selective inhibition of the MAPK pathway with either BRAF or MEK inhibition has emerged as a key component for the treatment of BRAF-mutant metastatic melanoma. New evidence suggests that the combination of BRAF and MEK inhibitors improves tumor response rate and progression-free survival, while potentially attenuating some of the serious adverse events observed with monotherapy.Areas covered: This review covers the current data on the efficacy and safety of the selective BRAF (vemurafenib and dabrafenib) and MEK (trametinib) inhibitors as well as the available data on BRAF inhibitor + MEK inhibitor combination therapy (dabrafenib + trametinib and vemurafenib + cobimetinib). The efficacy, safety and toxicity data are discussed from Phase I, Phase II and Phase III trials of these drugs.Expert opinion: Combination therapy with the BRAF and MEK inhibitors improves response rates and progression-free survival in patients with BRAF-mutant metastatic melanoma. Some of the serious adverse events, in particular, the incidence of cutaneous squamous cell carcinoma, are attenuated with combination therapy, whereas milder side effects such as pyrexia can be more common with combination therapy. Although dose reductions and dose interruptions are slightly more common with combination therapy, overall data supports the notion that combination therapy is safe and improves the outcomes for patients compared to single agent BRAF inhibitors. © 2015 Informa UK, Ltd. Source


Kumar R.R.,University of The South Pacific | Kumar R.,University of The South Pacific | Kumar R.,Complex Drive
Energy Policy | Year: 2013

The paper investigates the long-run cointegration relationship and energy elasticities for Kenya and South Africa over the periods 1978-2009 and 1971-2009, respectively, using the ARDL procedure developed by Pesaran et al. (2001) with recomputed critical bounds from Narayan (2005) and the Solow (1956) framework extended by Rao (2010). We also conduct the (Toda and Yamamoto (1995) test for Granger non-causality. The regression results show that short-run and long-run energy elasticities are 0.50 and 1.71, respectively for Kenya and 0.17 and 0.34, respectively for South Africa. The causality results indicate a unidirectional Granger causality running from capital per worker and energy per capita to output per worker for both countries. Moreover, in Kenya, we detect a strong unidirectional causality: (a) on output from joint consideration of capital stock and energy; and (b) on capital stock from joint consideration of energy and output. In South Africa, the joint causations are neutral. Hence, while energy and capital stock spurs growth in both countries, Kenya has a greater potential to harness growth and capital productivity via joint consideration of energy with capital and output, respectively. © 2013 Elsevier Ltd. Source


Muallil R.N.,University of the Philippines at Diliman | Muallil R.N.,Mindanao State University | Geronimo R.C.,University of the Philippines at Diliman | Cleland D.,Australian National University | And 5 more authors.
Fisheries Research | Year: 2011

The coastal ecosystems of the Philippines are among the most heavily fished areas in the world. High dependency on fishery resources by an expanding population have resulted in overexploited and deteriorated fish stocks, perpetuating widespread poverty in fishing communities. Reducing fishing pressure through livelihood support provision for fishers could potentially alleviate poverty and mitigate deteriorating fisheries at the same time. However, this requires understanding fishers' behavior toward exiting the fishery and how different socioeconomic factors affect this behavior. We determined fishers' willingness to exit the fishery for different catch and monetary incentive scenarios in 6 coastal towns in the South China Sea biogeographic region of the Philippines. Half the fishers surveyed would continue fishing even when catches fall to 0.5. kg a day. This translates to less than US$1 gross income which is only about 15% of the daily fishers' household expenses in the studied towns. For monetary incentives, 18% of fishers were already willing to exit the fishery at US$111 monthly incentives. This proportion increased to 51% when the offer was increased to US$222 which is about the same as the fishers' monthly household expenses. When the offer was increased to US$333, 18% of fishers still said they would prefer to continue fishing. Fishers who were newer to the fishery and exerting less fishing effort showed more willingness to exit the fishery for both catch and monetary incentive scenarios. Age and educational attainment also influenced fishers' exit decision. These findings demonstrate high heterogeneity in fishers' behavior toward exiting the fishery and that properly targeting those who are more willing to exit the fishery in livelihood programs might both effectively reduce fishing pressure and give fish stocks and other marine ecosystems a chance to recover while improving the fishers' well-being. © 2011 Elsevier B.V. Source


Ritchie S.D.,935 Ramsey Lake Road | Wabano M.J.,Complex Drive | Russell K.,Old Carver 6 MS 9067 | Enosse L.,11A Debajehmujig Lane
Rural and remote health | Year: 2014

Aboriginal people in Canada (First Nations, Inuit and Métis) have a lower health status compared to the Canadian population. There is a particular concern about the mental health and wellbeing of First Nations adolescents living on reserves. Interventions following principles of outdoor education and adventure therapy appear to be an appropriate fit for this population. These approaches have proven effective in non-Aboriginal populations, yet there is very little evidence on the efficacy of these types of program for Aboriginal adolescents. The primary purpose of this study was to evaluate the impact of an outdoor adventure leadership experience (OALE) on the resilience and wellbeing of First Nations adolescents from one reserve community. The secondary purposes were to explore whether this impact was sustainable, and whether there were any intervening factors that may have influenced the impact. The collaborative research team used a mixed-method design to evaluate the 10-day OALE for adolescents from Wikwemikong Unceded Indian Reserve in northern Ontario, Canada. The main outcome assessed was resilience, measured by self-report, using the 14-Item Resilience Scale (RS-14). Several other exploratory measures assessed other aspects of health and well-being. The questionnaire package was administered at three different time periods: (T1) one day before the OALE; (T2) one month after the OALE; and (T3) one year after the OALE. The Mental Component Score (MCS) of the SF-12v2 was used to confirm any changes in resilience. Open-ended questions were appended to the questionnaire at the 1-year point to identify any intervening factors that may have impacted any changes in resilience and wellbeing. The primary analysis compared mean RS-14 scores at T1 with those at T2. Responses to the open-ended questions were analyzed using content analysis. Over two summers (2009 and 2010), 73 youth 12-18 years of age from Wikwemikong participated in a standardized 10-day OALE program. This represented 15% of the on-reserve population of adolescents in this age range. Survey responses from 59 (80.8%) participants were available for analysis at T1, compared to 47 (64.4%) at T2 and 33 (45.2%) at T3. The mean RS-14 score was 73.65 at baseline, and this improved 3.40 points (p=0.011) between T1 and T2. However, the resilience scores at T3 (1 year post-OALE) had a mean of 74.19, indicating a return back to pre-OALE levels. The mean MCS score at T1 was 48.23 and it improved over the subsequent two time periods. Several intervening factors reported at T3 may have influenced the decrease in resilience scores from T2 to T3. These included changes in family living situation, death in the family, and other life stressors that occurred over the course of the year. Outcome scores from this study provide a unique glimpse into the self-reported health and wellbeing for adolescents within one First Nations community in Canada. The OALE program was beneficial in promoting resilience for adolescents in Wikwemikong over the short-term. Future studies are necessary to assess whether the OALE (or similar outdoor type interventions) are effective within other communities. Source


Mateo-Sanchez M.C.,Technical University of Madrid | Balkenhol N.,University of Gottingen | Cushman S.,Complex Drive | Perez T.,University of Oviedo | And 2 more authors.
Landscape Ecology | Year: 2015

Context: Most current methods to assess connectivity begin with landscape resistance maps. The prevailing resistance models are commonly based on expert opinion and, more recently, on a direct transformation of habitat suitability. However, habitat associations are not necessarily accurate indicators of dispersal, and thus may fail as a surrogate of resistance to movement. Genetic data can provide valuable insights in this respect. Objectives: We aim at directly comparing the utility of habitat suitability models for estimating landscape resistance versus other approaches based on actual connectivity data. Methods: We develop a framework to compare landscape resistance models based on (1) a genetic-based multi model optimization and (2) a direct conversion of habitat suitability into landscape resistance. We applied this framework to the endangered brown bear in the Cantabrian Range (NW Spain). Results: We found that the genetic-based optimization produced a resistance model that was more related to species movement than were models produced by direct conversion of habitat suitability. Certain land cover types and transport infrastructures were restrictive factors for species occurrence, but did not appear to impede the brown bear movements that determined observed genetic structure. Conclusions: In this study case, habitat suitability is not synonymous with permeability for dispersal, and does not seem to provide the best way to estimate actual landscape resistance. We highlight the general utility of this comparative approach to provide a comprehensive and practical assessment of factors involved in species movements, with the final aim of improving the initiatives to enhance landscape connectivity in conservation planning. © 2015, Springer Science+Business Media Dordrecht. Source

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