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Molecular characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases remains unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 cases (81% of the cohort). The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)) or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3AK27M (2%) or IDH1R132H (0.5%) mutations, as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of KIAA1549-BRAF fused patients compared to BRAFV600E with 10-year OS 97.7% (95%, CI 95.5-100) and 83.9% (95%, CI 72.5-95.6), respectively. In addition to survival, molecular alterations predicted differences in response to conventional therapeutics; BRAF fused patients showed a 46% response-rate, versus only 14% in V600E patients. pLGGs harboring H3F3AK27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.
Introduction: Patients with Heart failure (HF) experience frequent decompensation necessitating multiple emergency department (ED) visits and hospitalizations. If patients are able to receive timely interventions and optimize self-management, recurrent ED visits may be reduced. In this feasibility study, we piloted the application of home telemonitoring to support the discharge of HF patients from hospital to home. We hypothesized that TEC4Home would decrease ED revisits and hospital admissions and improve patient health outcomes. Methods: Upon discharge from the ED or hospital, patients with HF received a blood pressure cuff, weight scale, pulse oximeter, and a touchscreen tablet. Participants submitted measurements and answered questions on the tablet about their HF symptoms daily for 60 days. Data were reviewed by a monitoring nurse. From November 2016 to July 2017, 69 participants were recruited from Vancouver General Hospital (VGH), St. Pauls Hospital (SPH) and Kelowna General Hospital (KGH). Participants completed pre-surveys at enrollement and post-surveys 30 days after monitoring finished. Administrative data related to ED visits and hospital admissions were reviewed. Interviews were conducted with the monitoring nurses to assess the impact of monitoring on patient health outcomes. Results: A preliminary analysis was conducted on a subsample of participants (n=22) enrolled across all 3 sites by March 31, 2017. At VGH and SPH (n=14), 25% fewer patients required an ED visit in the post-survey reporting compared to pre-survey. During the monitoring period, the monitoring nurse observed seven likely avoided ED admissions due to early intervention. In total, admissions were reduced by 20% and total hospital length of stay reduced by 69%. At KGH (n=8), 43% fewer patients required an ED visit in the post-survey reporting compared to the pre-survey. Hospital admissions were reduced by 20% and total hospital length of stay reduced by 50%. Overall, TEC4Home participants from all sites showed a significant improvement in health-related quality of life and in self-care behaviour pre- to 90 days post-monitoring. A full analysis of the 69 patients will be complete in February 2018. Conclusion: Preliminary findings indicate that home telemonitoring for HF patients can decrease ED revisits and improve patient experience. The length of stay data may also suggest the potential for early discharge of ED patients with home telemonitoring to avoid or reduce hospitalization. A stepped-wedge randomized controlled trial of TEC4Home in 22 BC communities will be conducted in 2018 to generate evidence and scale up the service in urban, regional and rural communities. This work is submitted on behalf of the TEC4Home Healthcare Innovation Community.
Fish-hooks discovered among grave goods associated with an adult female burial at the Tron Bon Lei rockshelter on the island of Alor in Indonesia are the first of their kind from a Pleistocene mortuary context in Southeast Asia. Many of the hooks are of a circular rotating design. Parallels found in various other prehistoric contexts around the globe indicate widespread cultural convergence. The association of the fish-hooks with a human burial, combined with the lack of alternative protein sources on the island, suggest that fishing was an important part of the cosmology of this community. The Tron Bon Lei burial represents the earliest-known example of a culture for whom fishing was clearly an important activity among both the living and the dead.
We present mid-IR and far-IR images of a variety of AGB stars and red supergiants. The mid-IR images were all taken with the Berkeley/Livermore mid-IR array camera, which employs a 10 × 64 pixel Hughes photoconductor. All the images reported here were taken using a 10% bandpass CVF, at various wavelengths in the 10μm atmospheric window. These were supplemented by IRAS images, some constructed from survey scans, others made as Additional Observations during the pointed phase of the IRAS mission. We have so far observed 11 such sources with our mid-IR camera, and report here that only two of them (R Aql and V Hya) appear to be unresolved.
Gender equity is imperative to the attainment of healthy lives and wellbeing of all, and promoting gender equity in leadership in the health sector is an important part of this endeavour. This empirical research examines gender and leadership in the health sector, pooling learning from three complementary data sources: literature review, quantitative analysis of gender and leadership positions in global health organisations and qualitative life histories with health workers in Cambodia, Kenya and Zimbabwe. The findings highlight gender biases in leadership in global health, with women underrepresented. Gender roles, relations, norms and expectations shape progression and leadership at multiple levels. Increasing women's leadership within global health is an opportunity to further health system resilience and system responsiveness. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equity.
We present very high signal-to-noise observations of the (1,0) and (0,0) vibrational bands of interstellar CN near 3580 and 3874 Å toward HD 21483. Corrected for saturation with a derived b-value of 1.29±0.05 km s-1, these CN line strengths yield excitation temperatures of 2.83±0.09 and 2.76±0.07 K for the J=1-2 and J=0-1 rotational transitions at 1.32 and 2.64 mm. In the absence of local CN excitation, these values represent the brightness temperature of the cosmic microwave background (CMB) radiation at these wavelengths. Millimeter observations have revealed no CN emission at 2.64 mm toward HD 21483 and allow us to set a 2σ upper limit of 0.11 K on the contribution of local processes to the J=0-1 excitation. Considering this limit and the lesser likelihood of local J=1-2 excitation, our observations indicate a CMB temperature of 2.83±0.09 K at 1.32 mm.
Government transparency is widely promoted, yet little is known about transparency’s effects. Survey experiments reported here, made on the streets of Lima, Peru, investigate a simple question: what are the effects of government-sponsored transparency websites, and the information revealed by those efforts, on attitudes about the Peruvian political system? Like many developing countries, Peru lacks much system support, making it more difficult to improve governance and democracy; transparency itself has little impact on political attitudes. However, some dimensions of the information provided by transparency matter: endorsement by a credible third party or framing that associates comparatively good community well-being with government performance. These conditions substantively increase Peruvians’ approval of the national political community, the regime’s performance, institutions, and local government.
Carbon films were energetically deposited onto copper foil using the physical vapor deposition technique filtered cathodic vacuum arc. Raman spectroscopy and x-ray absorption spectroscopy showed that high quality graphene films of uniform thickness can be deposited onto copper foil at temperatures of 850 °C. The films can be prepared at high deposition rates (∼1 nm/min) and were comparable to graphene films grown at 1050 °C using chemical vapor deposition. This lower growth temperature was made possible by the energetic carbon flux which assisted the arrangement of carbon atoms into graphene layers on the Cu growth surface. Floating substrate potential was found to produce the highest quality graphene and the addition of hydrogen gas during film growth resulted in more defective films.
A cloud screening method initially generated to mask cloud contaminated pixels over the ocean in visible/infrared imagery, has been revised and adapted to detect clouds over Arctic regions with encouraging results. Although the method is quite successful in eliminating very cold clouds, it underestimates low level clouds. However, this does not appear to interfere with monitoring of ice related features such as leads or the ice edge in Advanced Very High Resolution Radiometer (AVHRR) scenes. The method uses: a multiple-band approach to produce signatures not readily available in single channel data, an edge detection/dilation technique to locate features in the clouds and to join isolated edges, and a polygon identification technique to remove noise in the form of isolated pixels and separate clear regions from cloud contaminated areas. The method has been tested over a limited set of data with consistent results. Initial evaluation of the usefulness of this cloud-detection algorithm in data-fusion experiments indicate a potential in locating areas in AVHRR data which are cloud contaminated and which could yield a far superior representation of the ice features if replaced with data from a different sensor such as the Special Sensor Microwave/lmager (SSM/I).
A point mutation resulting in a specific amino acid change(K27M) in either one of the genes encoding histone H3, H3F3A (H3.3) or HIST1H3B/C/I (H3.1)is present in most pediatric intrinsic pontine gliomas, and has been described in other midline locations. The objective of the present study was to determine the frequency and location of this mutation in diffuse infiltrating gliomas in young adults. The study group consisted of 22 consecutive diffuse gliomas in patients under the age of 40 treated at St. Michael’s Hospital, an adult hospital in the University of Toronto system. Ultra-sensitive digital droplet PCR, a method capable of highly sensitive and specific mutation detection affecting either H3.3 or H3.1, was performed on sample DNA to determine H3K27M status. The H3K27M mutation was detected in the gliomas of five patients, aged 17 to 34 years. The male: female ratio was 3:2. The allele frequency ranged from 26% to 44%, reflecting the infiltrating character of the tumors. Three of the tumors where located in the thalamus, one in the medulla, and one was intraventricular. In terms of grading, one tumor was considered WHO grade II, two III, and two IV. In contrast, most tumors in patients with gliomas lacking the K27M mutation (17 subjects, age 19 to 39 years) were located in the lobes of the cerebral hemispheres, with the following exceptions: 1 in the thalamus, 1 in the hypothalamus, 1 in the cerebellum, and 1 periventricular. WHO grades were 1 II, 9 III, 7 IV. Correlation with patient outcome is ongoing. We conclude that the H3K27M is common in thalamic gliomas in young adult patients, and rare or absent in lobar hemispheric gliomas.
An upper limit on the space density of quasars at z > 5 is obtained independent of any optical magnitude limit, from the complete identification of a large sample of flat-spectrum radio sources. This upper limit is below the observed space density at z ≃ 2 − 3, showing that the turnover in space density is real and not merely due to obscuration.
The Center for Astrophysical Research in Antarctica conducts various educational outreach programs as part of its mission as a National Science Foundation Science and Technology Center. The method behind the outreach programs is one of forging partnerships between Center researchers and other educational organisations. The main program serves primary and secondary students in Chicago. The core of the program is called Space Explorers and is targeted at high school students. These students attend a summer residential institute at the University of Chicago’s Yerkes Observatory. The high school Space Explorers then extend the reach of the program during the academic year by teaching in primary schools using a portable planetarium. The Center also pursues many other outreach activities and is in the process of forming an Antarctic Education Alliance.
Realization that hard coastal infrastructures support lower biodiversity than natural habitats has prompted a wealth of research seeking to identify design enhancements offering ecological benefits. Some studies showed that artificial structures could be modified to increase levels of diversity. Most studies, however, only considered the short-term ecological effects of such modifications, even though reliance on results from short-term studies may lead to serious misjudgements in conservation. In this study, a seven-year experiment examined how the addition of small pits to otherwise featureless seawalls may enhance the stocks of a highly-exploited limpet. Modified areas of the seawall supported enhanced stocks of limpets seven years after the addition of pits. Modified areas of the seawall also supported a community that differed in the abundance of littorinids, barnacles and macroalgae compared to the controls. Responses to different treatments (numbers and size of pits) were species-specific and, while some species responded directly to differences among treatments, others might have responded indirectly via changes in the distribution of competing species. This type of habitat enhancement can have positive long-lasting effects on the ecology of urban seascapes. Understanding of species interactions could be used to develop a rule-based approach to enhance biodiversity.