59 research outputs found
Anomalous magneto-transport at the superconducting interface between LaAlO3 and SrTiO3
The magnetoresistance as a function of temperature and field for atomically
flat interfaces between 8 unit cells of LaAlO3 and SrTiO3 is reported.
Anomalous anisotropic behavior of the magnetoresistance is observed below 30 K
for superconducting samples with carrier concentration of 3.5\times10^13 cm^-2
. We associate this behavior to a magnetic order formed at the interface.Comment: 2 pages, 3 figures. Proceedings of the 9th International Conference
on Materials and Mechanisms of Superconductivit
Community professionals' management of client care : a mixed-methods systematic review
This is the final draft, after peer-review, of a manuscript published in Journal of Health Services Research & Policy. The definitive version, detailed above, is available online at www.rsmjournals.com.Peer reviewedPostprin
Service usersâ first accounts of experiencing endings from a psychological service or therapy: a systematic review and meta-ethnographic synthesis
Purpose: To review and synthesis the qualitative literature on service usersâ experiences of endings from a psychological service or therapy. Methods: A systematic search of the peer-reviewed literature was conducted. Studies were identified using specific inclusion criteria and included in the synthesis. A modified CASP tool was used to critically appraise the quality of the papers. A meta-ethnographic approach was used to synthesize the findings from the included studies. Results: Twelve papers were identified which met the inclusion criteria. The interpretation of findings suggested three key themes: anticipation of ending, service user control and sense of responsibility. Studies were geographically spread and of high quality. Conclusions: The review highlights the importance of service usersâ perspectives in understanding the experiences of endings. The findings complement existing literature and provide new interpretations. Considerations for practice in the UK were limited however the review does provide directions for future research
Working with the complexities of adolescent mental health problems: applying time-limited adolescent psychodynamic psychotherapy (TAPP)
Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae
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Exome and whole genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity
The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a mutational signature defined by a high prevalence of A to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis
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The genetic landscape of high-risk neuroblastoma
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers
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Mutational heterogeneity in cancer and the search for new cancer genes
Major international projects are now underway aimed at creating a comprehensive catalog of all genes responsible for the initiation and progression of cancer. These studies involve sequencing of matched tumorânormal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here, we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false positive findings that overshadow true driver events. Here, we show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumor-normal pairs and discover extraordinary variation in (i) mutation frequency and spectrum within cancer types, which shed light on mutational processes and disease etiology, and (ii) mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and allow true cancer genes to rise to attention
Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations
Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2â5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma
Novel MRGPRX2 antagonists inhibit IgEâindependent activation of human umbilical cord bloodâderived mast cells
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