Neuroblastoma by chance.
Ontology highlight
ABSTRACT:
SUBMITTER: Tonini GP
PROVIDER: S-EPMC6584915 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-EPMC1125898 | biostudies-literature
Project description:Seeing with two eyes usually helps one respond faster. Here we show that with ambiguous stimuli, binocular viewing can paradoxically slow down reaction time. This is explained by the observers basing their decision on a noisy neuronal representation within the visual system, with the added noise breaking the symmetry between the two possible interpretations. Binocular integration improves the representation by reducing the noise, increasing ambiguity, and decision time. The neuronal Accumulator (Race) model is applied to quantify the underlying binocular integration. The model accounts for the distributions of reaction times, and predicts suboptimal integration between eyes. We conclude that under ambiguous stimulation neuronal noise within the visual system determines responses.
| S-EPMC4649466 | biostudies-other
Project description:The estimated accuracy of a classifier is a random quantity with variability. A common practice in supervised machine learning, is thus to test if the estimated accuracy is significantly better than chance level. This method of signal detection is particularly popular in neuroimaging and genetics. We provide evidence that using a classifier's accuracy as a test statistic can be an underpowered strategy for finding differences between populations, compared to a bona fide statistical test. It is also computationally more demanding than a statistical test. Via simulation, we compare test statistics that are based on classification accuracy, to others based on multivariate test statistics. We find that the probability of detecting differences between two distributions is lower for accuracy-based statistics. We examine several candidate causes for the low power of accuracy-tests. These causes include: the discrete nature of the accuracy-test statistic, the type of signal accuracy-tests are designed to detect, their inefficient use of the data, and their suboptimal regularization. When the purpose of the analysis is the evaluation of a particular classifier, not signal detection, we suggest several improvements to increase power. In particular, to replace V-fold cross-validation with the Leave-One-Out Bootstrap.
| S-EPMC8036001 | biostudies-literature
Project description:BackgroundThe burden of cancer metastases within an individual is commonly used to clinically characterize a tumor's biological behavior. Assessments like these implicitly assume that spurious effects can be discounted. Here the influence of chance on the burden of metastasis is studied to determine whether or not this assumption is valid.MethodsMonte Carlo simulations were performed to estimate tumor burdens sustained by individuals with cancer, based upon empirically derived and validated models for the number and size distributions of metastases. Factors related to the intrinsic metastatic potential of tumors and their host microenvironments were kept constant, to more clearly demonstrate the contribution from chance.ResultsUnder otherwise identical conditions, both the simulated numbers and the sizes of metastases were highly variable. Comparable individuals could sustain anywhere from no metastases to scores of metastases, and the sizes of the metastases ranged from microscopic to macroscopic. Despite the marked variability in the number and sizes of the metastases, their respective growth times were rather more narrowly distributed. In such situations multiple occult metastases could develop into fully overt lesions within a comparatively short time period.ConclusionChance can have a major effect on the burden of metastases. Random variability can be so great as to make individual assessments of tumor biology unreliable, yet constrained enough to lead to the apparently simultaneous appearance of multiple overt metastases.
| S-EPMC1289278 | biostudies-literature
Project description:Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment. Patients were excluded if they had progressive disease (PD) during induction. Prior anti-GD2 mAb and/or I/T therapy was permitted. Each cycle, administered four weeks apart, comprised Irinotecan 50 mg/m2/day intravenously (IV) plus Temozolomide 150 mg/m2/day orally (days 1-5); naxitamab 2.25 mg/kg/day IV on days 2, 4, 8 and 10, (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously was used (days 6-10). Toxicity was measured using CTCAE v4.0 and responses through the modified International Neuroblastoma Response Criteria (INRC). Thirty-four patients (median age at treatment initiation, 4.9 years) received 164 (median 4; 1-12) HITS cycles. Toxicities included myelosuppression and diarrhea, which was expected with I/T, and pain and hypertension, expected with naxitamab. Grade ≥3-related toxicities occurred in 29 (85%) of the 34 patients; treatment was outpatient. The best responses were CR = 29% (n = 10); PR = 3% (n = 1); SD = 53% (n = 18); PD = 5% (n = 5). For cohort 1 (early treatment), the best responses were CR = 47% (n = 8) and SD = 53% (n = 9). In cohort 2 (late treatment), the best responses were CR = 12% (n = 2); PR = 6% (n = 1); SD = 53% (n = 9); and PD = 29% (n = 5). Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.
| S-EPMC10571514 | biostudies-literature
Project description:Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial. Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan-Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection. Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm. Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
| S-EPMC8006931 | biostudies-literature
Project description:The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv-vii).
| S-EPMC3402542 | biostudies-literature
Project description:Blindsight and other examples of unconscious knowledge and perception demonstrate dissociations between judgment accuracy and metacognition: Studies reveal that participants' judgment accuracy can be above chance while their confidence ratings fail to discriminate right from wrong answers. Here, we demonstrated the opposite dissociation: a reliable relationship between confidence and judgment accuracy (demonstrating metacognition) despite judgment accuracy being no better than chance. We evaluated the judgments of 450 participants who completed an AGL task. For each trial, participants decided whether a stimulus conformed to a given set of rules and rated their confidence in that judgment. We identified participants who performed at chance on the discrimination task, utilizing a subset of their responses, and then assessed the accuracy and the confidence-accuracy relationship of their remaining responses. Analyses revealed above-chance metacognition among participants who did not exhibit decision accuracy. This important new phenomenon, which we term blind insight, poses critical challenges to prevailing models of metacognition grounded in signal detection theory.
| S-EPMC4263819 | biostudies-literature
Project description:This report describes a patient with ankylosing spondylitis (AS) who underwent total hip arthroplasty (THA) by the direct anterior approach and sustained a L4-5 extension fracture dislocation with neural deficits. A magnetic resonance imaging revealed an epidural hematoma at the site of the fracture causing critical stenosis. The patient was taken to the operating room for a L3-S1 posterior decompression with L2-pelvis posterior spinal fusion. AS and diffuse idiopathic skeletal hyperostosis create a stiff spine that predisposes to fractures because of the larger moment arms experienced than normal spines. The arthroplasty surgeon performing THA should be aware and take precautions to reduce stress on the spine.
| S-EPMC5712024 | biostudies-literature
Project description:The need for replication of initial results has been rediscovered only recently in many fields of research. In preclinical biomedical research, it is common practice to conduct exact replications with the same sample sizes as those used in the initial experiments. Such replication attempts, however, have lower probability of replication than is generally appreciated. Indeed, in the common scenario of an effect just reaching statistical significance, the statistical power of the replication experiment assuming the same effect size is approximately 50%-in essence, a coin toss. Accordingly, we use the provocative analogy of "replicating" a neuroprotective drug animal study with a coin flip to highlight the need for larger sample sizes in replication experiments. Additionally, we provide detailed background for the probability of obtaining a significant p value in a replication experiment and discuss the variability of p values as well as pitfalls of simple binary significance testing in both initial preclinical experiments and replication studies with small sample sizes. We conclude that power analysis for determining the sample size for a replication study is obligatory within the currently dominant hypothesis testing framework. Moreover, publications should include effect size point estimates and corresponding measures of precision, e.g., confidence intervals, to allow readers to assess the magnitude and direction of reported effects and to potentially combine the results of initial and replication study later through Bayesian or meta-analytic approaches.
| S-EPMC6456162 | biostudies-literature