This investigation adapts and extends the Social Cognitive Career Theory (SCCT) by integrating it with central constructs from turnover theory. The extended model proposes that domain specific ...self-efficacy and outcome expectations predict job satisfaction and organizational commitment — the two key job attitudes that have been established as influential predictors of turnover cognitions and behaviors. Further, we proposed that one form of organizational supports, specifically developmental opportunities at work, are sources of self efficacy and outcome expectations, and that the relationship between organizational supports and job attitudes is mediated by self-efficacy and outcome expectations. The proposed model was tested on a national sample of 2,042 women engineers. Overall, the results provided support for our newly developed model. Implications for theory, research, and practice are discussed.
•Extended Social Cognitive Career Theory to include organizational exit decisions•Extended affect driven turnover models to include agentic and motivational drivers•Results show self-efficacy and outcome expectations are positively related to job attitudes.•Job attitudes (job satisfaction and organizational commitment) are negatively related to turnover intentions.•Organizational supports directly influence self-efficacy and outcome expectations and indirectly job attitudes.
The proteasome was validated as an oncology target following the clinical success of VELCADE (bortezomib) for injection for the treatment of multiple myeloma and recurring mantle cell lymphoma. ...Consequently, several groups are pursuing the development of additional small-molecule proteasome inhibitors for both hematologic and solid tumor indications. Here, we describe MLN9708, a selective, orally bioavailable, second-generation proteasome inhibitor that is in phase I clinical development. MLN9708 has a shorter proteasome dissociation half-life and improved pharmacokinetics, pharmacodynamics, and antitumor activity compared with bortezomib. MLN9708 has a larger blood volume distribution at steady state, and analysis of 20S proteasome inhibition and markers of the unfolded protein response confirmed that MLN9708 has greater pharmacodynamic effects in tissues than bortezomib. MLN9708 showed activity in both solid tumor and hematologic preclinical xenograft models, and we found a correlation between greater pharmacodynamic responses and improved antitumor activity. Moreover, antitumor activity was shown via multiple dosing routes, including oral gavage. Taken together, these data support the clinical development of MLN9708 for both hematologic and solid tumor indications.
Past studies typically have focused on whether people perceive more rare risk after experiencing catastrophic disasters. We show that people can also feel less risk with unexpected lucky disaster ...experience. By exploring a novel identification strategy based on households’ expectations, we find that households perceive less (more) risk when they experience disasters that have lower (higher) fatalities than what was expected. This opposite experience effect of rare disasters is substantial. A one standard deviation increase in the negative (positive) experience shock is associated with a 1.71% decrease (a 1.31% increase) in the life insurance-to-portfolio ratio. We discuss three possible mechanisms to account for our empirical findings: incomplete information learning, salience theory, and change in risk preferences.
Background
Racial disparities among clinical trial participants present a challenge to assess whether trial results can be generalized into patients representing diverse races and ethnicities. The ...objective of this study was to evaluate the impact of race and ethnicity on treatment response in patients with advanced non‐small cell lung cancer (aNSCLC) treated with programmed cell death‐1 (PD‐1) or programmed cell death‐ligand 1 (PD‐L1) inhibitors through analysis of real‐world data (RWD).
Materials and Methods
A retrospective cohort study of 11,138 patients with lung cancer treated at hospitals within the Mount Sinai Health System was performed. Patients with confirmed aNSCLC who received anti‐PD‐1/PD‐L1 treatment were analyzed for clinical outcomes. Our cohort included 249 patients with aNSCLC who began nivolumab, pembrolizumab, or atezolizumab treatment between November 2014 and December 2018. Time‐to‐treatment discontinuation (TTD) and overall survival (OS) were the analyzed clinical endpoints.
Results
After a median follow‐up of 14.8 months, median TTD was 7.8 months (95% confidence interval, 5.4–not estimable NE) in 75 African American patients versus 4.6 (2.4–7.2) in 110 White patients (hazard ratio HR, 0.63). Median OS was not reached (18.4–NE) in African American patients versus 11.6 months (9.7–NE) in White patients (HR, 0.58). Multivariable Cox regression conducted with potential confounders confirmed longer TTD (adjusted HR, 0.65) and OS (adjusted HR, 0.60) in African American versus White patients. Similar real‐world response rate (42.6% vs. 43.5%) and disease control rate (59.6% vs. 56.5%) were observed in the African American and White patient populations. Further investigation revealed the African American patient group had lower incidence (14.7%) of putative hyperprogressive diseases (HPD) upon anti‐PD‐1/PD‐L1 treatment than the White patient group (24.5%).
Conclusion
Analysis of RWD showed longer TTD and OS in African American patients with aNSCLC treated with anti‐PD‐1/PD‐L1 inhibitors. Lower incidence of putative HPD is a possible reason for the favorable outcomes in this patient population.
Implications for Practice
There is a significant underrepresentation of minority patients in randomized clinical trials, and this study demonstrates that real‐world data can be used to investigate the impact of race and ethnicity on treatment response. In retrospective analysis of patients with advanced non‐small cell lung cancer treated with programmed cell death‐1 or programmed cell death‐ligand 1 inhibitors, African American patients had significantly longer time‐to‐treatment discontinuation and longer overall survival. Analysis of real‐world data can yield clinical insights and establish a more complete picture of medical interventions in routine clinical practice.
Racial disparities in clinical trials affect whether trial results can be generalized for diverse patient populations. This article evaluates real‐world data to assess the impact of race and ethnicity on treatment response in patients with advanced non‐small cell lung cancer treated with PD‐1 or PD‐L1 inhibitors.
Direct cloning and parallel sequencing, an extremely powerful method for microRNA (miRNA) discovery, has not yet been applied to bacterial transcriptomes. Here we present sRNA-Seq, an unbiased method ...that allows for interrogation of the entire small, non-coding RNA (sRNA) repertoire in any prokaryotic or eukaryotic organism. This method includes a novel treatment that depletes total RNA fractions of highly abundant tRNAs and small subunit rRNA, thereby enriching the starting pool for sRNA transcripts with novel functionality. As a proof-of-principle, we applied sRNA-Seq to the human pathogen Vibrio cholerae. Our results provide information, at unprecedented depth, on the complexity of the sRNA component of a bacterial transcriptome. From 407 039 sequence reads, all 20 known V. cholerae sRNAs, 500 new, putative intergenic sRNAs and 127 putative antisense sRNAs were identified in a limited number of growth conditions examined. In addition, characterization of a subset of the newly identified transcripts led to the identification of a novel sRNA regulator of carbon metabolism. Collectively, these results strongly suggest that the number of sRNAs in bacteria has been greatly underestimated and that future efforts to analyze bacterial transcriptomes will benefit from direct cloning and parallel sequencing experiments aided by 5S/tRNA depletion.
Carbon and water fluxes in ecosystems are tightly coupled by gas diffusion through stomata. However, carbon–water (C–W) relationships vary largely across time scales, vegetation types, and regions. ...Subtropical forests in China play an important role in the global carbon and water cycles, yet studies of C–W relationships in this region remain limited. Here, we investigated summer-time C–W relationships in this region at two subtropical sites: the evergreen broadleaved forest at Dinghushan (23.17° N, 112.53° E, 300 m) and the evergreen coniferous forest at Qianyanzhou (26.74° N, 115.06° W, 106 m), using the flux tower data from the FLUXNET2015. The C–W relationship was examined using two measures. The first was daily water use efficiency (WUE), which is the ratio of daily gross primary productivity (GPP) to evapotranspiration (ET). The second was the correlation coefficient (r) of hourly GPP and ET. Our analysis showed that the daily WUE in the two forests ranged over 4–14 mg CO2 per g H2O, higher in the coniferous forest than in the broadleaved forest. The mean values of r for hourly C–W coupling were similar at the two forests, being 0.5–0.6, which suggests asynchronous diurnal variations in GPP and ET. Both daily WUE and r were modulated by meteorological conditions. In general, high radiation, air temperature, and humidity can reduce WUE at both sites. For the broadleaved forest, the most influential factor on WUE was VPD, followed by radiation, while in the coniferous forest, VPD, air temperature, and radiation were almost equally important. For hourly C–W coupling, VPD plays a significant role. The drier the air is, the weaker the coupling in the two forests. The daily WUE and hourly C–W coupling reflect the C–W relationship from different perspectives. Both showed the strongest response to VPD but with different sensitivity.
We evaluate the potential of using a process-based ecosystem model (BEPS) for crop biomass mapping at 20 m resolution over the research site in Manitoba, western Canada driven by spatially explicit ...leaf area index (LAI) retrieved from Sentinel-2 spectral reflectance throughout the entire growing season. We find that overall, the BEPS-simulated crop gross primary production (GPP), net primary production (NPP), and LAI time-series can explain 82%, 83%, and 85%, respectively, of the variation in the above-ground biomass (AGB) for six selected annual crops, while an application of individual crop LAI explains only 50% of the variation in AGB. The linear relationships between the AGB and these three indicators (GPP, NPP and LAI time-series) are rather high for the six crops, while the slopes of the regression models vary for individual crop type, indicating the need for calibration of key photosynthetic parameters and carbon allocation coefficients. This study demonstrates that accumulated GPP and NPP derived from an ecosystem model, driven by Sentinel-2 LAI data and abiotic data, can be effectively used for crop AGB mapping; the temporal information from LAI is also effective in AGB mapping for some crop types.
Continuous increases in the human population and human activities have resulted in remarkable changes in the composition of the atmosphere since the industrial revolution ...
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