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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.
Introduction: Hypertensive disorders of pregnancy (HDP), including preeclampsia, can develop or worsen in the early postpartum period, often following discharge from hospital, resulting in severe preventable maternal morbidity and mortality. Due to a lack of routine early out-patient follow-up, many women with postpartum HDP present to the emergency department (ED) with severe hypertension or symptoms of preeclampsia (e.g., headache). In the ED, postpartum HDP can be difficult for clinicians to recognize (due to vague presenting symptom) and manage (due to lower blood pressure targets and concern of medication safety). ED clinicians recognized a need for timely recognition and effective treatments for postpartum HDP in the ED to improve maternal outcomes. As such, as part of a multi-step quality improvement initiative, an interdisciplinary team developed and implemented a postpartum HDP management protocol (consisting of nursing and physician protocols and an electronic order set embedded in the electronic medical record). The aims of this specific project were to assess: 1) the use of this clinical management protocol in the ED; and 2) its impacts on clinical care. Methods: This quality improvement project used electronic medical records to identify: 1) ED visits for postpartum HDP for postpartum women ages 20-50; 2) utilization of the postpartum HDP order set; and 3) clinical care outcomes (consultation and admission). Patient population characteristics and clinical care measures were summarized with descriptive statistics and compared using a before and after design. Changes in the utilization of the protocol were assessed using run charts. Results: 540 women with postpartum HDP were seen in the four Calgary EDs in the 16-month period following protocol implementation compared with 335 women in the preceding 12 months. The protocol was used in 46% of these 540 women, and increased over the 16 month follow-up period. We found an increase in the frequency of consultation of specialists (47% to 52%) and admissions (26% to 29%) amongst these women after protocol implementation. Conclusion: This initial assessment demonstrated good uptake of a postpartum HDP management protocol including referral for consultation and admission to hospital for blood pressure management. Future steps include evaluation of the impacts of this management protocol on important patient outcomes.
Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of ~17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21.
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.
The third symposium on Remote Sensing of Snow and Ice, organized by the International Glaciological Society, took place in Boulder, Colorado, 17–22 May 1992. As part of this meeting a total of 21 papers was presented on snow and ice applications of Advanced Very High Resolution Radiometer (AVHRR) satellite data in polar regions. Also during this meeting a NASA sponsored Workshop was held to review the status of polar surface measurements from AVHRR. In the following we have summarized the ideas and recommendations from the workshop, and the conclusions of relevant papers given during the regular symposium sessions. The seven topics discussed include cloud masking, ice surface temperature, narrow-band albedo, ice concentration, lead statistics, sea-ice motion and ice-sheet studies with specifics on applications, algorithms and accuracy, following recommendations for future improvements. In general, we can affirm the strong potential of AVHRR for studying sea ice and snow covered surfaces, and we highly recommend this satellite data set for long-term monitoring of polar process studies. However, progress is needed to reduce the uncertainty of the retrieved parameters for all of the above mentioned topics to make this data set useful for direct climate applications such as heat balance studies and others. Further, the acquisition and processing of polar AVHRR data must become better coordinated between receiving stations, data centers and funding agencies to guarantee a long-term commitment to the collection and distribution of high quality data.
Seeds of the winter annual Bromus tectorum lose primary dormancy in summer and are poised to germinate rapidly in the autumn. If rainfall is inadequate, seeds remain ungerminated and may enter secondary dormancy under winter conditions. We quantified conditions under which seeds enter secondary dormancy in the laboratory and field and also examined whether contrasting B. tectorum genotypes responded differently to dormancy induction cues. The study also extends previous hydrothermal time models for primary dormancy loss and germination timing in B. tectorum by using similar models to account for induction and loss of secondary dormancy. Maximum secondary dormancy was achieved in the laboratory after 4 weeks at –1.0 MPa and 5°C. Seeds in the field became increasingly dormant through exposure to temperatures and water potentials in this range, confirming laboratory results. They were released from dormancy through secondary after-ripening the following summer. Different genotypes showed contrasting responses to dormancy induction cues in both laboratory and field. To examine secondary dormancy induction and release in the field in terms of hydrothermal time parameters, we first created a model that allowed mean base water potential (Ψb(50)) to vary while holding other hydrothermal time parameters constant, as in models for primary dormancy loss under dry conditions. The second model allowed all three model parameters to vary through time, to account for changes (e.g. hydrothermal time accumulation) that could occur simultaneously with dormancy induction in imbibed seeds. Shifts in Ψb(50) could explain most changes in dormancy status for seeds retrieved from the field, except during the short period prior to dormancy induction, when hydrothermal time was accumulating. This study illustrates that hydrothermal modelling, and specifically changes in Ψb(50), can be used to characterize secondary dormancy induction and loss in B. tectorum.
Little is known about cause-specific long-term mortality beyond 30 days in pneumonia. We aimed to compare the mortality of patients with hospitalized pneumonia compared to age- and sex-matched controls beyond 30 days. Participants were drawn from the European Prospective Investigation into Cancer (EPIC)-Norfolk prospective population study. Hospitalized pneumonia cases were identified from record linkage (ICD-10: J12-J18). For this study we excluded people with hospitalized pneumonia who died within 30 days. Each case identified was matched to four controls and followed up until the end June 2012 (total 15 074 person-years, mean 6·1 years, range 0·08–15·2 years). Cox regression models were constructed to examine the all-cause, respiratory and cardiovascular mortality using date of pneumonia onset as baseline with binary pneumonia status as exposure. A total of 2465 men and women (503 cases, 1962 controls) [mean age (s.d.) 64·5 (8·3) years] were included in the study. Between a 30-day to 1-year period, hazard ratios (HRs) of all-cause and cardiovascular mortality were 7·3 [95% confidence interval (CI) 5·4–9·9] and 5·9 (95% CI 3·5–9·7), respectively (with very few respiratory deaths within the same period) in cases compared to controls after adjusting for age, sex, asthma, smoking status, pack years, systolic and diastolic blood pressure, diabetes, physical activity, waist-to-hip ratio, prevalent cardiovascular and respiratory diseases. All outcomes assessed also showed increased risk of death in cases compared to controls after 1 year; respiratory cause of death being the most significant during that period (HR 16·4, 95% CI 8·9–30·1). Hospitalized pneumonia was associated with increased all-cause and specific-cause mortality beyond 30 days.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Aligned, coexisting liquid and solid regions are observed in cw laser annealing of polycrystalline Si films on quartz substrates. These stripe patterns are the precursors of surface topography that exists after cooling. It is proposed that a similar situation exists in the pulse annealing process. A calculation of the temperature evolution which assumes stripe symmetry and kinetic restraints of the crystallization process has been carried out. These calculations indicate a lattice temperature of between 1100 and 1300 K, 10 nsec after the sample has fully solidified.
In this paper we review the current understanding of laser-induced silicon thin film crystal growth on bulk amorphous substrates. We propose a model for oriented nucleation and show that the silicon reflectivity jump on melting coupled with radiant heating lead naturally to this autonucleation mechanism. We then survey various techniques for control of lateral epitaxial growth and conclude with the results of some recent electrical device characterization.
Purpose: The 2007 Institute of Medicine report entitled Emergency Medical Services at the Crossroads identified a need for the establishment of physician subspecialty certification in emergency medical services (EMS). The purpose of this study was to identify and explore the evolution of publications that define the role of the physician in EMS systems in the United States.
Methods: Three comprehensive searches were undertaken to identify articles that define the physician's role in the leadership, clinical development, and practice of EMS. Independent reviewers then evaluated these articles to further determine whether the articles identified the physician's role in EMS. Then, identified articles were classified by the type of publication in order to evaluate the transition from a non-peer reviewed to peer-reviewed literature base and an analysis was performed on the differences in the growth between these two groups. In addition, for the peer-reviewed articles, an analysis was performed to identify the proportion of articles that were quantitative versus qualitative in nature.
Results: The comprehensive review identified 1,504 articles. Ninety articles were excluded due to lack of relevance to the US. The remaining 1,414 articles were reviewed, and 194 papers that address the physician's role within EMS systems were identified; 72 additional articles were identified by hand search of references for a total of 266 articles. The percentage of peer-reviewed articles has increased steadily over the past three decades. In addition, the percentage of quantitative articles increased from the first decade to the second and third decades.
Conclusions: This comprehensive review demonstrates that over the past 30 years an evidence base addressing the role of the physician in EMS has developed. This evidence base has steadily evolved to include a greater proportion of peer-reviewed, quantitative literature.
The autosomal recessive gene, dysgenetic lens (dyl) in the mouse has been mapped on chromosome 4. Two- and three-point crosses involving b (brown) and Mup-1 (Major urinary protein-1) indicate the following gene order: dyl–b–Mup-1. The approximate distance between dyl and b is 12 and between dyl and Mup-1 is 20 cM.
Tropical deforestation is a key contributor to species extinction and climate change, yet the extent of tropical forests and their rate of destruction and degradation through fragmentation remain poorly known. Madagascar's forests are among the most biologically rich and unique in the world but, in spite of longstanding concern about their destruction, past estimates of forest cover and deforestation have varied widely. Analysis of aerial photographs (c. 1953) and Landsat images (c. 1973, c. 1990 and c. 2000) indicates that forest cover decreased by almost 40% from the 1950s to c. 2000, with a reduction in ‘core forest’ > 1 km from a non-forest edge of almost 80%. This forest destruction and degradation threaten thousands of species with extinction. Country-wide coverage of high-resolution validated forest cover and deforestation data enables the precise monitoring of trends in habitat extent and fragmentation critical for assessment of species' conservation status.
Although community-onset bloodstream infection (BSI) is recognized to be a major cause of morbidity and mortality, there is a paucity of population-based studies defining its overall burden. We conducted population-based laboratory surveillance for all community-onset BSI in the Calgary Health Region during 2000–2004. A total of 4467 episodes of community-onset BSI were identified for an overall annual incidence of 81·6/100 000. The three species, Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae were responsible for the majority of community-onset BSI; they occurred at annual rates of 25·8, 13·5, and 10·1/100 000, respectively. Overall 3445/4467 (77%) episodes resulted in hospital admission representing 0·7% of all admissions to major acute care hospitals. The subsequent hospital length of stay was a median of 9 (interquartile range, 5–15) days; the total days of acute hospitalization attributable to community-onset BSI was 51 146 days or 934 days/100 000 annually. Four hundred and sixty patients died in hospital for a case-fatality rate of 13%. Community-onset BSI is common and has a major patient and societal impact. These data support further efforts to reduce the burden of community-onset BSI.
This experiment sought to establish the response to increasing levels of coconut oil (CO) supplementation with a fixed 0·50:0·50 forage:concentrate diet on intake, digestibility and methane (CH4) emissions. Sixteen continental cross beef heifers (mean starting weight 481±36 kg) were assigned randomly to one of four levels of CO; 0 g/day, 125 g/day, 250 g/day or 375 g/day in an incomplete (three periods) multiple (no. =4) Latin-square design experiment (no. =12 per treatment). A linear reduction in CH4 output occurred as the level of CO in the diet increased ( P<0·001) with the greatest reduction at the 375 g/day level (394, 341, 314 and 240 l/day for animals fed 0, 125, 250 and 375 g/day CO, respectively). As the level of CO increased dry-matter (DM) intake (DMI) decreased, however these differences were only statistically significant at the 375 g/day level ( P <0·001). The proportional reduction in CH4 output was greater than the proportional reduction in DMI and hence CH4 l/kg DMI decreased from 39·8 l/kg when no CO was given to 29·7 l/kg when 375 g/day CO was given. The addition of CO to the diet resulted in a significant decline in dry-matter digestibility (DMD) at the 375 g/day level (P<0·05). These data demonstrate that the inclusion of CO at levels from 0·013 to 0·045 of the dietary DM within a 0·50:0·50 silage and concentrate ration reduces CH4 production with no adverse effect on DMI or DMD up to the 250 g/day level (0·027 of dietary DM).
Objectives: The aim of this study was to assess the impact on implant survival, abutment skin reaction and patient satisfaction in patients implanted with a bone-anchored hearing aid (BAHA), following the introduction of a multidisciplinary team (MDT) in 1997.
Design and methods: Part prospective and retrospective analysis. Implant survival and cause of failures were recorded along with abutment skin reaction (graded as none, mild, moderate and severe, according to the amount of wound care required). Patient satisfaction and quality of life were assessed using a questionnaire enquiring about several aspects of the use and benefits of their BAHA.
Setting and participants: Eighty patients treated at the Bradford Royal Infirmary between 1991 and 2005. The unit is a recognized tertiary referral centre.
Results and conclusions: Twelve out of 80 implants failed, giving an overall failure rate of 15 per cent. Kaplan–Meier survival curves show a steady decrease in implant survival. The MDT had a positive effect on implant survival and adverse skin reactions, with a higher proportion of patients experiencing no reaction after its introduction. There was a 92.5 per cent response rate to the questionnaire. Overall patient satisfaction was high, both before and after the introduction of the MDT.