Coupling of pollination services and coffee suitability under climate change

Climate change will cause geographic range shifts for pollinators and major crops, with global implications for food security and rural livelihoods. However, little is known about the potential for coupled impacts of climate change on pollinators and crops. Coffee production exemplifies this issue, because large losses in areas suitable for coffee production have been projected due to climate change and because coffee production is dependent on bee pollination. We modeled the potential distributions of coffee and coffee pollinators under current and future climates in Latin America to understand whether future coffee-suitable areas will also be suitable for pollinators. Our results suggest that coffee-suitable areas will be reduced 73–88% by 2050 across warming scenarios, a decline 46–76% greater than estimated by global assessments. Mean bee richness will decline 8–18% within future coffee-suitable areas, but all are predicted to contain at least 5 bee species, and 46–59% of future coffee-suitable areas will contain 10 or more species. In our models, coffee suitability and bee richness each increase (i.e., positive coupling) in 10–22% of future coffee-suitable areas. Diminished coffee suitability and bee richness (i.e., negative coupling), however, occur in 34–51% of other areas. Finally, in 31–33% of the future coffee distribution areas, bee richness decreases and coffee suitability increases. Assessing coupled effects of climate change on crop suitability and pollination can help target appropriate management practices, including forest conservation, shade adjustment, crop rotation, or status quo, in different regions

Targeted inhibitors and antibody immunotherapies: Novel therapies for paediatric leukaemia and lymphoma

Despite improved outcomes achieved in the last decades for children with newly diagnosed leukaemia and lymphoma, treatment of patients with refractory/relapsed disease remains a challenge. The cure rate is still unsatisfactory and often achieved at the cost of significant morbidity. Exploring treatment with novel agents should offer less toxic therapeutic options, without compromising efficacy. Bispecific and antibody-drug conjugates targeting CD19 and CD22 (blinatumomab and inotuzumab ozogamicin) play an important role in the treatment of relapsed and refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL); antibodies targeting CD123 and CD38 are also under investigation for acute myeloid leukaemia (AML) and T-ALL, respectively. Targeted therapy with small molecules is of primary importance for specific genetic subtypes, such as BCR-ABL-positive ALL, FLT3-ITD AML and anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. KMT2A-directed targeted therapy with menin inhibitors holds promise to be of relevance in KMT2A-rearranged leukaemias, known to have dismal prognosis. Target inhibition in cellular pathways such as BCL-2, RAS, MEK, Bruton's tyrosine kinase, JAK-STAT or CDK4/CDK6 inhibition may be suitable for different diseases with common mutated pathways. Nevertheless, development and approval of new agents for paediatric cancers lags behind adult therapeutic options. New regulations were implemented to accelerate drug development for children. Considering the number of oncology medicinal products available for adults and the rarity of paediatric cancers, prioritisation based on scientific evidence and medical need, as well as international collaboration, is critical. Herein, we review the current status of drug development for children with leukaemia and lymphoma, excluding cellular therapy despite its well-known significance

Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

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Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies

The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile.

The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course

Alcohol mixed with energy drink (AMED): A critical review and meta-analysis

© 2018 The Authors Human Psychopharmacology: Clinical and Experimental Published by John Wiley & Sons Ltd. The purpose of this systematic review and meta-analysis was to critically review the (1) prevalence of alcohol mixed with energy drink (AMED) consumption, (2) motives for AMED consumption, (3) correlates of AMED consumption, and (4) whether AMED consumption has an impact on (a) alcohol consumption, (b) subjective intoxication, and (c) risk-taking behavior. Overall a minority of the population consumes AMED, typically infrequently. Motives for AMED consumption are predominantly hedonistic and social. Meta-analyses revealed that AMED consumers drink significantly more alcohol than alcohol-only (AO) consumers. Within-subject comparisons restricted to AMED consumers revealed that alcohol consumption does not significantly differ between typical AMED and AO occasions. On past month heaviest drinking occasions, AMED users consume significantly less alcohol on AMED occasions when compared to AO occasions. AMED consumers experience significantly fewer negative consequences and risk-taking behavior on AMED occasions compared with AO occasions. Meta-analyses of subjective intoxication studies suggest that AMED consumption does not differentially affect subjective intoxication when compared to AO consumption. In conclusion, when compared to AO consumption, mixing alcohol with energy drink does not affect subjective intoxication and seems unlikely to increase total alcohol consumption, associated risk-taking behavior, nor other negative alcohol-related consequences. Further research may be necessary to fully reveal the effects of AMED

An integrative research framework for enabling transformative adaptation

Transformative adaptation will be increasingly important to effectively address the impacts of climate change and other global drivers on social-ecological systems. Enabling transformative adaptation requires new ways to evaluate and adaptively manage trade-offs between maintaining desirable aspects of current social-ecological systems and adapting to major biophysical changes to those systems. We outline such an approach, based on three elements developed by the Transformative Adaptation Research Alliance (TARA): (1) the benefits of adaptation services; that sub-set of ecosystem services that help people adapt to environmental change; (2) The values-rules-knowledge perspective (vrk) for identifying those aspects of societal decision-making contexts that enable or constrain adaptation and (3) the adaptation pathways approach for implementing adaptation, that builds on and integrates adaptation services and the vrk perspective. Together, these elements provide a future-oriented approach to evaluation and use of ecosystem services, a dynamic, grounded understanding of governance and decision-making and a logical, sequential approach that connects decisions over time. The TARA approach represents a means for achieving changes in institutions and governance needed to support transformative adaptationThe research was supported by CSIRO Land and Water. We thank the Embassy of France in Australia and the Australian Academy of Sciences for funding the first Transformative Adaptation Research Alliance workshop in Canberra, October 27-31, 2014. We thank Craig Beatty, Mirjam Kuzee (IUCN) and Alistair Hobday (CSIRO Oceans and Atmosphere) for reviewing the manuscript and providing constructive comments. The funding partners that have supported this research include the International Climate Initiative (IKI) of the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the CGIAR Research Program on Forests, Trees and Agroforestry (CRP-FTA) with financial support from the CGIAR Fun

t4 Workshop Report: Integrated Testing Strategies (ITS) for Safety Assessment

Integrated testing strategies (ITS), as opposed to single definitive tests or fixed batteries of tests, are expected to efficiently combine different information sources in a quantifiable fashion to satisfy an information need, in this case for regulatory safety assessments. With increasing awareness of the limitations of each individual tool and the development of highly targeted tests and predictions, the need for combining pieces of evidence increases. The discussions that took place during this workshop, which brought together a group of experts coming from different related areas, illustrate the current state of the art of ITS, as well as promising developments and identifiable challenges. The case of skin sensitization was taken as an example to understand how possible ITS can be constructed, optimized and validated. This will require embracing and developing new concepts such as adverse outcome pathways (AOP), advanced statistical learning algorithms and machine learning, mechanistic validation and “Good ITS Practices”.JRC.I.5-Systems Toxicolog