Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.
There is a clear need and desire to develop policy based on evidence of what works. However, evidence on what works in terms of disrupting drugs supply remains unclear. In this article a ‘systematic’ review of the research evidence that focuses on attempts to disrupt local retail drug markets is undertaken. The search was conducted for studies in English using electronic databases, citation indexes and journal abstracts. Papers were reviewed for five methodological criteria which 15 studies met. These 15 studies fell into two distinct groups: evaluations of interventions to disrupt drug-dealing from residential or commercial properties; and interventions which sought to disrupt drug dealing taking place in the open or on city streets. Studies were then graded according to the effectiveness of the invention they evaluated. Finally, areas of effectiveness along with implications for designing interventions and evaluations are discussed.
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