The diagnosis of central nervous system tumours has been transformed in recent years from a microscopic morphology-based process to one dominated by the identification of somatic genetic alterations in tumour cells. This switch requires implementing radically different methods, for which appropriate training and financial resources must be allocated. The Canadian Association of Neuropathologists (CANP) has followed a process based on the scientific literature and consensus to develop recommendations for molecular testing of tumours of the brain and spinal cord, aiming to balance the need for treatment-determinant accurate diagnosis and the current limitations inherent in the transition to a new paradigm. The Professional Affairs Committee was charged with this task. A draft was discussed during the CANP general assembly, along with presentations from groups who had implemented molecular technologies, as well as others who relied on external laboratories. The Professional Affairs Committee summarised the consensus and submitted their recommendation to the CANP’s Executive Committee. A final report was posted on the CANP website for a month to allow all members to comment. The recommendations below apply to intrinsic tumours of the central nervous system and do not include metastatic disease or tumours impinging upon the nervous system from outside. These recommendations should be considered clinically relevant, as the results have direct consequences on the patient’s treatment, either through the use of targeted therapies or the trial-proven best application of radiation and/or chemotherapy.

Supraglacial debris cover regulates the melt rates of many glaciers in mountainous regions around the world, thereby modifying the availability and quality of downstream water resources. However, the influence of supraglacial debris is often poorly represented within glaciological models, due to the absence of a technique to provide high-precision, spatially continuous measurements of debris thickness. Here, we use high-resolution UAV-derived thermal imagery, in conjunction with local meteorological data, visible UAV imagery and vertically profiled debris temperature time series, to model the spatially distributed debris thickness across a portion of Llaca Glacier in the Cordillera Blanca of Peru. Based on our results, we simulate daily sub-debris melt rates over a 3-month period during 2019. We demonstrate that, by effectively calibrating the radiometric thermal imagery and accounting for temporal and spatial variations in meteorological variables during UAV surveys, thermal UAV data can be used to more precisely represent the highly heterogeneous patterns of debris thickness and sub-debris melt on debris-covered glaciers. Additionally, our results indicate a mean sub-debris melt rate nearly three times greater than the mean melt rate simulated from satellite-derived debris thicknesses, emphasising the importance of acquiring further high-precision debris thickness data for the purposes of investigating glacier-scale melt processes, calibrating regional melt models and improving the accuracy of runoff predictions.

Double-cropping winter rye cover crops (CC) with soybean in the North Central US could help with the global effort to sustainably intensify agriculture. Studies addressing the management of these systems are limited. Therefore, a field study was conducted from 2017 to 2019 in Central Iowa, US to evaluate winter rye CC biomass production, aboveground N accumulation, estimated economics, estimated within-field energy balance and estimated greenhouse gas (GHG) emissions under three N application rates (0, 60, 120 kg N ha−1) and three planting methods (pre- and post-harvest broadcast and post-harvest drilling). Averaged over N rates, all planting methods resulted in >5.0 Mg ha−1 year−1 rye aboveground biomass dry matter. Averaged over the 2-year study and compared with unfertilized treatments, applying 60 kg N ha−1 produced 1.1 Mg ha−1 more aboveground biomass (6.1 vs 5.0 Mg ha−1), accumulated 30 kg ha−1 more N in aboveground biomass (88 vs 58 kg N ha−1), and led to 20 GJ ha−1 more net energy. Biomass production was not significantly higher with 120 kg N ha−1 compared with the 60 kg N ha−1 rate. Even when accounting for an estimated 0.75 Mg ha−1 of above ground rye biomass left in the field after harvesting, more N was removed than applied at the 60 kg N ha−1 rate. The minimum rye prices over the 2-year study needed for double-cropping winter rye CC to be profitable (breakeven prices) averaged $117 and $104 Mg−1 for the 0 and 60 kg N ha−1 rates, which factors in estimated soybean yield reductions in 2019 compared with local averages but not off-site transportation. GHG emissions were estimated to increase approximately threefold between the unfertilized and 60 kg N ha−1 rates without considering bioenergy offsets. While environmental tradeoffs need further study, results suggest harvesting fertilized rye CC biomass before planting soybean is a promising practice for the North Central US to maximize total crop and net energy production.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

Wavelength-dispersive X-ray (WDX) spectroscopy was used to measure silicon atom concentrations in the range 35–100 ppm [corresponding to (3–9) × 1018 cm−3] in doped AlxGa1–xN films using an electron probe microanalyser also equipped with a cathodoluminescence (CL) spectrometer. Doping with Si is the usual way to produce the n-type conducting layers that are critical in GaN- and AlxGa1–xN-based devices such as LEDs and laser diodes. Previously, we have shown excellent agreement for Mg dopant concentrations in p-GaN measured by WDX with values from the more widely used technique of secondary ion mass spectrometry (SIMS). However, a discrepancy between these methods has been reported when quantifying the n-type dopant, silicon. We identify the cause of discrepancy as inherent sample contamination and propose a way to correct this using a calibration relation. This new approach, using a method combining data derived from SIMS measurements on both GaN and AlxGa1–xN samples, provides the means to measure the Si content in these samples with account taken of variations in the ZAF corrections. This method presents a cost-effective and time-saving way to measure the Si doping and can also benefit from simultaneously measuring other signals, such as CL and electron channeling contrast imaging.

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.

In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.

We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band ( ${\sim}60\%$ ), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.