Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Wetlands are the world's largest natural source of methane, a powerful greenhouse gas. The strong sensitivity of methane emissions to environmental factors such as soil temperature and moisture has led to concerns about potential positive feedbacks to climate change. This risk is particularly relevant at high latitudes, which have experienced pronounced warming and where thawing permafrost could potentially liberate large amounts of labile carbon over the next 100 years. However, global models disagree as to the magnitude and spatial distribution of emissions, due to uncertainties in wetland area and emissions per unit area and a scarcity of in situ observations. Recent intensive field campaigns across the West Siberian Lowland (WSL) make this an ideal region over which to assess the performance of large-scale process-based wetland models in a high-latitude environment. Here we present the results of a follow-up to the Wetland and Wetland CH₄ Intercomparison of Models Project (WETCHIMP), focused on the West Siberian Lowland (WETCHIMP-WSL). We assessed 21 models and 5 inversions over this domain in terms of total CH₄ emissions, simulated wetland areas, and CH₄ fluxes per unit wetland area and compared these results to an intensive in situ CH₄ flux data set, several wetland maps, and two satellite surface water products. We found that (a) despite the large scatter of individual estimates, 12-year mean estimates of annual total emissions over the WSL from forward models (5.34 ± 0.54 Tg CH₄ yr^-1), inversions (6.06 ± 1.22 Tg CH₄ yr^-1), and in situ observations (3.91 ± 1.29 Tg CH₄ yr^-1) largely agreed; (b) forward models using surface water products alone to estimate wetland areas suffered from severe biases in CH₄ emissions; (c) the interannual time series of models that lacked either soil thermal physics appropriate to the high latitudes or realistic emissions from unsaturated peatlands tended to be dominated by a single environmental driver (inundation or air temperature), unlike those of inversions and more sophisticated forward models; (d) differences in biogeochemical schemes across models had relatively smaller influence over performance; and (e) multiyear or multidecade observational records are crucial for evaluating models' responses to long-term climate change.

Climate factors including soil temperature and moisture, incident solar radiation, and atmospheric carbon dioxide concentration are important environmental controls on methane (CH₄) emissions from northern wetlands. We investigated the spatiotemporal distributions of the influence of these factors on northern high-latitude wetland CH₄ emissions using an enhanced version of the Variable Infiltration Capacity (VIC) land surface model. We simulated CH₄ emissions from wetlands across the pan-Arctic domain over the period 1948–2006, yielding annual average emissions of 36.1 ± 6.7 Tg CH₄ yr^-1 for the period 1997–2006. We characterized historical sensitivities of CH₄ emissions to air temperature, precipitation, incident long- and shortwave radiation, and atmospheric [CO₂] as a function of average summer air temperature and precipitation. Emissions from relatively warm and dry wetlands in the southern (permafrost-free) portion of the domain were positively correlated with precipitation and negatively correlated with air temperature, while emissions from wetter and colder wetlands further north (permafrost) were positively correlated with air temperature. Over the entire period 1948–2006, our reconstructed CH₄ emissions increased by 20 %, the majority of which can be attributed to an increasing trend in summer air temperature. We estimated future emissions in response to 21st century warming as predicted by CMIP5 (Coupled Model Intercomparison Project Phase 5) model projections to result in end-of-century CH₄ emissions 38–53 % higher than our reconstructed 1997–2006 emissions, accompanied by the northward migration of warmer and drier than optimal conditions for CH₄ emissions, implying a reduced role for temperature in driving future increases in emissions.

Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.

Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.

Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.