Choice of Prizes Allocated by Multiple Lotteries with Endogenously Determined Probabilities

We study a class of interactive decision making situations in which each agent must choose to participate in one of several lotteries with commonly known prizes. In contrast to the widely studied paradigm of choice between gambles in individual decision making under risk, the probability of winning a prize in each of the lotteries in our study is endogenously determined. In particular, for each lottery, it is known to decrease in the number of agents choosing to play that lottery. We construct the Nash equilibrium solution to this game and then test it experimentally in the special case where each lottery yields only a single prize. The results show a remarkable degree of tacit coordination that supports the equilibrium solution under the assumption of common risk-aversion. However, this coordination is not achieved via individual level randomization. Rather, the entry decisions of most of the subjects can be characterized by local adjustments to the outcome of the previous iteration of the same game along the lines suggested by anticipatory learning models.Coordination, Endogenously Determined Probabilities

Stereotactic body radiotherapy for primary prostate cancer

Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low alpha/beta ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low-to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come

Developing a COVID-19 Medical Respite Unit for Adults Experiencing Homelessness: Lessons Learned from an Interdisciplinary Community-Academic Partnership

Individuals experiencing homelessness are at particularly high risk for infection, severe illness, and death from COVID19. Local public health initiatives to address the pandemic should include medical respite services for individuals experiencing homelessness with documented or suspected COVID-19 infection, who are well enough to not be admitted to the hospital. We are a group of public health officials, clinicians, academics, and non-profit leaders who partnered with the City of New Haven, Connecticut to develop a COVID-19 medical respite program for people experiencing homelessness in our community. We seek to describe the key processes and challenges inherent to designing the COVID-19 respite including: the balance between patient autonomy and a public health agenda, how to deliver trauma informed, equitable, patient-centered, high quality care with low resources, and approaches to program evaluation.There is no funding specific to this article. This publication was made possible by the Yale National Clinician Scholars Program and by CTSA Grant Number TL1 TR001864 from the National Center for Advancing Translational Science (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.https://deepblue.lib.umich.edu/bitstream/2027.42/155396/1/Nash main article.pdfDescription of Nash main article.pdf : Main articl

Dual- Isolation and Profiling of Circulating Tumor Cells and Cancer Exosomes from Blood Samples with Melanoma Using Immunoaffinity- Based Microfluidic Interfaces

Melanoma is among the most aggressive cancers, and its rate of incidence continues to grow. Early detection of melanoma has been hampered due to the lack of promising markers for testing. Recent advances in liquid biopsy have proposed noninvasive alternatives for cancer diagnosis and monitoring. Circulating tumor cells (CTCs) and cancer- exosomes are gaining influence as promising biomarkers because of their cancer- associated molecular markers and signatures. However, technologies that offer the dual- isolation of CTCs and exosomes using a single sample have not been thoroughly developed. The dual- utilization OncoBean (DUO) device is conjugated with melanoma specific antibodies, MCAM and MCSP, enabling simultaneous CTC and exosome isolations. Using blood samples from patients, CTCs and exosomes are specifically isolated from a single sample and then undergo molecular profiling for comprehensive study. Melanoma patients have 0- 17CTCs mL- 1 and 299 µg exosomal protein mL- 1 while healthy donors display fewer than 2CTCs and 75.6 µg of exosomes mL- 1, respectively. It is also demonstrated that both markers express melanoma- associated genes using multiplex qRT- PCR to test for expression pattern of a 96 gene panel. The dual isolation and molecular characterization will allow for further research into melanoma to identify viable markers for disease progression and treatment efficacy.Circulating tumor cells (CTCs) and cancer exosomes are gaining influence as promising biomarkers in liquid biopsy, however, technologies that offer the dual- isolation of CTCs and exosomes have not been developed. Here, a microfluidic device is devised conjugated with melanoma cell adhesion molecule (MCAM) and melanoma- associated chondroitin sulfate proteoglycan (MCSP) for isolation and molecular profiling of both melanoma CTCs and exosomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163448/3/advs1971.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163448/2/advs1971_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163448/1/advs1971-sup-0001-SuppMat.pd

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines

BACKGROUND Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design

Non-pharmacological interventions to reduce psychological distress in patients undergoing diagnostic cardiac catheterization: a rapid review

Abstract Background: Cardiac catheterization is the standard procedure for the diagnosis of coronary heart disease. The threat physically and emotionally from this procedure can effect the patient’s perception of their health. The heightened psychological distress associated with this diagnostic procedure can cause adverse patient outcomes. Non-pharmacologic interventions have been implemented to reduce psychological distress associated with cardiac catheterization. Aims: The objective of this rapid review is to assess the efficacy of non-pharmacologic interventions (procedural education, relaxation techniques, psychological preparation) on psychological distress experienced by patients as they undergo a cardiac catheterization. Methods: Published, peer-reviewed, English-language intervention studies from 1981 to 2014 were identified in a search of CINAHL, Medline, and Cochrane Library. Eligible studies included adults undergoing cardiac catheterization. Studies included in this review used experimental and quasi-experimental designs and assessed at least one primary outcome: anxiety, depression, and pain to test non-pharmacologic interventions pre and post-cardiac catheterization. Researchers independently extracted data from included studies and completed a quality assessment using a published tool. Data was synthesised as a narrative. Results: There were 29 eligible experimental and quasi-experimental studies that tested the 3 interventions (n=2504). Findings suggest that non-pharmacologic interventions were able to effectively reduce psychological distress in some patients undergoing cardiac catheterization. Conclusion: Evidence is stronger in recent studies that non-pharmacologic interventions of procedural education and psychological preparation can reduce psychological distress in patients undergoing cardiac catheterization. Further research is needed to define the various relaxation techniques that can be effectively implemented for patients undergoing cardiac catheterization

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient\u27s ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; \u3e80% cycling protocol delivery; \u3e80% outcomes measured and \u3e80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830

Stereotactic body radiotherapy for hepatocellular carcinoma: meta-analysis and International Stereotactic Radiosurgery Society practice guidelines

PURPOSE This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates following stereotactic body radiotherapy (SBRT) for liver confined hepatocellular carcinoma (HCC), and presents consensus guidelines regarding appropriate patient management. METHODS AND MATERIALS Using the Preferred Reporting Items for Systemic Review and Meta-analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published prior to October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases using the key words terms ("Stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "Stereotactic ablative radiotherapy") AND ("Hepatocellular carcinoma" OR "HCC"). An aggregated data (AD) meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, an individual patient data (IPD) analysis incorporating data from 6 institutions was conducted as its own subgroup analyses. RESULTS Seventeen observational studies, comprising 1889 HCC patients treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the AD meta-analysis. The 3- and 5- year OS rates after SBRT were 57% (95% confidence interval [CI], 47-66%) and 40% (95% CI, 29-51%). The 3- and 5- year LC rates after SBRT were 84% (95% CI, 77-90%) and 82% (95% CI, 74-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the IPD analyses. Factors prognostic for improved OS were tumor size <3 cm, eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. CONCLUSIONS SBRT is an effective treatment modality for HCC patients with mature follow up. Clinical practice guidelines were developed on behalf of the XXXX

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants