Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Decomposition analysis on soybean productivity increase under elevated CO2 using 3-D canopy model reveals synergestic effects of CO2 and light in photosynthesis.

BACKGROUND AND AIMS: Understanding how climate change influences crop productivity helps in identifying new options to increase crop productivity. Soybean is the most important dicotyledonous seed crop in terms of planting area. Although the impacts of elevated atmospheric [CO2] on soybean physiology, growth and biomass accumulation have been studied extensively, the contribution of different factors to changes in season-long whole crop photosynthetic CO2 uptake [gross primary productivity (GPP)] under elevated [CO2] have not been fully quantified. METHODS: A 3-D canopy model combining canopy 3-D architecture, ray tracing and leaf photosynthesis was built to: (1) study the impacts of elevated [CO2] on soybean GPP across a whole growing season; (2) dissect the contribution of different factors to changes in GPP; and (3) determine the extent, if any, of synergism between [CO2] and light on changes in GPP. The model was parameterized from measurements of leaf physiology and canopy architectural parameters at the soybean Free Air CO2 Enrichment (SoyFACE) facility in Champaign, Illinois. KEY RESULTS: Using this model, we showed that both a CO2 fertilization effect and changes in canopy architecture contributed to the large increase in GPP while acclimation in photosynthetic physiological parameters to elevated [CO2] and altered leaf temperature played only a minor role in the changes in GPP. Furthermore, at early developmental stages, elevated [CO2] increased leaf area index which led to increased canopy light absorption and canopy photosynthesis. At later developmental stages, on days with high ambient light levels, the proportion of leaves in a canopy limited by Rubisco carboxylation increased from 12.2 % to 35.6 %, which led to a greater enhancement of elevated [CO2] to GPP. CONCLUSIONS: This study develops a new method to dissect the contribution of different factors to responses of crops under climate change. We showed that there is a synergestic effect of CO2 and light on crop growth under elevated CO2 conditions.

Identifying strategies to improve diabetes care in Alberta, Canada, using the knowledge-to-action cycle.

BACKGROUND: Strategic clinical networks, a recent development in the health system in Alberta, have been charged with bringing together front-line clinicians, researchers and policy-makers to identify variation in clinical care, and to propose standards, pathways and innovative solutions to improve access and quality of care. Here, we describe a collaborative workshop held between researchers and the Obesity, Diabetes and Nutrition Strategic Clinical Network to describe barriers to and facilitators of care for people with diabetes and to identify quality improvement interventions that should be prioritized. METHODS: Through collaboration between health researchers and the strategic clinical network, and using principles of the knowledge-to-action cycle, we identified barriers to and facilitators of diabetes care using data from a patient survey and a provider focus group (5 primary care physicians and 1 diabetes educator). In addition, we identified best evidence from a systematic review of quality improvement initiatives in diabetes. This information was reviewed at a multistakeholder workshop where potential quality improvement initiatives were considered at various service levels. RESULTS: A pilot survey involving 59 patients with diabetes and a focus group of primary care and allied health care providers identified several important barriers to optimal outcomes in diabetes care, including patient-level financial barriers to care and difficulty navigating the health system. Our collaborative discussion using the knowledge-to-action cycle prioritized feasible, evidence-based interventions to improve outcomes for patients with diabetes, including enabling care by allied health care providers and creating clear care maps and processes for system navigation. INTERPRETATION: We identified important barriers to achieving optimal outcomes in diabetes that may be overcome through the use of evidence-based quality improvement interventions. As recommended within the knowledge-to-action cycle, future research is required to determine whether program implementation improves outcomes and is cost-effective.

Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin.

Thrombin is a multifunctional protease that plays a key role in hemostasis, thrombosis, and inflammation. Most thrombin inhibitors currently used as antithrombotic agents target thrombin's active site and inhibit all of its myriad of activities. Exosites 1 and 2 are distinct regions on the surface of thrombin that provide specificity to its proteolytic activity by mediating binding to substrates, receptors, and cofactors. Exosite 1 mediates binding and cleavage of fibrinogen, proteolytically activated receptors, and some coagulation factors, while exosite 2 mediates binding to heparin and to platelet receptor GPIb-IX-V. The crystal structures of two nucleic acid ligands bound to thrombin have been solved. Previously Padmanabhan and colleagues solved the structure of a DNA aptamer bound to exosite 1 and we reported the structure of an RNA aptamer bound to exosite 2 on thrombin. Based upon these structural studies we speculated that the two aptamers would not compete for binding to thrombin. We observe that simultaneously blocking both exosites with the aptamers leads to synergistic inhibition of thrombin-dependent platelet activation and procoagulant activity. This combination of exosite 1 and exosite 2 inhibitors may provide a particularly effective antithrombotic approach.

Isolation and characterization of a baculovirus associated with the insect parasitoid wasp, Cotesia marginiventris, or its host, Trichoplusia ni.

A multiple nucleopolyhedrovirus (MNPV) was isolated from Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae) larvae that had been stung by the parasitoid Cotesia marginiventris (Cresson) (Hymenoptera: Braconidae). The wild type virus was plaque purified by infecting a Heliothis subflexa (BCIRL- HsAM1) cell line and isolating several clones. The mean estimated genomic size of this virus based on PstI, BstEII, StyI, HindIII restriction profiles was estimated to be 106 +/- 2.5 kbp (mean+/-SE). A clone designated as TnMNPV/CmBCL9 was used in bioassays against several lepidopteran pests and in comparative studies with the baculoviruses AcMNPV, AgMNPV, AfMNPV, PxMNPV and HzSNPV of Autographa califomica, Anticarsia gemmatalis, Anagrapha falcifera, Plutella xylostella, and Helicoverpa zea, respectively. Infectivity studies showed that TnMNPV/CmBCL9 was highly infectious for Heliothis subflexa and T. ni, with an LC(50) value 0.07 occlusion bodies/mm(2) in both species and also infectious for H. zea and Heliothis virescens with LC(50) values of 0.22 and 0.27 occlusion bodies/mm(2), respectively. Restriction endonuclease analysis of the isolate and selected baculoviruses revealed profiles that were very similar to AfMNPV but different from the restriction endonuclease profiles of the other baculoviruses. Hybridization studies suggest that the TnMNPV/CmBCL9 was closely related to AfMNPV and AcMNPV-HPP. Further support for this comes from a phylogenetic analysis employing a split-graphs network, comparing the polh, egt, and p10 genes from TnMNPV/CmBCL9 with those from other baculoviruses and suggests that this virus is closely related to the AcMNPV variants, AfMNPV and RoMNPV of Rachiplusia ou.

MORE EFFICIENT PLANTS: A Consequence of Rising Atmospheric CO2?

The primary effect of the response of plants to rising atmospheric CO2 (Ca) is to increase resource use efficiency. Elevated Ca reduces stomatal conductance and transpiration and improves water use efficiency, and at the same time it stimulates higher rates of photosynthesis and increases light-use efficiency. Acclimation of photosynthesis during long-term exposure to elevated Ca reduces key enzymes of the photosynthetic carbon reduction cycle, and this increases nutrient use efficiency. Improved soil-water balance, increased carbon uptake in the shade, greater carbon to nitrogen ratio, and reduced nutrient quality for insect and animal grazers are all possibilities that have been observed in field studies of the effects of elevated Ca. These effects have major consequences for agriculture and native ecosystems in a world of rising atmospheric Ca and climate change.

Primary Production in Grasslands and Coniferous Forests with Climate Change: An Overview.

In energy terms primary production is the driving step of the global carbon cycle. To predict the interaction of ecosystems with the "greenhoude" effect, it is necessary to understand how primary production, consumption, and decomposition will respond to climate change. Most estimates of primary production have been made by extrapolation from measured standing crops. For grasslands we show this approach to be seriously in error. Even where detailed studies of turnover and belowground production have been undertaken, errors are invariably high, severely limiting the value of models based on correlation of climate with measured production. Detailed information is available on the responses of individual plant processes to individual climatic variables at the leaf, plant, and stand level, giving potential for a more mechanistic approach in modelling. This approach is limited by lack of information on multivariate interactions and on some key physiological processes, and by uncertainties in scaling up to populations and communities. Despite this, some important insights to possible community responses, particularly those of C3 and C4 types, may be gained from knowledge of responses at the plant level and below. This review outlines the expected character of climate change in grasslands and coniferous forests. Knowledge of the responses of different physiological processes underlying production to individual aspects of climate change is considered, and its implications for higher levels of organization are discussed. Although feasible, mechanistic models of production compound the errors associated with individual process responses with uncertainties surrounding interaction and scaling up, and result in very large errors in any prediction of response to climate change. We conclude that there is insufficient information to predict accurately the response of primary production to climate change. The key processes for which information is inadequate and the parameters that have meaning at different scales need to be identified. Of particular promise is the approach of predicting production from light interception and conversion efficiency.