Sequential All-Pay Auctions with Head Starts and Noisy Outputs

We study a sequential (Stackelberg) all-pay auction with two contestants who are privately informed about a parameter (ability) that affects their cost of effort. Contestant 1 (the fi?rst mover) exerts an effort in the fi?rst period, while contestant 2 (the second mover) observes the effort of contestant 1 and then exerts an effort in the second period. Contestant 2 wins the contest if his effort is larger than or equal to the effort of contestant 1; otherwise, contestant 1 wins. We characterize the unique subgame perfect equilibrium of this sequential all-pay auction and analyze the use of head starts to improve the contestants' performances. We also study this model when contestant 1 exerts an effort in the fi?rst period which translates into an observable output but with some noise. We study two variations of this model where contestant 1 either knows or does not know the realization of the noise before she chooses her effort. Contestant 2 does not know the realization of the noise in both variations. For both variations, we characterize the subgame perfect equilibrium and investigate the effect of a random noise on the contestants' performance.Sequential all-pay auctions, head starts, noisy outputs.

The Medical Necessity for Medicinal Cannabis: Prospective, Observational Study Evaluating the Treatment in Cancer Patients on Supportive or Palliative Care

Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6–8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P<0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P=0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients

Sequential All-Pay Auctions with Head Starts

We study a sequential all-pay auction where heterogeneous contestants are privately informed about a parameter (ability) that affects their cost of effort. In the case of two contestants, contestant 1 (the first mover) makes an effort in the first period, while contestant 2 (the second mover) observes the effort of contestant 1 and then makes an effort in the second period. Contestant 2 wins the contest if his effort is larger than or equal to the effort of contestant 1; otherwise, contestant 1 wins. This model is then generalized to any number of contestants where in each period of the contest, 1 /all-pay auctions; head starts; Sequential contests

Sequential All-Pay Auctions with Noisy Outputs

We study a sequential all-pay auction with two contestants who are privately informed about a parameter (ability) that affects their cost of effort. In the model, contestant 1 (the first mover) exerts an effort in the first period which translates into an observable output but with some noise, and contestant 2 (the second mover) observes this noisy output. Then, contestant 2 exerts an effort in the second period, and wins the contest if her output is larger than or equal to the observed noisy output of contestant 1; otherwise, contestant 1 wins. We study two variations of this model where contestant 1 either knows or does not know the realization of the noise before she chooses her effort. Contestant 2 does not know the realization of the noise in both variations. For both variations, we characterize the subgame perfect equilibrium and investigate the effect of a random noise on the expected highest effort in this contest.Noisy outputs; Sequential contests

National Scale Real-Time Surveillance of SARS-CoV-2 Variants Dynamics by Wastewater Monitoring in Israel

In this report, we describe a national-scale monitoring of the SARS-CoV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of 13 wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19/A20 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December 2020 and March 2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021 and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February&ndash;March 2021. This study demonstrates the importance of monitoring SC-2 variant by using a combination of inclusive and selective PCR tests on a national scale through wastewater sampling, which is far more amendable for high-throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1, BA.2) and other variants

Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes—exploratory analysis of the Clalit registry

Abstract Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a ‘study-cohort’ (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a ‘general 21-gene-tested BC-cohort’ (2044 previously described N0/N1mi/N1 patients). The median time between the first and second BC was 5.2 (IQR, 3.1–7.1) years; the second BC was ipsilateral in 68%. Patient/tumor characteristics of the first- and second-BC in the ‘study-cohort’ were similar, except for the RS which was higher in the second BC (median [IQR]: 23 [17–30] vs 17 [14–22], p < 0.001). Overall, 56 patients had follow-up data, of whom 5 experienced distant recurrence (2 RS 11–25 patients and 3 RS 26–100 patients). Studies exploring the prognostic utility of the RS in this setting are warranted

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome

DataSheet_1_Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy.pdf

IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.</p