3,044 research outputs found

    Rapid detection, cloning and molecular cytogenetic characterisation of sequences from an MRP-encoding amplicon by chromosome microdissection.

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    Chromosome microdissection was utilised for the analysis of cytogenetic markers of gene amplification [homogeneously staining regions (hsrs) and double minutes (dmins)] in two doxorubicin-resistant cell lines, fibrosarcoma HT1080/DR4 and small-cell lung cancer H69AR. Microdissection products from the hsr(7)(p12p15) of HT1080/DR4 were amplified and used for fluorescent in situ hybridisation (micro-FISH) analysis of drug-sensitive HT1080, resistant HT1080/DR4 and normal lymphocytes. The results demonstrated that the hsr contains a domain of DNA amplification of complex origin including sequences derived from 16p11.2-16p13.1, 2q11.2, 7q32-7q34 and 10q22. The amplification was confirmed by converting the micro-dissected probe into a microclone library for probing HT1080 and HT1080/DR4 Southerns. A micro-FISH probe from normal band region 16p11-16p13 further demonstrated amplification of 16p sequences in both HT1080/DR4 and H69AR. During the course of this analysis, Cole et al. (1992) (Science, 258, 1650-1653) published the amplification of the MRP gene in H69AR cells, which maps to chromosome 16p13.1. Our results corroborate the finding of MRP amplification in these doxorubicin-resistant cell lines, but, importantly, they provide information on the composition of the complex amplicon contributions from four different chromosomes. This study demonstrates the potential utility of chromosome microdissection for the rapid recovery of sequences from amplified regions in drug-resistant cells

    Seismic imaging of the Northern Andean subduction zone from teleseismic tomography: a torn and fragmented Nazca slab

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    The Nazca-South America subduction zone in Ecuador is characterized by a complicated along-strike geometry as the slab transitions from flat slab subduction in the south, with the Peruvian flat slab, to what has been characterized as ‘normal’ dipping subduction beneath central Ecuador. Plate convergence additionally changes south to north as the trench takes on a convex shape. Highly heterogeneous bathymetry at the trench, including the aseismic oceanic Carnegie Ridge (CR), and sparse intermediate-depth seismicity has led many to speculate about the behaviour of the downgoing plate at depth. In this study, we present a finite-frequency teleseismic P-wave tomography model of the northern Andes beneath Ecuador and Colombia from 90 to 1200 km depth. Our model builds on prior tomography models in South America by adding relative traveltime residuals recorded at stations in Ecuador. The complete data set is comprised of 114 096 relative traveltime residuals from 1133 stations across South America, with the added data serving to refine the morphology of the Nazca slab in the mantle beneath the northern Andes. Our tomography model shows a Nazca slab with a fragmented along-strike geometry and the first teleseismic images of several proposed slab tears in this region. At the northern edge of the Peruvian flat slab in southern Ecuador, we image a shallow tear at 95–200 km depth that appears to connect mantle flow from beneath the flat slab to the Ecuadorian Arc. Beneath central Ecuador at the latitudes of the CR, the Nazca slab is continuous into the lower mantle. Beneath southern Colombia, the Malpelo Tear breaks the Nazca slab below ∼200 km depth

    Fexofenadine is Efficacious and Safe in Children (Aged 6-11 Years) with Seasonal Allergic Rhinitis

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    Background: This is the first prospective, randomized, doubleblind, placebo-controlled study showing statistical improvement of an H1-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. Objective: This randomized, placebo-controlled, parallelgroup,double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. Methods: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (±1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point

    Is primary care ready to take on Attention Deficit Hyperactivity Disorder?

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    BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder. The management of ADHD has recently been highlighted. The National Institute of Clinical Excellence (NICE) and Scottish Intercollegiate Guidelines network (SIGN) have both produced management guidelines. Doctors working within Primary Care in countries such as the United States play an important role in the management of ADHD. In the United Kingdom however the role of doctors in primary care in the management of ADHD, both individually and within shared care protocols, is only now being identified and defined. Is this role for Primary Care likely to be acceptable and effective? DISCUSSION: There is some evidence that doctors working within Primary Care in the United Kingdom are willing to follow up children on medication for ADHD and carry out monitoring of physical status. However many feel unconfident in the management of ADHD and most have received little or no training in child psychiatry. There are also concerns that adverse media reports will have an undue influence on the attitudes of doctors within primary care to families with children suffering from ADHD. SUMMARY: There are important barriers to be tackled before shared care protocols for ADHD can be successfully implemented in the United Kingdom. Tailored information about ADHD needs to be provided to doctors in primary care. Clear dialogue between planners and healthcare professionals from both primary and secondary care is essential to ensure that service delivery is acceptable to healthcare providers, tailored to their skills and is adequately resourced

    Development and validation of instruments measuring body image and body weight dissatisfaction in South African mothers and their daughters

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    Objective We sought to validate questionnaires concerning body image perception, body size dissatisfaction and weight-related beliefs in multi-ethnic South African mothers and their daughters. Settings and subjects: Girls attending primary school (ages 9-12 years, n = 333) and their mothers (n = 204) were interviewed regarding their demographics and body image. Weight, height and skinfold thicknesses were measured. Body image questions and body mass index (BMI) were compared with silhouettes adapted from the Pathways Study for girls and Stunkard\u27s body image figures for mothers. A Feel-Ideal Difference (FID) index score was created by subtracting the score of the silhouette selected by the participants as \u27Ideal\u27 from the one selected as most closely representing their current appearance or \u27Feel\u27. We hypothesised that a higher FID index score would be associated with greater body size dissatisfaction. Results BMI percentiles in girls (r = 0.46, P \u3c 0.05) and BMI in mothers (r = 0.68, P \u3c 0.05) were positively correlated with the selected silhouettes based on size. Participants who reported feelings of being \u27fat\u27 and those who perceived that their family and friends were more dissatisfied with their body size had significantly higher FID index scores. Scores were lower in black than white girls (all P \u3c 0.05). No differences were found in FID index scores between ethnic groups of mothers. Internal reliability of the \u27thin\u27 and \u27fat\u27 belief constructs for girls was demonstrated by standardised Cronbach\u27s α values ≥ 0.7. Conclusion Silhouettes, FID index, \u27fat\u27 and \u27thin\u27 belief constructs (in girls) are age-appropriate, culturally sensitive and can be used in further intervention studies to understand body image

    Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

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    Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

    Molecular-orbital theory for the stopping power of atoms in the low velocity regime:the case of helium in alkali metals

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    A free-parameter linear-combination-of-atomic-orbitals approach is presented for analyzing the stopping power of slow ions moving in a metal. The method is applied to the case of He moving in alkali metals. Mean stopping powers for He present a good agreement with local-density-approximation calculations. Our results show important variations in the stopping power of channeled atoms with respect to their mean values.Comment: LATEX, 3 PostScript Figures attached. Total size 0.54

    Anisotropic dark energy stars

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    A model of compact object coupled to inhomogeneous anisotropic dark energy is studied. It is assumed a variable dark energy that suffers a phase transition at a critical density. The anisotropic Lambda-Tolman-Oppenheimer-Volkoff equations are integrated to know the structure of these objects. The anisotropy is concentrated on a thin shell where the phase transition takes place, while the rest of the star remains isotropic. The family of solutions obtained depends on the coupling parameter between the dark energy and the fermion matter. The solutions share several features in common with the gravastar model. There is a critical coupling parameter that gives non-singular black hole solutions. The mass-radius relations are studied as well as the internal structure of the compact objects. The hydrodynamic stability of the models is analyzed using a standard test from the mass-radius relation. For each permissible value of the coupling parameter there is a maximum mass, so the existence of black holes is unavoidable within this model.Comment: 12 pages, 6 figures, final manuscript, Accepted for publication in Astrophysics & Space Scienc
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