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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
Barton Peninsula is an ice-free area located in the southwest corner of King George Island (South Shetland Islands, Antarctica). Following the Last Glacial Maximum, several geomorphological features developed in newly exposed ice-free terrain and their distribution provide insights about past environmental evolution of the area. Three moraine systems are indicative of three main glacial phases within the long-term glacial retreat, which also favoured the development of numerous lakes. Five of these lakes were cored to understand in greater detail the pattern of deglaciation through the study of lacustrine records. Radiocarbon dates from basal lacustrine sediments enabled the reconstruction of the chronology of Holocene glacial retreat. Tephra layers present in lake sediments provided additional independent age constraints on environmental changes based on geochemical and geochronological correlation with Deception Island-derived tephra. Shrinking of the Collins Glacier exposed the southern coastal fringe of Barton Peninsula at 8 cal ky BP. After a period of relative stability during the mid-Holocene, the ice cap started retreating northwards after 3.7 cal ky BP, confining some glaciers within valleys as shown by moraine systems. Lake sediments confirm a period of relative glacial stability during the last 2.4 cal ky BP.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Takotsubo cardiomyopathy is characterised by akinesis and ballooning of the left ventricular apex during contraction of the otherwise normal base of the heart. We describe the case of a 7-month-old previously healthy female who presented with an unwitnessed cardiac arrest. Workup raised suspicion for non-accidental trauma. Despite progression to brain death, the severely decreased ventricular function and apical akinesis of the left ventricle improved within 40 hours of admission. This report will familiarise paediatricians with this rare cardiomyopathy and emphasise the importance of considering non-accidental trauma as an inciting event for patients with unwitnessed cardiac arrest found to have decreased ventricular function.
This work combines very detailed measurements from terrestrial laser scanner (TLS), ground-based interferometry radar (GB-SAR) and ground-penetrating radar (GPR) to diagnose current conditions and to analyse the recent evolution of the Monte Perdido Glacier in the Spanish Pyrenees from 2011 to 2017. Thus, this is currently one of the best monitored small glacier (<0.5 km2) worldwide. The evolution of the glacier surface was surveyed with a TLS evidencing an important decline of 6.1 ± 0.3 m on average, with ice losses mainly concentrated over 3 years (2012, 2015 and 2017). Ice loss is unevenly distributed throughout the study period, with 10–15 m thinning in some areas while unchanged areas in others. GB-SAR revealed that areas with higher ice losses are those that are currently with no or very low ice motion. In contrast, sectors located beneath the areas with less ice loss are those that still exhibit noticeable ice movement (average 2–4.5 cm d─1 in summer, and annual movement of 9.98 ma─1 from ablation stakes data). GPR informed that ice thickness was generally <30 m, though locally 30–50 m. Glacier thinning is still accelerating and will lead to extinction of the glacier over the next 50 years.
Supplementation with copper (Cu) improves deer antler characteristics, but it could modify meat quality and increase its Cu content to levels potentially harmful for humans. Here, we studied the effects of Cu bolus supplementation by means on quality and composition of sternocephalicus (ST) and rectus abdominis (RA) muscles (n=13 for each one) from yearling male red deer fed with a balanced diet. Each intraruminal bolus, containing 3.4 g of Cu, was administered orally in the treatment group to compare with the control group. Meat traits studied were pH at 24 h postmortem (pH24), colour, chemical composition, cholesterol content, fatty acid (FA) composition, amino acid (AA) profile and mineral content. In addition, the effect of Cu supplementation on mineral composition of liver and serum (at 0 and 90 days of treatment) was analysed. No interactions between Cu supplementation and muscle were observed for any trait. Supplementation with Cu increased the protein content of meat (P<0.01). However, Cu content of meat, liver and serum was not modified by supplementation. In fact, Cu content of meat (1.20 and 1.34 mg/kg for Cu supplemented and control deer, respectively) was much lower in both groups than 5 mg/kg of fresh weight allowed legally for food of animal origin. However, bolus of Cu tended to increase the meat content of zinc and significantly increased (P<0.05) the hepatic contents of sodium and lead. Muscles studied had different composition and characteristics. The RA muscle had significantly higher protein content (P<0.001), monounsaturated FA content (P<0.05) and essential/non-essential AA ratio (P<0.01) but lower pH24 (P<0.01) and polyunsaturated FA content (P=0.001) than the ST muscle. In addition, RA muscle had 14.4% less cholesterol (P=0.001) than ST muscle. Also, mineral profile differed between muscles with higher content of iron, significantly higher (P<0.001) content of zinc and lower content of calcium, magnesium and phosphorus (P<0.05) for ST muscle compared with RA. Therefore, supplementation with Cu modified deer meat characteristics, but it did not increase its concentration to toxic levels, making it a safe practice from this perspective. Despite the lower content of polyunsaturated FA, quality was better for RA than for ST muscle based on its higher content of protein with more essential/non-essential AA ratio and lower pH24 and cholesterol content.
Outbreaks of Old World cutaneous leishmaniasis (CL) have significantly increased due to the conflicts in the Middle East, with most of the cases occurring in resource-limited areas such as refugee settlements. The standard methods of diagnosis include microscopy and parasite culture, which have several limitations. To address the growing need for a CL diagnostic that can be field applicable, we have identified five candidate neoglycoproteins (NGPs): Galα (NGP3B), Galα(1,3)Galα (NGP17B), Galα(1,3)Galβ (NGP9B), Galα(1,6)[Galα(1,2)]Galβ (NGP11B), and Galα(1,3)Galβ(1,4)Glcβ (NGP1B) that are differentially recognized in sera from individuals with Leishmania major infection as compared with sera from heterologous controls. These candidates contain terminal, non-reducing α-galactopyranosyl (α-Gal) residues, which are known potent immunogens to humans. Logistic regression models found that NGP3B retained the best diagnostic potential (area under the curve from receiver-operating characteristic curve = 0.8). Our data add to the growing body of work demonstrating the exploitability of the human anti-α-Gal response in CL diagnosis.
For most patients, adenoviruses cause few acute health concerns and are often self-limiting. Patients who are immunocompromised or immunosuppressed, however, are at risk for disseminated adenovirus and suffer high morbidity and mortality, without well-defined treatment options. We report the case of a 9-month-old boy who was successfully treated for disseminated adenovirus infection with intravenous immunoglobulin and cidofovir 3 months post heart transplant, tailored to serum adenoviral load and clinical response. We emphasise the importance of early identification, monitoring, and a potentially novel treatment in the paediatric cardiac transplant population with disseminated adenovirus infection.
The purpose of this work was to evaluate the capacity of existing landscape irrigation equipment to deliver the expected irrigation depth at a level of uniformity that can potentially be used in a precision irrigation management environment. Popular pop-up sprayer systems from two leading manufacturers (Rain-bird and Hunter variable arc and fixed arc nozzles) were subject to spatial distribution tests, in order to establish the application patterns under ideal conditions. The results indicate that it is not possible to fully rely on the catalog application depth values, with some variable arc nozzles applying up to 200% of the catalog values. These nozzles can have low values of uniformity, with Christiansen´s uniformity coefficient, CU, of between 0.31 and 0.70, making it difficult to obtain good uniformity even under a back-to-back setting. These results indicate that variable arc nozzles are not recommended for use in precision agriculture. It is preferable to use fixed arc nozzles, after actual field evaluation.
The main objective of this work was to evaluate technologies that have potential for monitoring aspects related to spatial and temporal variability of soil nutrients and pasture yield and for support to decision making by the farmers. Three types of sensors were evaluated: an electromagnetic induction sensor, an active optical sensor and a capacitance probe. The results are relevant for the selection of the adequate sensing system for each particular application and to open new perspectives for other works that would allow the testing, calibration and validation of the sensors in a wider range of pasture production conditions and rainfall patterns, characteristic of the Mediterranean region.
The main factors affecting the mechanical (and other) properties of bone, including antler, are the proportions of ash (especially Ca and P) and collagen content. However, some trace minerals may also play more important roles than would be expected, given their low levels in bone and antler. One such trace mineral is Cu. Here, we studied the effects of Cu supplementation on the mechanical and structural characteristics, and mineral content of antlers from yearling and adult (4 years of age) red deer fed a balanced diet. Deer (n=35) of different ages (21 yearlings and 14 adults) were studied. A total of 18 stags (11 yearlings and 7 adults) were injected with Cu (0.83 mg Cu/kg BW) every 42 days, whereas the remaining 17 (10 yearlings and 7 adults) were injected with physiological saline solution (control group). The Cu content of serum was analysed at the beginning of the trial and 84 days after the first injection to assess whether the injected Cu was mobilized in blood. Also, the mechanical and structural properties of antlers and the mineral content in their cortical walls were examined at three (yearlings) or four (adults) points along the antler beam. The effect of Cu supplementation was different in yearlings and adults. In yearlings, supplementation increased the Cu content of serum by 28%, but did not affect antler properties. However, in adults, Cu supplementation increased the Cu content of serum by 38% and tended to increase the cortical thickness of antlers (P=0.06). Therefore, we conclude that, even in animals receiving balanced diets, supplementation with Cu could increase antler cortical thickness in adult deer, although not in yearlings. This may improve the trophy value of antlers, as well as having potential implications for bones in elderly humans, should Cu supplementation have similar effects on bones as those observed in antlers.
We propose a taxonomic revision of the dixenous trypanosomatids currently classified as Endotrypanum and Leishmania, including parasites that do not fall within the subgenera L. (Leishmania) and L. (Viannia) related to human leishmaniasis or L. (Sauroleishmania) formed by leishmanias of lizards: L. colombiensis, L. equatorensis, L. herreri, L. hertigi, L. deanei, L. enriettii and L. martiniquensis. The comparison of these species with newly characterized isolates from sloths, porcupines and phlebotomines from central and South America unveiled new genera and subgenera supported by past (RNA PolII gene) and present (V7V8 SSU rRNA, Hsp70 and gGAPDH) phylogenetic analyses of the organisms. The genus Endotrypanum is restricted to Central and South America, comprising isolates from sloths and transmitted by phlebotomines that sporadically infect humans. This genus is the closest to the new genus Porcisia proposed to accommodate the Neotropical porcupine parasites originally described as L. hertigi and L. deanei. A new subgenus Leishmania (Mundinia) is created for the L. enriettii complex that includes L. martiniquensis. The new genus Zelonia harbours trypanosomatids from Neotropical hemipterans placed at the edge of the Leishmania–Endotrypanum-Porcisia clade. Finally, attention is drawn to the status of L. siamensis and L. australiensis as nomem nudums.
Our knowledge of the diversity, ecology, and phylogeny of Mesozoic birds has increased significantly during recent decades, yet our understanding of their flight competence remains poor. Wing loading (WL) and aspect ratio (AR) are two aerodynamically relevant parameters, as they relate to energy costs of aerial locomotion and flight maneuverability. They can be calculated in living birds (i.e., Neornithes) from body mass (BM), wingspan (B), and lift surface (SL). However, the estimates for extinct birds can be subject to biases from statistical issues, phylogeny, locomotor adaptations, and diagenetic compaction. Here we develop a sequential approach for generating reliable multivariate models that allow estimation of measurements necessary to determine WL and AR in the main clades of non-neornithine Mesozoic birds. The strength of our predictions is supported by the use of those variables that show similar scaling patterns in modern and stem taxa (i.e., non-neornithine birds) and the similarity of our predictions with measurements obtained from fossils preserving wing outlines. In addition, although our WL and AR values are based on estimates (BM, B, and SL) that have an associated error, there is no cumulative error in their calculation, and both parameters show low prediction errors. Therefore, we present the first taxonomically broad, error-calibrated estimation of these two important aerodynamic parameters in non-neornithine birds. Such estimates show that the WL and AR of the non-neornithine birds here analyzed fall within the range of variation of modern birds (i.e., Neornithes). Our results indicate that most modern flight modes (e.g., continuous flapping, flap and gliding, flap and bounding, thermal soaring) were possible for the wide range of non-neornithine avian taxa; we found no evidence for the presence of dynamic soaring among these early birds.
Urban slum environments in the tropics are conducive to the proliferation and the spread of rodent-borne zoonotic pathogens to humans. Calodium hepaticum (Brancroft, 1893) is a zoonotic nematode known to infect a variety of mammalian hosts, including humans. Norway rats (Rattus norvegicus) are considered the most important mammalian host of C. hepaticum and are therefore a potentially useful species to inform estimates of the risk to humans living in urban slum environments. There is a lack of studies systematically evaluating the role of demographic and environmental factors that influence both carriage and intensity of infection of C. hepaticum in rodents from urban slum areas within tropical regions. Carriage and the intensity of infection of C. hepaticum were studied in 402 Norway rats over a 2-year period in an urban slum in Salvador, Brazil. Overall, prevalence in Norway rats was 83% (337/402). Independent risk factors for C. hepaticum carriage in R. norvegicus were age and valley of capture. Of those infected the proportion with gross liver involvement (i.e. >75% of the liver affected, a proxy for a high level intensity of infection), was low (8%, 26/337). Sixty soil samples were collected from ten locations to estimate levels of environmental contamination and provide information on the potential risk to humans of contracting C. hepaticum from the environment. Sixty percent (6/10) of the sites were contaminated with C. hepaticum. High carriage levels of C. hepaticum within Norway rats and sub-standard living conditions within slum areas may increase the risk to humans of exposure to the infective eggs of C. hepaticum. This study supports the need for further studies to assess whether humans are becoming infected within this community and whether C. hepaticum is posing a significant risk to human health.
We have taken deep R-band images of fields around five radiogalaxies: 0956+47, 1217+36, 3C256, 3C324 and 3C294 with 1 < z < 2. We found a statistically significant excess of bright (19.5 < R < 22) galaxies on scales of 2 arcmin around the radiogalaxies. The excess has been determined empirically to be at ≳99.5% level. It is remarkable that this excess is not present for 22 < R < 23.75 galaxies within the same area, suggesting that the excess is not physically associated to the galaxies but due to intervening groups and then related to gravitational lensing.
We present results of the optical identification of a spatially complete, flux limited sample of about 700 ROSAT All-Sky X-ray sources contained in 6 study areas north of δ = −9° with |bII|> 20° (including one region near the North Galactic pole (NGP), another one near the North Ecliptic pole (NEP)). Countrate limits are 0.01 cts s–1 near the NEP and 0.03 cts s–1 for the other areas. The optical observations were performed at the 2.15-m telescope of the Guillermo Haro Observatory, Mexico, using the Landessterwarte Faint Object Spectrograph Camera which allows to carry out direct CCD imaging and multi-object spectroscopy. The limiting magnitude is about 19m for spectroscopy and about 23m for B and R direct imaging. Our analysis shows a dependency of the ratio of ‘extragalactic’ (e.g., AGN, cluster of galaxies) to ‘stellar’ (e.g., coronal emitters, active binaries) counterparts on NH. In the area near the NGP (low NH) ‘extragalactic’ counterparts dominate, while in the area with the highest NH ‘stellar’ counterparts dominate.
We have carried out optical spectroscopic observations at intermediate spectral resolution of the massive high redshift radio galaxy 0902+34 at z ≈ 3.39. This source was first identified by Lilly (1988) (from hereafter L88). The study of high redshift radio galaxies is interesting to analyze the physical conditions of the early universe and the galaxy evolution at cosmological redshifts. It has been claimed that some of these systems may be protogalaxies in the process of formation. Indications for this are the flat spectrum and the absence of the 4000 Å break, features which have already been observed in many cases. In particular, observations in the spectral range from V to K suggest that 0902+34 is a young galaxy (Eisenhardt and Dickinson 1992). Recent radio observations of the 21 cm line of neutral hydrogen have detected (Uson et al. 1991) an absorption against the radio continuum source. This absorption could also leave a track in the optical, redwards the Lyα line. Our observations were carried out with the ISIS spectrograph at the 4.2 m William Herschel Telescope (seeing ≈ 1.2–1.6 arcsec). A spectral dispersion of 0.78 Å/pixel (blue arm) and 1.38 Å/pixel (red arm) was obtained. Å long slit of width 3′ was used providing a spectral resolution of ≈ 5.4 Å in the blue arm and of ≈ 9.5 Å in the red one. Both resolutions are a clear improvement over that achieved by L88 of 20 Å, allowing us to resolve the Lyα line (and its possible structure) and any other possible strong features appearing in the spectral range observed (e. g., C iv λ1549, He ii λ1640, …). Six different observations of 2700 s of the radio galaxy 0902+34 were carried out. The slit was rotated to coincide with the parallactic angle at the beginning of each exposure. This will allow us to map spectroscopically different regions of the galaxy (for more details see Martín-Mirones et al. 1994).
Emergency Medical Service (EMS) systems are vital in the identification, assessment, and treatment of trauma, stroke, myocardial infarction, and sepsis patients, improving early recognition, resuscitation, and transport. Emergency Medical Service personnel provide similar care for patients with syncope. The role of EMS in the management of patients with syncope has not been reported.
The objective of this study was to describe the management of out-of-hospital syncope by prehospital providers in an urban EMS system.
This was a retrospective cohort study of consecutively enrolled patients over 18 years of age, over a two-year period, who presented by EMS with syncope, or near-syncope, to a tertiary care emergency department (ED). Demographics included comorbidities, history, and physical exam findings documented by prehospital providers, as well as the interventions provided. Data were collected from standardized patient care records for descriptive analysis.
Of the 723 patients presenting with syncope to the ED, 284 (39.3%) were transported by EMS. Compared to non-EMS patients, those who arrived by ambulance were older (mean age 65 [SD = 18.5] years versus 61 [SD = 19.2] years; P = .019). There were no statistically significant differences in cardiovascular comorbidities (hypertension, coronary artery disease, diabetes mellitus, stroke, or congestive heart failure) between EMS and non-EMS patients. The most common chief complaints were fainting (50.0%) and dizziness (44.7%). The most common intervention provided was cardiac monitoring (55.6%), followed by administration of normal saline infusion (50.5%), oxygen (41.9%), blood glucose check (41.5%), and electrocardiogram (EKG; 40.5%).
Emergency Medical Service personnel transport more than one-third of patients presenting to the ED with syncope. Documentation of key elements of the history (witnesses, prodrome, predisposing factors, and post-event symptoms) and physical examination were not recorded consistently.
LongBJ, SerranoLA, CabanasJG, BellolioMF. Opportunities for Emergency Medical Services (EMS) Care of Syncope. Prehosp Disaster Med. 2016;31(4):349–352.
We have optically identified a complete sub-sample of ROSAT All-Sky Survey (RASS) X-ray sources contained in 6 study areas. Of the original 12° × 12° area near the NEP, only one-quarter was observed until now in order to keep the number of sources to a manageable size. This area is of particular interest because the RASS integration time is about a factor of ten longer than in the other areas and therefore a factor of 3-4 deeper in flux. We have started to observe the RASS sources in the remaining 3/4 of this area. First results are presented.
The potential of AGN surveys extends to structure-related objectives: e.g. to study the size and properties of the NLR in AGN. From a complete sample of 1665 radio sources, we selected fifty-five with features on ~0.2-2 kpc scales (core/jet flux ratio <7:1) for further study. Here, we summarize the radio interferometric selection technique used and speculate on the prospects for optical surveys (using a size criterion).