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We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
The use of duration models in political science continues to grow, more than a decade after Box-Steffensmeier and Jones (2004). However, several common misconceptions about the models still persist. To improve scholars’ use and interpretation of duration models, we point out that they are a type of regression model and therefore follow the same rules as other more commonly used regression models. In this article, we present four maxims as guidelines. We survey the various duration model interpretation strategies and group them into four categories, which is an important organizational exercise that does not appear elsewhere. We then discuss the strengths and weaknesses of these strategies, noting that all are correct from a technical perspective. However, some strategies make more sense than others for nontechnical reasons, which ultimately informs best practices.
The investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host–parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.
Introduction: Residency training takes place in a work-place learning environment. Residents may work with several supervisors over the course of their training and each will provide feedback and assessments to them. Each supervisor may have a different approach to the delivery of their feedback and may deliver different assessments for the same quality of performance. Research question: among residents who receive regular feedback how do different styles of feedback by supervisors impact the residents’ learning? Methods: A qualitative methodology was used. Participants were residents from residency programs that have routine one-on-one feedback and assessment. In depth, semi-structured one-on-one interviews were conducted by the primary investigator (PI). These were then transcribed, reviewed and coded. The participants were University of Toronto and McMaster University residents. Sample size will be determined by thematic saturation and data collection is ongoing. The interview guide was updated in an iterative fashion to further explore themes generated in the initial interviews. Interview transcripts will be reviewed and coded by the PI with assistance from collaborators with qualitative methodological expertise. Results: Analysis of the first six participants revealed five themes. Residents described remembering feedback that generated a strong emotional response, both positive and negative; reflection on feedback as a component of using it for learning was consistent; issues with reconciling feedback received that was in conflict with previously feedback; relationship with the individual providing the feedback impacted feedback interpretation; feedback was parsed by residents to determine the rationale of the assessor and whether to incorporate feedback into learning process. Conclusion: How residents use feedback to further their learning is variable. This study identifies that styles of feedback, emotional response and relationship with the provider are all contributors to the learning that occurs after a feedback encounter. It also identifies that residents reflect on feedback differently and make decisions about how to incorporate feedback into their learning and practice. The individuality of these responses to feedback are important for trainee self-reflection in furthering their learning as well as important in faculty development as they develop skills in assessment and feedback. It is also important for training programs that facilitate the trainee supervisor interactions.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
The use of the Polychromator (multichannel spectrometer) for X-ray analysis allows choice of the optimum combination of slit width, crystal type, focussing circle radius and detector for each of the elements to be determined by the instrument.
Comparisons will be made of various curved and ground crystals such as quartz, lithium fluoride, sodium chloride and ADP used in a focussing spectrometer. The effect of the width of the entrance and exit slits upon resolution, line intensity and line-to-background ratios will be discussed. Gas filled detectors such as Multitrons, flow proportional counters and Geiger counters will be discussed as to the effect of the filling upon efficiency and upon their use with counting or integrating techniques. Limits of detectability for various elements with optimum combinations of the above components will be reported.
We are engaged in a study of the ash produced by combustion of lignite in a 750-MW power station. The aim is to follow the transport of elements with Z> 16 from the mine, through: a) the combustion process, b) emissionto the atmosphere or c) deposition in a land fill, d) transport in the environment and e) subsequent uptake by animals and humans. The resulting data will be used to estimate potential adverse impact on human health caused by operation of the power station.
X-ray microscopy is a field that has developed rapidly in recent years. Two different approaches have been used. Zone plates have been employed to produce focussed beams with sizes as low as 0.07 pm for x-ray energies below 1 keV. Images of biological materials and elemental maps for major and minor low Z have been produced using above and below absorption edge differences. At higher energies collimators and focussing mirrors have been used to make small diameter beams for excitation of characteristic K— or L-x rays of all elements in the periodic
Several grass and broadleaf weed species around the world have evolved multiple-herbicide resistance at alarmingly increasing rates. Research on the biochemical and molecular resistance mechanisms of multiple-resistant weed populations indicate a prevalence of herbicide metabolism catalyzed by enzyme systems such as cytochrome P450 monooxygenases and glutathione S-transferases and, to a lesser extent, by glucosyl transferases. A symposium was conducted to gain an understanding of the current state of research on metabolic resistance mechanisms in weed species that pose major management problems around the world. These topics, as well as future directions of investigations that were identified in the symposium, are summarized herein. In addition, the latest information on selected topics such as the role of safeners in inducing crop tolerance to herbicides, selectivity to clomazone, glyphosate metabolism in crops and weeds, and bioactivation of natural molecules is reviewed.
The experience of obsessive-compulsive disorder (OCD) symptoms that have a religious theme is common. Recent research has found that religious participants with religious OCD symptoms frequently turn to religious advisors, such as imams or clergy, for help to understand and alleviate their symptoms. As such, the advice provided by imams or clergy may have an important impact on the response of the person seeking help. This study examined the attitudes, beliefs and experiences of 64 Muslim imams with mosque-goers who had religious OCD symptoms, particularly scrupulosity. This study also examined imams’ familiarity with first-line psychological treatments for OCD such as Exposure and Response Prevention (ERP). Sunni imams from Australia and Shia imams from Iran completed an online survey based on the research of Deacon, Vincent, and Zhang (2012), which was conducted with Christian clergy in the United States. Results showed that the majority of imams were unfamiliar with scrupulosity as a possible symptom of a mental health problem, such as OCD, and with ERP as a recognised treatment for OCD. While 37% of participants reported having been approached by mosque-goers for help with scrupulosity, only 9% referred mosque-goers to mental health professionals, and only one imam reported having referred a mosque-goer for ERP. Sunni imams located in Australia were more likely to provide advice inconsistent with the ERP approach and were also significantly less likely than Shia imams located in Iran to recommend referral to a mental health professional who was not affiliated with their own religious denomination. Finally, Sunni imams had significantly higher scores than Shia imams on Thought Action Fusion (TAF) subscales. Results of multiple regression analysis revealed that TAF explained a considerable amount of the variance related to ERP-inconsistent advice. Research implications and limitations are discussed.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
It is well established that dicamba can cause severe injury to soybean that is not resistant to dicamba. Dicamba-resistant (DR) cotton became available in 2015, followed by DR soybean in 2016; in late 2016 came the release of new dicamba formulations approved for topical use in cotton and soybeans. Until this approval, use of dicamba was limited to primarily corn, small grains, range and pasture, and eco-fallow acres. Hence, studies were conducted in 2015 and 2016 to examine off-target movement of two dicamba formulations using non-DR soybean as a bio-indicator. Diglycolamine (DGA) and N,N-Bis(3-aminopropyl)methylamine (BAPMA) dicamba were applied simultaneously at 560 g ae ha–1 in the center of two side-by-side 8-ha fields to vegetative glufosinate-resistant soybean. On the same day, a rate response experiment was established encompassing nine different dicamba rates of each formulation. Results from the rate response experiment indicate that soybean is equally sensitive to DGA and BAPMA dicamba. In 2015, a rain event occurring 6 to 8 h after application of the large drift trial probably limited off-target movement by incorporating some of the herbicide into the soil. As a result, secondary drift was less in 2015 than in 2016. However, minimal secondary injury (<5%) occurred 12 m farther into DGA dicamba plots in 2015. In 2016, secondary movement was decreased by 72 m when BAPMA dicamba was used compared to DGA dicamba. Appreciable secondary movement of both DGA and BAPMA dicamba is possible following in-crop applications of either formulated product to soybean in early to mid-summer. Additionally, the risk for secondary movement of BAPMA dicamba is slightly less than for DGA dicamba.
In the occurrence of dicamba drift, it is not well understood what measurements from soybean plants would correlate with damage to soybean offspring; therefore, possible relationships are of great interest. Sixteen drift trials were established in 2014 and 2015 at the Northeast Research and Extension Center in Keiser, AR. A single 8-m-wide by 30- or 60-m-long pass with a high-clearance sprayer was made in each soybean field, resulting in a dicamba drift event. Seeds were collected from plants in each drift trial and planted in the field in 2015 and 2016. Data were subjected to correlation analysis to determine pairwise associations among parent and offspring observations. Auxin-like symptomology in offspring consistent with dicamba, primarily as leaf cupping, appeared in plots at the unifoliate and first trifoliate stages. Auxin-like symptoms were more prevalent in offspring collected from plants from later reproductive stages as opposed to early reproductive stages. The highest correlation coefficients occurred when parent plants were treated at the R5 growth stage. Parent mature pod malformation was correlated with offspring emergence (r=−0.37, P=0.0082), vigor (r=−0.57, P ≤ 0.0001), injury (r=0.93, P ≤ 0.0001), and percent of plants injured (r=0.92, P ≤ 0.0001). This research documents that soybean damaged from dicamba drift during the R1 to R6 growth stages can negatively affect offspring and that occurrence of pod malformation after dicamba drift at the R5 growth stage may be indicative of injury to the offspring.
We consider the stability of nonlinear travelling waves in a class of activator-inhibitor systems. The eigenvalue equation arising from linearizing about the wave is seen to preserve the manifold of Lagrangian planes for a nonstandard symplectic form. This allows us to define a Maslov index for the wave corresponding to the spatial evolution of the unstable bundle. We formulate the Evans function for the eigenvalue problem and show that the parity of the Maslov index determines the sign of the derivative of the Evans function at the origin. The connection between the Evans function and the Maslov index is established by a ‘detection form,’ which identifies conjugate points for the curve of Lagrangian planes.
Soybean with resistance to dicamba (DR soybean) and glyphosate and cotton with resistance to glyphosate, glufosinate, and dicamba were recently commercialized in the United States and have been readily adopted. To evaluate results of over-the-top application of dicamba in DR crops, field studies were designed to examine off-target movement using proposed sprayer setup recommendations. Association analysis and nonlinear regression techniques were used to examine the effects of 26 field-scale drift trials conducted in 2014 and 2015 during soybean reproductive development (R1 through R6). The greatest predictors (injury, height reduction) of soybean yield reduction generally occurred and had steeper relationships after drift events at the R1 growth stage than at later stages. Using non-DR soybean as an indicator, dicamba was documented to move as much as 152 m from the application area (distance to 5% injury). Instances of height reduction (5%) differed among growth stages, with the greatest distance occurring at R1 (83.4 m). Soybean yield reduction was erratic, with the greatest distance to 5% loss in yield occurring at 42.8 m after an R1 drift event. Overall, the data suggest flowering-stage soybean is more sensitive than later reproductive soybean to injury, height reductions, and yield loss. Average and maximum wind speeds did not account for the injury documented from dicamba, and it is hypothesized that other meteorological variables also play a notable role in dicamba off-target movement as well as growing conditions following exposure. With concerns surrounding off-target movement of dicamba, proper stewardship of this new technology will be key to its longevity.
During the 2014–2016 Ebola outbreak, health services in Liberia collapsed. Health care facilities could not support effective infection prevention and control (IPC) practices to prevent Ebola virus disease (EVD) transmission necessitating their closure. This report describes the process by which health services and infrastructure were recovered in the public hospital in Monrovia, Liberia. The authors conducted an assessment of the existing capacity for health care provision, including qualitative interviews with community members, record reviews in Ebola treatment units, and phone calls to health facilities. Assessment information was used to determine necessary actions to re-establish services, including building and environmental renovations, acquiring IPC supplies, changing health care practices, hiring additional staff, developing and using an EVD screening tool, and implementing psychosocial supports. On-site monitoring was continued for 2 years to assess what changes were sustained. Described in the report are 2 cases that highlight the challenge of safely re-establishing services with only a symptom-based screening tool and no laboratory tests available on-site. Despite fears among the public, health workers, and the international community, the actions taken enabled basic health care services to be provided during EVD transmission and led to sustainable improvements. This experience suggests that providing routine medical needs helps limit the morbidity and mortality during times of disease outbreak. (Disaster Med Public Health Preparedness. 2018;13:767–773)