Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We ...have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers.
Background. The current West Africa Ebola virus disease (EVD) outbreak has resulted in multiple individuals being medically evacuated to other countries for clinical management. Methods. We report ...two patients who were transported from West Africa to the United States for treatment of EVD. Both patients received aggressive supportive care measures, as well as an investigational therapeutic (TKM-100802) and convalescent plasma. Results. While one patient experienced critical illness with multi-organ failure requiring mechanical ventilation and renal replacement therapy, both patients recovered without serious long-term sequelae to date. Conclusions. It is unclear what role the experimental drug and convalescent plasma had in the recovery of these patients. Prospective clinical trials are needed to delineate the role of investigational therapies in the care of patients with EVD.
We developed allometric equations for small-diameter woody species growing on mixed forest marginal lands, which are potential sources of biomass for bioenergy. Eleven species of trees and shrubs ...were sampled from a site located in eastern Canada. Equations derived in this study generally performed better than equations from the literature. Also, fixed-area plots (FAP) and line-intersect sampling (LIS) methods using both random or systematic selection of sampling units were compared to determine which method required the lowest number of measurements to estimate stand biomass for the same precision.
The fixed-area plots method was successfully used to estimate relatively accurately oven-dry biomass per hectare. Results indicated that potentially harvestable woody biomass (oven dry basis) varied between 33-41 and 12–13 t ha−1 for the most and least productive marginal sites respectively. On the most productive site, LIS estimates (between 20 and 42 t ha−1) were usually lower than those obtained using different FAP sampling methods (i.e. systematic or random, small (50 m2) or large (100 m2) plots), but similar on the more open sites (between 10 and 14 t ha−1). Small FAP resulted in a plot without measurements in one case. Moreover, estimates based on small FAP were generally higher, even if not significantly different from larger plot estimates. We therefore suggest using FAP with 100 m2 plots to estimate small-diameter woody biomass on marginal lands with dense vegetation, while LIS, even if promising for open stands, needs further evaluation before recommendation.
•Development of new allometric equations for 11 small woody species on marginal lands.•Comparison of sampling methods and estimation of harvestable biomass at the stand level.•Fixed-area plots of 100 m2 are recommended for young stands located on marginal lands.•Further testing of line-intersect sampling and other methods is suggested.
Systems integration (SIS) simulation and system-focused debriefing is an approach to test new processes with health care teams to inform its design and utility and identify systems issues ...proactively. Learner-focused simulations support team training with a focus on individual knowledge and skills. These strategies combined provide a highly effective quality improvement approach to test and implement new processes. This article will describe how we used SIS followed by learner-focused simulations and debriefings to introduce, test, refine, and train our team on a new, locally adapted cardiac arrest protocol after cardiac surgery (early chest opening).
•We used an effective simulation-based quality improvement approach to test and implement a new protocol.•The use of simulation for systems integration and debriefing to implement new processes informs the design and utility and identifies systems issues proactively.•The adoption of this protocol resulted in paradigm shift in early postoperative management and significant practice changes.•The teamwork constructs evaluated by the MHPTS showed statistically significant higher scores after session.•This approach ensured a safe and reliable implementation of a high-risk, low-frequency protocol.
Short-rotation intensive culture (SRIC) for bioenergy production is at its pre-commercial stage in Canada. To be economically viable, these types of plantations need an accurate examination of actual ...yields, which requires precise and efficient estimation methods (i.e., specific allometric equations and sampling methods). At six SRIC plantations from three Canadian provinces (Quebec, Ontario and Alberta), 6 willow and 10 poplar clones were sampled and clone allometric equations were developed to estimate plant biomass. A stem selection approach was successfully used to develop plant allometric equations, reducing the number of stems to be measured by up to 81% in coppiced plantations relative to traditional stem equations. Clone-specific equations were more accurate than equations for groups of clones, but the difference in terms of RMSE% was generally small (less than 5%). Using extensive measurements of all the plants inside a plantation and a simulation approach, we also compared five sampling methods (simple random sampling, stratified sampling, systematic sampling, random and systematic cluster sampling) to estimate total biomass inside the plantation. Simple random sampling and stratified random sampling were the most efficient methods (i.e., increased precision for equal sample size) for the estimation of average plant biomass, survival and total plantation biomass. Stratified random sampling (based on the position inside the plantation) made it possible to reduce the sample size as compared to simple random sampling, but only at higher levels of precision (e.g., 25 less plants at 5% precision). Applications of sampling using remote sensing techniques and GIS are briefly discussed.
•We developed biomass equations and sampling methods for SRIC plantations.•Clone-specific equations are more accurate than equations for groups of clones.•… but the difference in terms of RMSE% is generally small (less than 5%).•Stem selection reduces the number of stems to be measured by up to 81%.•For total biomass, simple random sampling and stratified sampling are the most efficient.
Immunohistochemical analyses of archival tumor specimens were used for pre-planned exploratory analyses of protocol-specified candidate biomarkers of bortezomib activity in 73 patients with ...relapsed/refractory mantle cell lymphoma in the phase 2 PINNACLE study. Consistent with other studies, elevated Ki-67 was a marker of poor prognosis, demonstrating significant associations with shorter time to progression and overall survival. Elevated NF-κB p65 and low PSMA5 expression demonstrated a trend for better response and were significantly associated with longer time to progression; elevated NF-κB p65 demonstrated a trend toward longer overall survival. This is consistent with myeloma clinical genomics research, suggesting biomarker relevance across tumor types. Elevated p27 was significantly associated with longer overall survival. Overall survival analyses by International Prognostic Index and Mantle Cell Lymphoma International Prognostic Index confirmed differential prognosis by both scores. These biomarkers data begin to illuminate bortezomib's mechanism of action in lymphoma.
Background: Mantle cell lymphoma (MCL) is an aggressive NHL subtype that remains incurable in most cases with conventional chemotherapy. However, individual patient survival can vary considerably, ...and studies have identified potential markers of prognostic subgroups, including Ki-67 and the cyclin-dependent kinase (CDK) inhibitor p27. Genomic studies further highlight tumor proliferation status as the major driver of differential prognosis in MCL (Rosenwald et al, Cancer Cell 2003). Such studies were conducted prior to the introduction of bortezomib, a first-in-class proteasome inhibitor that was recently approved for the treatment of relapsed MCL. Plausible hypotheses for the activity of this novel agent in MCL include inhibition of NF-κB activity and disruption of the cell cycle via stabilization of CDK inhibitors such as p27. In order to test these hypotheses directly and also examine how this new agent impacts prognostic subgroups of MCL, the PINNACLE trial, the largest phase 2 study of bortezomib in MCL, specified the collection of archived tumor specimens for immunohistochemical (IHC) analyses. In this trial 155 relapsed/refractory MCL patients received single-agent bortezomib at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles. A 33% overall response rate was observed (8% CR/CRu), with a median time to progression (TTP) of 6.2 months and a responder TTP of 10.6 months (Fisher et al, J Clin Oncol 2006).
Methods: A series of unstained tumor slides from the diagnostic tumor specimens were collected from a subset of 70 evaluable patients. This subset formed the basis of the current IHC analysis and the clinical parameters of this subset appeared similar to those of the study as a whole. Several proteins were assessed via IHC; these included p27, SKP2, cyclin D1, and Ki-67, as well as candidate markers correlated with bortezomib efficacy in a genomic study of multiple myeloma, including NF-κB and proteasome subunits (Mulligan et al, Blood 2007). Association with response was evaluated using Fisher's Exact Test. A Cox proportional hazard linear model adjusted for clinical covariates was used to determine the effect of these parameters on TTP.
Results: In this subset analysis no protein markers were significantly associated with response to therapy. However, patients with >50% Ki-67-positive tumor cells were more likely to progress than patients with <50% Ki-67-positive tumor cells (p<0.05). Those with higher tumor α-5 proteasome subunit expression score (≥3+) exhibited shorter TTP relative to those with <3+ (p<0.05). High levels of NF-κB p65 (≥2+) were associated with longer TTP than levels <2+ (p<0.05). Analyses of updated patient survival are ongoing.
Conclusions: These studies indicate that tumor proliferative rate, as assessed by Ki-67 staining, retains prognostic significance for TTP in bortezomib-treated patients. The prognostic significance of p65 and the α-5 proteasome subunit suggests these pathways may be relevant to outcomes after bortezomib treatment and should be further evaluated for prognostic and/or predictive utility.
L’objectif des travaux présentés dans cette thèse est d’étudier la diffusion de l’information dans les marchés financiers. Considérant comme établi que les individus sont hétérogènes et à ...rationalité limitée, nous avons fondé nos travaux sur une catégorie de modèles computationnels dans le but de simuler les actions et les interactions des agents autonomes. Cette catégorie est communément nommée modélisation agent (ABM).Plus concrètement, cette recherche se concentre sur le rôle de l’hétérogénéité des agents dans la diffusion et l’utilisation de l’information. À cet effet, nous avons développé deux structures de marché, qui diffèrent par leur transparence. Dans les chapitres 1 et 2, nous introduisons un marché centralisé, où une partie du carnet d’ordre est accessible (information publique). Dans le chapitre 3, nous développons un marché de gré à gré dans lequel les agents négocient et échangent avec leurs relations.
The piece of work’s aim is to understand information diffusion in financial markets. Starting from the empirical evidences that agents are heterogeneous and bounded rational, we based our investigations on a class of computational models for simulating the actions and interactions of autonomous agents: the agent - based model (ABM). More precisely, this research focuses on the impacts of agents heterogeneity in diffusion and use of information. For this purpose, we developed two market structures, in which the market transparency varies. In the chapters 1 and 2, we introduce a centralised market, where a part of the order-book is available as a public information. In the chapter 3, we build an Over-The-Counter market, where agents bargains with their trading contacts.
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