Climatology and atmospheric chemistry of the non-methane hydrocarbons ethane and propane over the North Atlantic

A record spanning ten years of non-methane hydrocarbon (NMHC) data from the Pico Mountain Observatory (PMO), Pico Island, Azores, Portugal, was analyzed for seasonal NMHC behavior, atmospheric processing, and trends, focusing on ethane and propane. The location of this site in the central North Atlantic, at an elevation of 2225 m asl, allows these data to be used to investigate the background conditions and pollution transport events occurring in the lower free North Atlantic troposphere. The quantity ln([propane]/[ethane]) was used as an indicator of both photochemical processing and a marker for the occurrence of pollution transport events detected at the station. The Pico data were compared with three other continuous NMHC data sets from sites bordering the North Atlantic, i.e. the Global Atmospheric Watch (GAW) stations at Summit, Greenland, Hohenpeisssenberg, Germany, and Cape Verde, using ln([propane]/[ethane]) results as an indicator for the degree of photochemical processing (aging) seen in the data. Comparisons of these three data sets showed some significant differences in the seasonal background and range of observed values. The statistical distribution of binned monthly data was determined, and individual sample events were then scaled to the monthly median observed value. Back trajectories, determined by the HYSPLIT model were used to investigate the geographic origin of the observed trace gases as a function of the degree of photochemical processing. Results show that PMO samples have been subjected to a diversity of air transport and aging, from highly processed air to freshly emitted air throughout the year, and in particular during summer months. The predominant air transport is from North America, with only occasional influence from continental areas located east and southeast (Europe and Africa). The available record was found to be too variable and still too short to allow deciphering NMHC trends from the data. Ethane and propane measurements at the PMO were compared with the MOZART-4 atmospheric chemistry and transport model at the appropriate time and location. The model was found to yield good agreement in the description of the lower range of atmospheric mole fractions observed, of the seasonal cycle, and the regional oxidation chemistry. However, ethane and propane enhancements in transport events were underestimated, indicating that after the 3 days of synoptic transport to PMO the spatial extent of plumes frequently is smaller than the 2.8x2.8 (300 km) model grid resolution

Test 1157: John Deere 2630 and 2640 Diesel

EXPLANATION OF TEST REPORT GENERAL CONDITIONS East tractor is a production model equipped for common usage. Power consuming accessories can be disconnected only when it is convenient for the operator to do so in practice. Additional weight can be added as ballast if the manufacturer regularly supplies it for sale. The static tire loads and the inflation pressures muse conform to recommendations in the Tire Standards published by the Society of Automotive Engineers. PREPARATION FOR PERFORMANCE RUNS The engine crank case is drained and refilled with a measured amount of new oil conforming to specifications in the operator’s manual. The fuel used and the maintenance operations must also conform to the published information delivered with the tractor. The tractor is then limbered-up for 1 hour on drawbar work in accordance with the manufacturers published recommendations. The manufacturer’s representative is present to make appropriate decisions regarding mechanical adjustments. The tractor is equipped with approximately the amount of added ballast that is used during maximum drawbar tests. The tire tread-bar height must be at least 65% of new tread height prior to the maximum power run. BELT OR POWER TAKE-OFF PERFORMANCE Maximum Power and Fuel Consumption. The manufacturer’s representative makes carburetor, fuel pump, ignition and governor control settings which remain unchanged throughout tall subsequent runs. The governor and the manually operated governor control lever is set to provide the high-idle speed specified by the manufacturer for maximum power. Maximum power is measured by connecting the belt pulley or the power take-off to a dynamometer. The dynamometer load is then gradually increased until the engine is operating at the rated speed specified by the manufacturer for maximum power. The corresponding fuel consumption is measured. Varying Power and Fuel Consumption. Six different horsepower levels are used to show corresponding fuel consumption rates and how the governor causes the engine to react to the following changes in dynamometer load: 85% of the dynamometer torque at maximum power; minimum dynamometer torque, ½ the 85% torque; maximum power; ¼ and ¾ of the 85% torque. Since at tractor is generally subjected to varying loads the average of the results in this test serve well for predicting the fuel consumption of a tractor in general usage. DRAWBAR PERFORMANCE All engine adjustments are the same as those used in the belt or power take-off tests. If the manufacturer specifies a different rated crankshaft speed for drawbar operations, then the position of the manually operated governor control is changed to provide the high-idle speed specified by the manufacturer in the operating instructions. Varying Power and Fuel Consumption With Ballast. The varying power runs are made to show the effect of speed-control devices (engine governor, automatic transmissions, etc.) on horsepower, speed and fuel consumption. These runs are made around the entire test course with has two 180 degree turns with a minimum radius of 50 feet. The drawbar pull is set at 3 different levels as follows: (1) as near to the pull a maximum power as possible and still have the tractor maintain the travel speed at maximum horsepower on the straight sections of the test course; (2) 75% of the pull at maximum power; and (3) 50% of the pull at maximum power. Prior to 1958, fuel consumption data (10 hour test) were shown only for the pull obtained at maximum power for tractors having torque converters and at 75% of the pull obtained at maximum power for gear-type tractors. Maximum Power With Ballast. Maximum power is measured on straight level sections of the test course. Data are shown for not more that 12 different gears or travel speeds. Some gears or travel speeds may be omitted because of high slippage of the traction members or because the travel speed may exceed the safe-limit for the test course. The maximum safe speed for the Nebraska Test course has been set at 15 miles per hour. The slippage limits have been set at 15% and 7% for pneumatic tires and steel tracks or lugs, respectively. Higher slippage gives widely varying results. Maximum Power Without Ballast. All added ballast is removed from the tractor. The maximum drawbar power of the tractor is determined by the same procedure used for getting maximum power with ballast. The gear (or travel speed) is the same as that used in the 10-hours test. Varying Power and Travel Speed With Ballast. Travel speeds corresponding to drawbar pulls beyond the maximum power range are obtained to show the “lugging ability” of the tractor. The run starts with the pull at maximum power; then additional drawbar pull is applied to cause decreasing speeds. The run is ended by one of three conditions; (1) maximum pull is obtained, (2) the maximum slippage limit is reached, or (3) some other operating limit is reached

A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on “blastomas,” which variably recapitulate the morphologic maturation of organs from which they originate

Optimising biomarkers for accurate ependymoma diagnosis, prognostication and stratification within International Clinical Trials: A BIOMECA study

BACKGROUND: Accurate identification of brain tumour molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study. METHODS: Across six European BIOMECA laboratories we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via FISH and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH. RESULTS: DNA Methylation profiling classified 65.3% (n=96/147) of cases as EPN-PFA and 15% (n=22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99-100% across three centres). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP1- fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-centre concordance and low sensitivity and specificity whilst MIP, MLPA and DNA methylation-based approaches demonstrated greater accuracy. CONCLUSIONS: We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q and CDKN2A loss whilst FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches

Molecular, pathological, radiological, and immune profiling of non-brainstem pediatric high-grade glioma from the HERBY phase II randomized trial

The HERBY trial was a phase II open-label, randomized, multicenter trial evaluating bevacizumab (BEV) in addition to temozolomide/radiotherapy in patients with newly diagnosed non-brainstem high-grade glioma (HGG) between the ages of 3 and 18 years. We carried out comprehensive molecular analysis integrated with pathology, radiology, and immune profiling. In post-hoc subgroup analysis, hypermutator tumors (mismatch repair deficiency and somatic POLE/POLD1 mutations) and those biologically resembling pleomorphic xanthoastrocytoma ([PXA]-like, driven by BRAF_V600E or NF1 mutation) had significantly more CD8+ tumor-infiltrating lymphocytes, and longer survival with the addition of BEV. Histone H3 subgroups (hemispheric G34R/V and midline K27M) had a worse outcome and were immune cold. Future clinical trials will need to take into account the diversity represented by the term ‘‘HGG’’ in the pediatric population

A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era.

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on blastomas, which variably recapitulate the morphologic maturation of organs from which they originate. SIGNIFICANCE: In this review, we briefly summarize the main features and updates of each chapter of the inaugural WHO Classification of Pediatric Tumors, including its rapid transition from a mostly microscopic into a molecularly driven classification systematically taking recent discoveries in pediatric tumor genomics into account

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Radiomic signatures of posterior fossa ependymoma: Molecular subgroups and risk profiles

BACKGROUND: The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB. METHODS: We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers. RESULTS: For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (p < 0.0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (p = 0.002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86. CONCLUSIONS: We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy

Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse

BACKGROUND: 90% of tumors) and established genetic drivers (e.g. SHH/WNT/P53 mutations; 60% of rMB events) were maintained from diagnosis. Critically, acquired and maintained rMB events converged on targetable pathways which were significantly enriched at relapse (e.g. DNA damage-signaling) and specific events (e.g. 3p loss) predicted survival post-relapse. CONCLUSIONS: rMB is defined by the emergence of novel events and pathways, in concert with selective maintenance of established genetic drivers. Together, these define the actionable genetic landscape of rMB and provide a basis for improved clinical management and development of stratified therapeutics, across disease-course