27 research outputs found
Action bias among elite soccer goalkeepers: The case of penalty kicks
In soccer penalty kicks, goalkeepers choose their action before they can clearly observe the kick direction. An analysis of 286 penalty kicks in top leagues and championships worldwide shows that given the probability distribution of kick direction, the optimal strategy for goalkeepers is to stay in the goal's center. Goalkeepers, however, almost always jump right or left. We propose the following explanation for this behavior: because the norm is to jump, norm theory (Kahneman and Miller, 1986) implies that a goal scored yields worse feelings for the goalkeeper following inaction (staying in the center) than following action (jumping), leading to a bias for action. The omission bias, a bias in favor of inaction, is reversed here because the norm here is reversed - to act rather than to choose inaction. The claim that jumping is the norm is supported by a second study, a survey conducted with 32 top professional goalkeepers. The seemingly biased decision making is particularly striking since the goalkeepers have huge incentives to make correct decisions, and it is a decision they encounter frequently. Finally, we discuss several implications of the action/omission bias for economics and management.Decision Making; Uncertainty; Choice Behavior; Sport Psychology; Behavioral Economics; Action Bias; Omission Bias; Commission Bias; Action Effect; Inaction Effect; Actor Effect; Economic Psychology; Heuristics and Biases; Soccer; Goalkeepers; Penalty Kicks; Risk; Norms
Action bias among elite soccer goalkeepers: The case of penalty kicks
In soccer penalty kicks, goalkeepers choose their action before they can clearly observe the kick direction. An analysis of 286 penalty kicks in top leagues and championships worldwide shows that given the probability distribution of kick direction, the optimal strategy for goalkeepers is to stay in the goal's center. Goalkeepers, however, almost always jump right or left. We propose the following explanation for this behavior: because the norm is to jump, norm theory (Kahneman and Miller, 1986) implies that a goal scored yields worse feelings for the goalkeeper following inaction (staying in the center) than following action (jumping), leading to a bias for action. The omission bias, a bias in favor of inaction, is reversed here because the norm here is reversed - to act rather than to choose inaction. The claim that jumping is the norm is supported by a second study, a survey conducted with 32 top professional goalkeepers. The seemingly biased decision making is particularly striking since the goalkeepers have huge incentives to make correct decisions, and it is a decision they encounter frequently. Finally, we discuss several implications of the action/omission bias for economics and management
Molecular imaging of cell death in vivo by a novel small molecule probe
Apoptosis has a role in many medical disorders, therefore assessment of apoptosis in vivo can be highly useful for diagnosis, follow-up and evaluation of treatment efficacy. ApoSense is a novel technology, comprising low molecular-weight probes, specifically designed for imaging of cell death in vivo. In the current study we present targeting and imaging of cell death both in vitro and in vivo, utilizing NST-732, a member of the ApoSense family, comprising a fluorophore and a fluorine atom, for both fluorescent and future positron emission tomography (PET) studies using an 18F label, respectively. In vitro, NST-732 manifested selective and rapid accumulation within various cell types undergoing apoptosis. Its uptake was blocked by caspase inhibition, and occurred from the early stages of the apoptotic process, in parallel to binding of Annexin-V, caspase activation and alterations in mitochondrial membrane potential. In vivo, NST-732 manifested selective uptake into cells undergoing cell-death in several clinically-relevant models in rodents: (i) Cell-death induced in lymphoma by irradiation; (ii) Renal ischemia/reperfusion; (iii) Cerebral stroke. Uptake of NST-732 was well-correlated with histopathological assessment of cell-death. NST-732 therefore represents a novel class of small-molecule detectors of apoptosis, with potential useful applications in imaging of the cell death process both in vitro and in vivo
Pancreatic cancer outcome—local treatment with radiation using MRI-LINAC
IntroductionStereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART.MethodsPatients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival.ResultsA total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2–86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8–28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1–3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups.ConclusionSMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate long-term outcome and late toxicity
ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis
Purpose: Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Methods: Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. Results: ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. Conclusion: ApoSense technology should have significant clinical utility for real-time, noninvasive detection of renal parenchymal damage of various types and evaluation of its distribution and magnitude; it may facilitate the assessment of efficacy of therapeutic interventions in a broad spectrum of disease states
Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2.
Prostaglandin (PG) E(1) has been shown to possess anti-inflammatory properties and to modulate vascular reactivity. These activities are sometimes distinct from those of PGE(2), suggesting that endogenously produced PGE(1) may have some beneficial therapeutic effects compared with PGE(2). Increasing the endogenous formation of PGE(1) requires optimization of two separate processes, namely, enrichment of cellular lipids with dihomo-gamma-linolenic acid (20:3 n-6; DGLA) and effective cyclo-oxygenase-dependent oxygenation of substrate DGLA relative to arachidonic acid (AA; 20:4 n-6). DGLA and AA had similar affinities (K(m) values) and maximal reaction rates (V(max)) for cyclo-oxygenase-2 (COX-2), whereas AA was metabolized preferentially by cyclo-oxygenase-1 (COX-1). To overcome the kinetic preference of COX-1 for AA, CP-24879, a mixed Delta(5)/Delta(6) desaturase inhibitor, was used to enhance preferential accumulation of DGLA over AA in cells cultured in the presence of precursor gamma-linolenic acid (18:3 n-6). This protocol was tested in two cell lines and both yielded a DGLA/AA ratio of approx. 2.8 in the total cellular lipids. From the enzyme kinetic data, it was calculated that this ratio should offset the preference of COX-1 for AA over DGLA. PGE(1) synthesis in the DGLA-enriched cells was increased concurrent with a decline in PGE(2) formation. Nevertheless, PGE(1) synthesis was still substantially lower than that of PGE(2). It appears that employing a dietary or a combined dietary/pharmacological paradigm to augment the cellular ratio of DGLA/AA is not an effective route to enhance endogenous synthesis of PGE(1) over PGE(2), at least in cells/tissues where COX-1 predominates over COX-2
Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions
T cells expressing chimeric antigen receptors (CARs) are at the forefront of clinical treatment of cancers. Still, the nanoscale organization of CARs at the interface of CAR-Ts with target cells, which is essential for TCR-mediated T cell activation, remains poorly understood. Here, we studied the nanoscale organization of CARs targeting CD138 proteoglycans in such fixed and live interfaces, generated optimally for single-molecule localization microscopy. CARs showed significant self-association in nanoclusters that was enhanced in interfaces with on-target cells (SKOV-3, CAG, FaDu) relative to negative cells (OVCAR-3). CARs also segregated more efficiently from the abundant membrane phosphatase CD45 in CAR-T cells forming such interfaces. CAR clustering and segregation from CD45 correlated with the effector functions of Ca++ influx and target cell killing. Our results shed new light on the nanoscale organization of CARs on the surfaces of CAR-Ts engaging on- and off-target cells, and its potential significance for CAR-Ts’ efficacy and safety