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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
Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, and modulate the host immune system, which may aid worm infection establishment, maintenance and survival in the host. Here we have identified and characterized a σ class glycosylated GST (OoGST1), from the cattle-infective filarial nematode Onchocerca ochengi, which is homologous (99% amino acid identity) with an immunodominant GST and potential vaccine candidate from the human parasite, O. volvulus, (OvGST1b). Onchocerca ochengi native GSTs were purified using a two-step affinity chromatography approach, resolved by 2D and 1D SDS-PAGE and subjected to enzymic deglycosylation revealing the existence of at least four glycoforms. A combination of lectin-blotting and mass spectrometry (MS) analyses of the released N-glycans indicated that OoGST1 contained mainly oligomannose Man5GlcNAc2 structure, but also hybrid- and larger oligommanose-type glycans in a lower proportion. Furthermore, purified OoGST1 showed prostaglandin synthase activity as confirmed by Liquid Chromatography (LC)/MS following a coupled-enzyme assay. This is only the second reported and characterized glycosylated GST and our study highlights its potential role in host-parasite interactions and use in the study of human onchocerciasis.
The predominantly carbonate nature of the mountains near the coast of Málaga and Marbella (Costa del Sol, southern Spain) and the presence of springs have favored the formation of travertine buildups during the Quaternary. The geomorphic characteristics of the slopes and the location of the springs have determined the development of three types of travertine growths: (1) spring travertines, located preferentially on the south mountainside, where the slope is steepest; (2) pool-dam-cascade travertines, which form along the north and east edges, far from the carbonate relief and with a gentler slope; and (3) river-valley travertines, formed in the courses of the springs of any sector. Field observations combined with new amino acid racemization (AAR) dating of Helicidae gastropods show that most of the travertine formations are polyphasic and that their development was interrupted by stages of erosion and incision. Five stages of travertine development are evident, most of which are related to warm, moist episodes corresponding to marine oxygen isotope stages (MIS) 7, 5, 3, and 1, although local travertine growth also occurred during MIS 6 and during the transition from MIS 3 to 2.
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.
Williams syndrome (WS) is a neurodevelopmental disorder that results from a heterozygous microdeletion on chromosome 7q11.23. Most of the time, the affected region contains ~1.5 Mb of sequence encoding approximately 24 genes. Some 5–8% of patients with WS have a deletion exceeding 1.8 Mb, thereby affecting two additional genes, including GTF2IRD2. Currently, there is no consensus regarding the implications of GTF2IRD2 loss for the neuropsychological phenotype of WS patients. Objectives: The present study aimed to identify the role of GTF2IRD2 in the cognitive, behavioral, and adaptive profile of WS patients. Methods: Twelve patients diagnosed with WS participated, four with GTF2IRD2 deletion (atypical WS group), and eight without this deletion (typical WS group). The age range of both groups was 7–18 years old. Each patient’s 7q11.23 deletion scope was determined by chromosomal microarray analysis. Cognitive, behavioral, and adaptive abilities were assessed with a battery of neuropsychological tests. Results: Compared with the typical WS group, the atypical WS patients with GTF2IRD2 deletion had more impaired visuospatial abilities and more significant behavioral problems, mainly related to the construct of social cognition. Conclusions: These findings provide new evidence regarding the influence of the GTF2IRD2 gene on the severity of behavioral symptoms of WS related to social cognition and certain visuospatial abilities. (JINS, 2018, 24, 896–904)
TorsinA is a member of the AAA+ superfamily of adenosine triphosphatases. These AAA+ proteins have numerous biological functions, including vesicle fusion, cytoskeleton dynamics, intracellular trafficking, protein folding, and degradation as well as organelle biogenesis. Of particular interest is torsinA, which is mainly located in the endoplasmic reticulum (ER) and nuclear envelope (NE). Interestingly, mutations in the TOR1A gene (the gene encoding torsinA) are associated with DYT1 dystonia and with the preferential localization of mutated torsinA at the NE, where it is associated with lamina-associated polypeptide 1. A bioinformatics study of the torsinA interactome revealed reproductive processes to be highly relevant, as proteins in this class were found to interact with the former. Interestingly, the torsin protein family had never been previously described to be associated with the mammalian spermatogenic process. Histological staining of torsinA in human testis tissue revealed a granular cytoplasmic localization in mid- and late spermatocytes. We further sought to understand this newly discovered expression of torsinA in the meiotic phase of human spermatogenesis by studying its specific subcellular distribution. TorsinA is not present in the ER as commonly described. The proposal that torsinA might relocate to the pro-acrosomal vesicles in the Golgi apparatus is discussed.
Trimethoprim/sulfamethoxazole has been suggested as a treatment option for chronic rhinosinusitis with purulence. This study aimed to assess the functional and endoscopic outcomes after a three-month course of low-dose trimethoprim/sulfamethoxazole.
A prospective study was performed, comprising patients referred to a tertiary care medical centre with a diagnosis of chronic rhinosinusitis with purulence. Trimethoprim/sulfamethoxazole was prescribed at 960 mg/day for three months. Sinonasal complaints and endoscopic findings were documented, and bacteriological data were compared.
Fifteen patients were included. Staphylococcus aureus was the most common bacterium cultured (86 per cent). Improvement in nasal function, as measured by the 22-item Sino-Nasal Outcome Test, was highly significant at three months (p < 0.0005). This improvement slightly decreased but remained significant at 6, 9 and 12 months. No side effects were noted. Endoscopic scores revealed similar and concordant improvements.
Long-term low-dose trimethoprim/sulfamethoxazole therapy seems to be a safe option for selected patients. Additional randomised multicentre studies remain necessary.
We report here an observational study on the IR properties of members of the rich clusters of galaxies: Abell 194, Perseus and Hercules. Following the precepts described in previous papers concerning the manifold of the early-type galaxies from IR photometry for the Coma (Recillas-Cruz et al. 1990) and Virgo (Recillas-Cruz et al. 1991) cluster members; interstellar reddening and redshift corrections for Abell 194, Perseus and Hercules were estimated. Interstellar reddening corrections for Abell 194 and Hercules galaxy members were found to be small, except for Perseus cluster galaxies where extinction values are somewhat larger. IR redshift K-corrections were estimated from linear relations with z for (J-H), (H-K) and K (Persson et al. 1979). Corrected magnitudes and colors were then used to construct (J-H) vs. (H-K) diagrams for elliptical and S0 galaxies and color-magnitude diagrams (J-H), (H-K), (J-K), (B-K) and (V-K) vs. K.
We have analyzed luminosity profiles of E galaxies in six clusters of galaxies. We have found a relationship between radius, luminosity and surface brightness for galaxies in each of the clusters. Moreover, it seems that there is a dependence of the zero point of the relation with environment. This relationship implies that there is not a universal luminosity profile for elliptical galaxies.
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.
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.
Euclid is a Europe-led cosmology space mission dedicated to a visible and near infrared survey of the entire extra-galactic sky. Its purpose is to deepen our knowledge of the dark content of our Universe. After an overview of the Euclid mission and science, this contribution describes how the community is getting organized to face the data analysis challenges, both in software development and in operational data processing matters. It ends with a more specific account of some of the main contributions of the Swiss Science Data Center (SDC-CH).
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 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).
Many searches have been carried out to detect emission from massive primeval hydrogen clouds at high redshift. By observing the 21 cm line it has been possible to impose strong upper limits on the mass and number of protoclusters at high redshift (Wieringa, et al. 1992). Since strong Lyα emission is expected from primeval galaxies undergoing their first burst of star formation, many attempts to detect this emission have been made, but no positive detection has been reported, imposing strong constraints on models of galaxy formation (see Djorgovski et al. 1993 for a review).
Recent research has shown an association between unemployment and suicide, but the mediating factors in this relationship are still unknown. In this study, we investigated the effect of unemployment and economic recession on suicide rates in the Spanish region of Galicia between 1975 and 2012
We analysed age-standardised suicide rates in men and women and in four age groups: less than 25 years, 25–45 years, 45–65 years and more than 65 years and performed a joinpoint analysis to determine trend changes throughout 1975–2012 period. Also we analysed the association between suicide, recession and unemployment by means of a temporal trend model with a Generalised Additive Model.
Suicide rates increased from 145 suicides in 1975 to a high in 1993, with 377 deaths by suicide, representing 1.38% of all causes of death, and thereafter they tend to decrease to 335 suicides in 2012. Joinpoint analyses revealed that suicide rates changed differently across sex and age groups. For men, the annual percentage of change (APC) between 1975 and 1988 (CI 95% 1986–1994) was 5.45 (CI 95% = 3.5, −7.2) but from 1988 the APC became negative [−0.66 (CI 95% = −1.3, −0.1)]. For women, APC between 1974 and 1990 (CI 95% 1986–1992) was 4.86 (CI 95% = 3.2, −6.4) and −1.46 subsequently (CI 95% = −2.2, −0.5). Women aged 24 years or less showed stable suicide rates while men from 45–65 years showed two incidence peaks. When we studied the independent correlation between unemployment, recession and suicide, we found a significant association between unemployment and suicide, but not between recession and suicide for both sexes together and for men while for women there was no significant correlation between suicide and unemployment or recession. Finally, when we studied the effect of the interaction between unemployment and recession on suicide we found economic recession and unemployment interacted with regards to suicide rates (F = 5.902; df = 4.167; p = 0.00098) and after adjusting by sex, the effect was confirmed among men (F = 4.827; df = 2.823; p = 0.0087), but not among women (F = 0.001; df = 1.000; p = 0.979).
Although suicide rates in Galicia are gradually decreasing in the last decades, there are important sex and age differences. Unemployment was related with suicide during economic recession periods according to our results.
Surveys with ISO (Kessler et al 1996), in particular with the CAM (Cesarsky et al 1996) and PHOT (Lemke et al 1996) instruments, will greatly extend our understanding of extra-galactic populations and their cosmological evolution. The main advantages that ISO surveys have over e.g IRAS are increased sensitivity/depth and wavelength coverage. Within the Guaranteed and Open Time programmes there are many field surveys which will efficiently map the limits in these parameters. In this talk I will briefly overview those surveys before concentrating in more detail on one survey in particular, the ISO survey of the Hubble Deep Field (HDF), to illustrate the kind of results that can be expected.
This paper addresses the problem of trajectory tracking control in mobile robots under velocity limitations. Following the results reported in ref. , the problem of trajectory tracking considering control actions constraint is focused and the zero convergence of the tracking errors is demonstrated. In this work, the original methodology is expanded considering a controller that depends not only on the position but also on the velocity. A simple scheme is obtained, which can be easily implemented in others controllers of the literature. Experimental results are presented and discussed, demonstrating the good performance of the controller.
This paper aims to present the Integrated Atlas of Mental Health of Catalonia (2010) focusing on: (a) the importance of using a taxonomy-based coding and standard system of data collection when assessing health services; and (b) its relevance as a tool for evidence-informed policy.
This study maps all the care-related services for people with mental disorders available in Catalonia in 2010, using the ‘Description and Evaluation of Services and Directories in Europe for long-term care’ (DESDE-LTC). The unit of analysis is the Basic Stable Input of Care (BSIC), which is the minimal organisation unit composed by a set of inputs with temporal stability. We presented data on: (a) availability of BSICs and their capacity; (b) the adequacy of the provision of care, taking into account availability and accessibility; (c) the evolution of BSCIs from 2002 to 2010; and (d) the perceived relevance of Atlas of Mental Health as a tool for evidence-informed policy.
We identified a total of 639 BSICs. A lack of Health services was detected in highly rural areas, although there was moderate availability of Social Services. Overall, more than 80% of the small mental health areas in Catalonia had an adequate core mental health service. Since 2002 the availability of mental health services has increased. Decision makers found the Atlas a useful and relevant tool for evidence informed policy.
Policy makers can use Atlases to detect gaps and inequities in the provision of care for people with mental health needs.
Optical thresholds, that correspond to a level located at 1 eV above the valence band, are observed by photocapacitance techniques in n-type Mg-doped GaN. In undoped GaN, this level has been previously related to the yellow emission detected by photoluminescence. In Mg-doped GaN, this yellow luminescence is only observed for excitation energies below the Mg-related band (2.9 - 3 eV). This result evidences that Mg-doping may reduce but not avoid the formation of the yellow band related defects in n-type and semiinsulating Mg-doped samples. The fact that the yellow luminescence is not observed for excitation energies above the bandgap may be justified by a higher efficiency of the Mg-related recombination path.