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Small cell lung cancer patient outcomes have not yet been significantly impacted by the revolution in precision oncology, primarily due to a paucity of genetic alterations in actionable driver oncogenes. Nevertheless, systemic therapies that include immunotherapy are beginning to show promise in the clinic. While these results are encouraging, many patients do not respond to or rapidly recur after current regimens, necessitating alternative or complementary therapeutic strategies. In this review, we discuss ongoing investigations into the pathobiology of this recalcitrant cancer and the therapeutic vulnerabilities that are exposed by the disease state. Included within this discussion is a snapshot of the current biomarker and clinical trial landscapes for small cell lung cancer. Finally, we identify key knowledge gaps that should be addressed in order to advance the field in pursuit of reduced small cell lung cancer mortality. This review largely summarizes work presented at the Third Biennial IASLC Small Cell Lung Cancer Meeting.

This study uses employment data on California county-industry pairs (CIPs) between 1990 and 2016 to test whether minimum wage increases caused employment growth to slow most in the CIPS with a large share of low wage workers. Evidence supports the hypothesis, and we use the estimates to simulate the effect of a 10 percent increase in the minimum wage. The simulations suggest that a 10 percent increase could cause a 3.4 percent employment loss in the average CIP in California. The job loss is projected to be concentrated in two industries: accommodation and food services, and retail. While the most populated counties of California are expected to incur the largest employment loss in terms of the number of workers, the smaller counties generally experience a larger percentage point loss in employment due to the lower wages and the greater number of workers that would be affected by the minimum wage hike. Moreover, there is substantial variation across counties in terms of the percentage of jobs lost within a given industry.

Water pollution is a key environmental problem affecting modern day China. Increased human population, agricultural and advanced industrial activities present a complex multiple problems impacting water resource across China. This situation is more pronounced in Tianjing Lake, Tiacang City. Engineered in April 2012, the lake exemplifies severe eutrophication problems. Constructed for recreational uses, the lake plays a vital role in the economic and sociopolitical development of Tiacang City. As a result, the Tianjing Lake water transfer project was carried out in order to improve water quality and alleviate eutrophication. The project considered major field observations that monitored the lake’s nutrients concentrations (TN, TP, NH4, COD Mn) before and after water diversions. Results showed that the effects of water transfer on the overall water quality improvement in the lake seemed heterogeneous. The observed heterogeneity is as a result of the lake’s hydrodynamic conditions influenced by inflow tributaries. However, poor water movement resulting from the lack of outlet to actively expel pollutants may be a key factor compounding the lake’s internal nutrients management. This, however, dictates the engineering of additional flow directions in order to ensure better exchanges and additional nutrients removal through the expulsion via the outlet to improve water quality and sustain ecosystem health. Hence, this study provides useful information necessary to better understand the complex hydrodynamic and mass transport processes in the Tianjing Lake and present a road-map for future management decision-making.

Several murine retinoblastoma models have been generated by deleting the genes encoding for retinoblastoma susceptibility protein pRb and one of its family members p107 or p130. In Rb−/−p107−/− retinoblastomas, somatic copy number alterations (SCNAs) like Mdm2 amplification or Cdkn2a deletion targeting the p53-pathway occur, which is uncommon for human retinoblastoma. In our study, we determined SCNAs in retinoblastomas developing in Rb−/−p130−/− mice and compared this to murine Rb−/−p107−/− tumors and human tumors. Chimeric mice were made by injection of 129/Ola-derived Rb−/−p130−/− embryonic stem cells into wild type C57BL/6 blastocysts. SCNAs of retinoblastoma samples were determined by low-coverage (∼0.5×) whole genome sequencing. In Rb−/−p130−/− tumors, SCNAs included gain of chromosomes 1 (3/23 tumors), 8 (1/23 tumors), 10 (1/23 tumors), 11 (2/23 tumors), and 12 (4/23 tumors), which could be mapped to frequently altered chromosomes in human retinoblastomas. While the altered chromosomes in Rb−/−p130−/− tumors were similar to those in Rb−/−p107−/− tumors, the alteration frequencies were much lower in Rb−/−p130−/− tumors. Most of the Rb−/−p130−/− tumors (16/23 tumors, 70%) were devoid of SCNAs, in strong contrast to Rb−/−p107−/− tumors, which were never (0/15 tumors) SCNA-devoid. Similarly, to human retinoblastoma, increased age at diagnosis significantly correlated with increased SCNA frequencies. Additionally, focal loss of Cdh11 was observed in one Rb−/−p130−/− tumor, which enforces studies in human retinoblastoma that identified CDH11 as a retinoblastoma suppressor. Moreover, based on a comparison of genes altered in human and murine retinoblastoma, we suggest exploring the role of HMGA1 and SRSF3 in retinoblastoma development.