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The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.
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.
Canopy-forming fucoid algae have an important role as ecosystem engineers on rocky intertidal shores, where they increase the abundance of species otherwise limited by exposure during low tide. The facilitative relationship between Ascophyllum nodosum and associated organisms was explored using a frond breakage experiment (100%, 50%, 25%, 0% intact-frond treatments) in southern England, to assess the consequences of disturbance. Understorey substratum temperature was on average 3°C higher in 0% and 25% intact-frond treatments than in plots with 50% and 100% intact fronds. Light (as PAR during low tide) doubled in 0% intact-frond treatments in comparison to other treatments (which had similar light levels). Mobile invertebrate species richness declined by on average 1 species per m2 in the treatments with only 25% and 0% intact fronds, and the abundance of Littorina obtusata declined by 2.4–4.2 individuals per m2 in the treatments with 25 and 0% intact fronds. Sessile taxa, including Osmundea pinnatifida and encrusting coralline algae, declined by half on average in the 0% intact-frond treatment. These results suggest that the ability of Ascophyllum to mediate environmental conditions to the understorey is the mechanism responsible for species distributed in the understorey (autogenic ecosystem engineering). The results of this study imply that a pulse disturbance resulting in a 50% breakage of Ascophyllum fronds significantly increases temperature and decreases the abundance of mobile invertebrates usually associated with Ascophyllum. Sessile taxa associated with Ascophyllum can, however, withstand disturbances down to 25% intact Ascophyllum fronds.
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 UBVRI photometry of the faint and highly erratic cataclysmic variable discovered by Hawkins (1983) from a sequence of U.K. Schmidt plates. Observations using the ANU 2.3 m telescope over two nights in September 1986 show pronounced and repeatable modulation at a binary period of 108.6 min. Dramatic colour differences are evident in the folded UBVRI light curves: in the U band, a single sinusoidal peak is present, while at longer wavelengths, a second red peak dominates at a phase separation of Δϕ = 0.5. This behaviour is strongly suggestive of cyclotron emission from two magnetic accretion funnels in an AM Herculis binary system. Furthermore, the binary period lies in the narrow range of 100-115 minutes that characterizes most of the AM Herculis variables lying on the short side of the 2-3 hour period gap. We conclude therefore that the object is almost certainly a new AM Herculis system, and develop a model in which the blue and red components originate from two non-diametrically opposed cyclotron regions that are characterized by differing electron temperatures and opacities. Predictions are made regarding the linear and circular polarization properties of this important new magnetic variable.
We have undertaken a study of the 3-D spatial distribution of the older (τ ≥ 1–2 Gyr) stellar population lying beyond ~ 2 kpc in projected radial distance from the centre of the SMC. The study will eventually cover 120 square degrees including six overlapping Schmidt fields. Here we present the results from an area of 80 square degrees including the western, northern and north-eastern outer parts of the SMC.
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.
We review an optofluidic waveguiding lab-on-a-chip used to sense bioparticles. The sensor uses a liquid filled Anti-Resonant Reflecting Optical Waveguide (ARROW) that is interfaced with standard ridge waveguides. The ridge waveguides are coupled to off-chip lasers and detectors via optical fiber. A perpendicular intersection between the ARROW and a ridge waveguide is especially useful for detecting fluorescently tagged particles. Light coupled into the ridge waveguide can fluorescently excite these particles within a very small volume. Fluorescent signal can then be guided within the ARROW and subsequently off chip to a detector.
We also discuss how such devices are fabricated. Both the ARROW and ridge waveguides are made using alternating thin films of tantalum oxide and silicon dioxide on silicon substrates. These thin films are deposited by either sputtering or plasma enhanced chemical vapor deposition (PECVD). The waveguides are patterned using a combination of standard photolithographic processes, reactive ion etching, and sacrificial etching. Low-loss optical guiding is very dependent on both the waveguide structure and the materials used. The latest processes for maximizing detection sensitivity are reviewed.
We also present results using the optofluidic waveguiding sensor for detecting a variety of different types of particles such as fluorescently labeled nanobeads, viruses, ribosomes, and RNA.
Uncertainties exist regarding the population risks of hospitalization due to pandemic influenza A(H1N1). Understanding these risks is important for patients, clinicians and policy makers. This study aimed to clarify these uncertainties. A national surveillance system was established for patients hospitalized with laboratory-confirmed pandemic influenza A(H1N1) in England. Information was captured on demographics, pre-existing conditions, treatment and outcomes. The relative risks of hospitalization associated with pre-existing conditions were estimated by combining the captured data with population prevalence estimates. A total of 2416 hospitalizations were reported up to 6 January 2010. Within the population, 4·7 people/100 000 were hospitalized with pandemic influenza A(H1N1). The estimated hospitalization rate of cases showed a U-shaped distribution with age. Chronic kidney disease, chronic neurological disease, chronic respiratory disease and immunosuppression were each associated with a 10- to 20-fold increased risk of hospitalization. Patients who received antiviral medication within 48 h of symptom onset were less likely to be admitted to critical care than those who received them after this time (adjusted odds ratio 0·64, 95% confidence interval 0·44–0·94, P=0·024). In England the risk of hospitalization with pandemic influenza A(H1N1) has been concentrated in the young and those with pre-existing conditions. By quantifying these risks, this study will prove useful in planning for the next winter in the northern and southern hemispheres, and for future pandemics.
The new Core-XAS (X-ray absorption spectroscopy) beamline (B18) at Diamond aims to provide a reliable spectrometer for a broad scientific community. With this in mind, B18 has been built as a general-purpose beamline and offers to users a variety of sample environments and detection methods. Here we will present the first commissioning results and some of the capabilities of this versatile instrument.
During the past decade, the number known shallow-amplitude, yet totally eclipsing, extreme-mass-ratio binaries has increased from one (AW UMa, which is now in doubt) to about a dozen. Statistics are accumulating that will tell us the nature of these once rare systems. These individual interacting field binaries are believed to be the progenitors of FK Comae-type fast-rotating subgiants, which are similar to the cluster stars called ‘variable blue stragglers.’ We review our recent observations and new analyses of the individual systems, V409 Hya, GSC 1283 0053 Ori, GSC 2537 520 CVn, using the 2007 Wilson Code and summarize results from our previous observations (V802 Aql, V902 Sgr) and those from the literature (e.g., CK Boo, GR Vir, HV Aqr, UY UMa, EM Pis, CU Tau, TV Mus) to disclose a preliminary picture of the character of this interesting class of binary stars.
We have found photometric indications that Interacting Eclipsing Binaries of early to mid F spectral type (and possibly A) have strong magnetic activity which would arise from convective atmospheres. Light curve solutions and periodicity studies revealing spots, magnetic breaking and magnetic cycles are presented in XZ CMi, V965 Cyg and V963 Cyg.
We are conducting a survey of the southern sky to study the properties of the lowest mass stars and the sub-stellar brown dwarf population thought to exist at masses below 0.08 M⊙. The survey makes use of plates from the UK and ESO Schmidt telescopes, using the new SuperCOSMOS plate measuring machine at Edinburgh to provide a catalogue of photographic BRI colours and proper motion measurements. Candidates are selected by extreme R–I colour (> 2.5) to a plate-limited magnitude of I ≈ 19.0 and R ≈ 21.0. The size of the survey is only limited by the progress of the UK Schmidt I band survey and the availability of photometric data for calibration of SuperCOSMOS measurements. It is anticipated that the survey will form part of a multi-colour proper motion database of southern sky objects.
Soil erosion is a major environmental problem that threatens world food production (UNEP, 1980; Dudal, 1981; Kovda, 1983). In the world today not only is the total population being fed greater than ever before in history, but more humans are malnourished (Swaminathan, 1983). At present, one thousand million people are malnourished and the problem is growing rapidly in severity (Latham, 1984). Many changes have occurred since the early 1900s when most nations were self-sufficient in food. Today, the great majority of the world's 183 nations are major food importers (FAO, 1983), underscoring a growing disparity in food resources (Swaminathan, 1983). The food supply problem has persisted, ‘and in some cases worsened despite an increased pace of development’ (Latham, 1984). Given these ominous trends, the control of soil erosion for a sustainable agricultural system is essential to any program to improve world food security and development.
Adequate food supplies depend on productive land. At present 97% of the food supply comes from land and only 3% from the oceans and other aquatic systems (CEQ, 1980). Hence, we must safeguard the productivity of the land to feed the ever-increasing world population. Just at a time when agricultural efforts are focused on increasing crop yields, land degradation is increasing throughout the world. Global dimensions of land destruction are alarming. About 35% of the earth's land surface is affected (Mabbutt, 1984).
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.
We present preliminary results from a study of the radial velocities of red horizontal branch stars in the north-eastern outer parts of the Small Magellanic Cloud (SMC). The sample is located in an area with a large line-of-sight depth of 15 kpc. It is suggested that there is a correlation between line-of-sight distance and radial velocity for these stars, with the more distant ones showing significantly higher velocities.