FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade

Prospectus, February 16, 2005

https://spark.parkland.edu/prospectus_2005/1004/thumbnail.jp

Oculomotor interference during manual response preparation: evidence from the response-cueing paradigm

Preparation provided by visual location cues is known to speed up behavior. However, the role of concurrent saccades in response to visual cues remains unclear. In this study, participants performed a spatial precueing task by pressing one of four response keys with one of four fingers (two of each hand) while eye movements were monitored. Prior to the stimulus, we presented a neutral cue (baseline), a hand cue (corresponding to left vs. right positions), or a finger cue (corresponding to inner vs. outer positions). Participants either remained fixated on a central fixation point or moved their eyes freely. The results demonstrated that saccades during the cueing interval altered the pattern of cueing effects. Finger cueing trials in which saccades were spatially incompatible (vs. compatible) with the subsequently required manual response exhibited slower manual RTs. We propose that interference between saccades and manual responses affects manual motor preparation

Prospectus, March 16, 2005

https://spark.parkland.edu/prospectus_2005/1008/thumbnail.jp

Policy evaluation via a statistical control: A non-parametric evaluation of the 'Want2Work' active labour market policy

Active labour market policies are popular tools used by governments to help get unemployed people back into work. It is a common problem that interventions of this type are often established with no equivalent control group on which to base an evaluation of programme effectiveness. This study uses propensity score matching to evaluate the success of an active labour market policy (the Welsh Assembly's 'Want2Work' programme) that cannot otherwise be evaluated using standard parametric techniques. Using a range of matching and estimation methods, sub-samples and types of job, the scheme was successful. Our most conservative estimate indicates that participants were 7 percentage points more likely to find employment than a control group of non-treated job-seekers. The method adopted here is a useful addition to the real world policy evaluation tool kit, where programme effectiveness needs to be judged in the absence of an established control group. Our results provide evidence that even those who are currently out of the labour market and on health related benefits can find work with the help of appropriately designed support

Mortality and Cardiovascular Disease among Older Live Kidney Donors

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation

Stability of zero-growth economics analysed with a Minskyan model

As humanity is becoming increasingly confronted by Earth's finite biophysical limits, there is increasing interest in questions about the stability and equitability of a zero-growth capitalist economy, most notably: if one maintains a positive interest rate for loans, can a zero-growth economy be stable? This question has been explored on a few different macroeconomic models, and both ‘yes' and ‘no’ answers have been obtained. However, economies can become unstable whether or not there is ongoing underlying growth in productivity with which to sustain growth in output. Here we attempt, for the first time, to assess via a model the relative stability of growth versus no-growth scenarios. The model employed draws from Keen's model of the Minsky financial instability hypothesis. The analysis focuses on dynamics as opposed to equilibrium, and scenarios of growth and no-growth of output (GDP) are obtained by tweaking a productivity growth input parameter. We confirm that, with or without growth, there can be both stable and unstable scenarios. To maintain stability, firms must not change their debt levels or target debt levels too quickly. Further, according to the model, the wages share is higher for zero-growth scenarios, although there are more frequent substantial drops in employment