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"Gamble, Adam"
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Good night America
Easy-to-read text introduces the sights of America through a full day of sightseeing.
Book
Correction: Protocol for research examination of individual suicides occurring in chronic pain: A qualitative approach to psychological autopsy methodology
[This corrects the article DOI: 10.1371/journal.pone.0329874.].
Journal Article
Good night, farm
Easy-to-read text enumerates the sights and chores of a farm throughout the days and across the seasons.
Book
Whole exome sequencing of adenoid cystic carcinoma
Adenoid cystic carcinoma (ACC) is a rare malignancy that can occur in multiple organ sites and is primarily found in the salivary gland. While the identification of recurrent fusions of the MYB-NFIB genes have begun to shed light on the molecular underpinnings, little else is known about the molecular genetics of this frequently fatal cancer. We have undertaken exome sequencing in a series of 24 ACC to further delineate the genetics of the disease. We identified multiple mutated genes that, combined, implicate chromatin deregulation in half of cases. Further, mutations were identified in known cancer genes, including PIK3CA, ATM, CDKN2A, SF3B1, SUFU, TSC1, and CYLD. Mutations in NOTCH1/2 were identified in 3 cases, and we identify the negative NOTCH signaling regulator, SPEN, as a new cancer gene in ACC with mutations in 5 cases. Finally, the identification of 3 likely activating mutations in the tyrosine kinase receptor FGFR2, analogous to those reported in ovarian and endometrial carcinoma, point to potential therapeutic avenues for a subset of cases.
Journal Article
Count to sleep Yosemite
Learn to count and see the sights of Yosemite National Park at the same time.
Book
RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia
Peter Campbell, Mel Greaves and colleagues use exome and whole-genome sequencing to characterize somatic mutations in childhood acute lymphoblastic leukemias with the
ETV6
-
RUNX1
fusion gene. They find that RAG-mediated deletions are the dominant mutational process.
The
ETV6
-
RUNX1
fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL) cases, is acquired
in utero
but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, characterized by recombination signal sequence motifs near breakpoints, incorporation of non-templated sequence at junctions, ∼30-fold enrichment at promoters and enhancers of genes actively transcribed in B cell development and an unexpectedly high ratio of recurrent to non-recurrent structural variants. Single-cell tracking shows that this mechanism is active throughout leukemic evolution, with evidence of localized clustering and reiterated deletions. Integration of data on point mutations and rearrangements identifies
ATF7IP
and
MGA
as two new tumor-suppressor genes in ALL. Thus, a remarkably parsimonious mutational process transforms
ETV6
-
RUNX1
–positive lymphoblasts, targeting the promoters, enhancers and first exons of genes that normally regulate B cell differentiation.
Journal Article
Good night families
Diverse families enjoy spending a day together engaging in such activities as playing at the park, biking, reading, and going to the beach.
Book
Protocol for research examination of individual suicides occurring in chronic pain: A qualitative approach to psychological autopsy methodology
In the United States, taper and discontinuation of opioids prescribed for long-term pain have emerged as statistical correlates of suicidal events. Suicide is a complex and multidetermined event reflecting a combination of risks occurring over time in a particular narrative context. Prevention of suicides should be informed by a detailed understanding of life events, pain-related and other risk factors contributing to these tragedies. To date, there have been no efforts to qualitatively profile these suicides through interview of bereaved survivors or review of medical records. This method is usually termed \"psychological autopsy.\".
This paper summarizes the protocol for the Clinical Context of Suicide Following Opioid Transitions (CSI:OPIOIDs) study. The study seeks to qualitatively characterize patient and clinical context factors associated with suicide among persons who died by suicide in the context of opioid stoppage or reduction, and to compare findings between Veteran and non-Veteran decedents.
In the United States, there is no master list for suicide deaths linked to an antemortem health care event. For this reason, recruitment requires public advertising followed by screening of bereaved individuals who wish to participate. Data collection and interpretation are guided by the Social-Ecological Model for suicide. The study involves a collaboration of persons with lived experience and disciplinary experts in suicide, primary care, pain, health services, and medical anthropology.
This study aims to deliver the first in-depth analysis of suicide events occurring in persons with chronic pain who died by suicide in the context of a prescription opioid reduction or stoppage. The results should provide insights that can guide alterations to care by health systems and by individual practitioners.
Journal Article