Open Access to Large Scale Datasets Is Needed to Translate Knowledge of Cancer Heterogeneity into Better Patient Outcomes

In this guest editorial, Andrew Beck discusses the importance of open access to big data for translating knowledge of cancer heterogeneity into better outcomes for cancer patients

Lawyer Distress: Alcohol-Related Problems and Other Psychological Concerns Among a Sample of Practicing Lawyers

Suspending an attorney\u27s license for sixty days for neglecting client matters, making misrepresentations to the district court, and failing to timely respond to the disciplinary board; his depression was a mitigating factor in imposing discipline

Lawyer Distress: Alcohol-Related Problems and Other Psychological Concerns among a Sample of Practicing Lawyers

The findings of the research reported in this study, in conjunction with earlier studies, suggest that the professional and the personal well-being of lawyers is in serious jeopardy. Lawyers are working more, reducing vacation time, spending less time with family members, are prone to alcohol abuse, and face high levels of psychological distress. The combination of elements suggests an impending crisis for lawyers\u27 family lives. Although the data are not sufficient to suggest that psychological distress has detrimentally affected the lawyers\u27 ability to practice competently, the warning signs are present. Further empirical study may well reveal that lawyer distress is having an adverse effect on the ability to practice competently and ethically

Lawyer Distress: Alcohol-Related Problems and Other Psychological Concerns Among a Sample of Practicing Lawyers

Holding that an attorney suffering from depression was suspended from the practice of law for a period of 120 days; suspension was to ensure there would be evidence of a meaningful and sustained recovery before the attorney was allowed to return to practice.

Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma

Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132's strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS

Importance of collection in gene set enrichment analysis of drug response in cancer cell lines

Gene set enrichment analysis (GSEA) associates gene sets and phenotypes, its use is predicated on the choice of a pre-defined collection of sets. The defacto standard implementation of GSEA provides seven collections yet there are no guidelines for the choice of collections and the impact of such choice, if any, is unknown. Here we compare each of the standard gene set collections in the context of a large dataset of drug response in human cancer cell lines. We define and test a new collection based on gene co-expression in cancer cell lines to compare the performance of the standard collections to an externally derived cell line based collection. The results show that GSEA findings vary significantly depending on the collection chosen for analysis. Henceforth, collections should be carefully selected and reported in studies that leverage GSEA

High-Latitude Tree Growth and Satellite Vegetation Indices: Correlations and Trends in Russia and Canada (1982-2008)

Vegetation in northern high latitudes affects regional and global climate through energy partitioning and carbon storage. Spaceborne observations of vegetation, largely based on the normalized difference vegetation index (NDVI), suggest decreased productivity during recent decades in many regions of the Eurasian and North American boreal forests. To improve interpretation of NDVI trends over forest regions, we examined the relationship between NDVI from the advanced very high resolution radiometers and tree ring width measurements, a proxy of tree productivity. We collected tree core samples from spruce, pine, and larch at 22 sites in northeast Russia and northwest Canada. Annual growth rings were measured and used to generate site-level ring width index (RWI) chronologies. Correlation analysis was used to assess the association between RWI and summer NDVI from 1982 to 2008, while linear regression was used to examine trends in both measurements. The correlation between NDVI and RWI was highly variable across sites, though consistently positive (r = 0.43, SD = 0.19, n = 27). We observed significant temporal autocorrelation in both NDVI and RWI measurements at sites with evergreen conifers (spruce and pine), though weak autocorrelation at sites with deciduous conifers (larch). No sites exhibited a positive trend in both NDVI and RWI, although five sites showed negative trends in both measurements. While there are technological and physiological limitations to this approach, these findings demonstrate a positive association between NDVI and tree ring measurements, as well as the importance of considering lagged effects when modeling vegetation productivity using satellite data