Development of Strategies for Estimating a Response Surface to Characterize a Black-box Algorithm in Terms of a White-box Algorithm

In forensic identification of source problems, there is an increasing lack of explainability of the complex black-box algorithms for the assignment of evidential value. Generally speaking, black-box algorithms are designed with prediction in mind. Although the information fed into the algorithm and the features used to make the prediction are often known to the user, the complexity of the algorithm limits the ability of the end user to understand how the input features are used. On the other hand, more transparent algorithms (sometimes referred to as “white-box”) are typically less accurate even if they provide direct information on how the input object is directly used for predicting a class or outcome. In this work, we begin the development on a response surface that characterizes the output of a black-box algorithm with the output of a white-box algorithm. Using a set of handwriting samples, we use a complex black-box algorithm across multiple features to produce a set of pairwise scores and a simple, transparent algorithm that uses individual features to produce another set of pairwise scores. A generalized least squares method is used to test the null hypothesis that there is no relationship between the two types of scores. The outcome of the significance tests helps to determine which of the individual feature scores have an influence on the black-box scores

A multisite study of performance drivers among institutional review boards.

Introduction:The time required to obtain Institutional Review Board (IRB) approval is a frequent subject of efforts to reduce unnecessary delays in initiating clinical trials. This study was conducted by and for IRB directors to better understand factors affecting approval times as a first step in developing a quality improvement framework. Methods:807 IRB-approved clinical trials from 5 University of California campuses were analyzed to identify operational and clinical trial characteristics influencing IRB approval times. Results:High workloads, low staff ratios, limited training, and the number and types of ancillary reviews resulted in longer approval times. Biosafety reviews and the need for billing coverage analysis were ancillary reviews that contributed to the longest delays. Federally funded and multisite clinical trials had shorter approval times. Variability in between individual committees at each institution reviewing phase 3 multisite clinical trials also contributed to delays for some protocols. Accreditation was not associated with shorter approval times. Conclusions:Reducing unnecessary delays in obtaining IRB approval will require a quality improvement framework that considers operational and study characteristics as well as the larger institutional regulatory environment

Uncovering a novel mechanism whereby NK cells interfere with glioblastoma virotherapy

Despite initial promising results, the success of clinical trials testing oncolytic viruses in glioblastoma patients has been limited. Innate immunity appears to be one among several barriers against successful viral oncolysis. Recent findings suggest a mechanism by which natural killer cells limit the efficacy of oncolytic viruses via natural cytotoxicity receptors

Deciphering the Multifaceted Relationship between Oncolytic Viruses and Natural Killer Cells

Despite active research in virotherapy, this apparently safe modality has not achieved widespread success. The immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. The challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. NK cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. Various reports have suggested that the NK response to oncolytic viral therapy is a critical factor in premature viral clearance while also mediating downstream antitumor immunity. As a result, particular attention should be given to the NK cell response to various oncolytic viral vectors and how their antiviral properties can be suppressed while maintaining tumor clearance. In this review we discuss the current literature on the NK response to oncolytic viral infection and how future studies clarify this intricate response

A Comparison of Labiomandibular Kinematic Durations, Displacements, Velocities, and Dysmetrias in Apraxic and Normal Adults

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Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone

a b s t r a c t Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 47 healthy comparison participants were enrolled. Participants performed a 20-min handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r = .91) of Contents lists available at ScienceDirect Human Movement Science journal homepage: www.elsevier.com /locate/humov the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients

Effects of Attentional Focus on Oral-Motor Control and Learning

Limb motor task performance is enhanced when individuals adopt an external focus (focusing on the movement effect) versus an internal focus of attention (focusing on bodily movements). The present study represents a model driven exploration of attentional focus and is the first to examine effects of attentional focus in the oral-facial system. Participants were administered a manual and oral-motor pressure accuracy task to determine whether attentional focus differences would also manifest themselves in the oral-facial system. Findings revealed an advantageous external focus during both limb and oral-motor control tasks relative to an internal focus of attention

Evidence for discrete stages of human natural killer cell differentiation in vivo

Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues

Pro- and Antiinflammatory Cytokine Signaling: Reciprocal Antagonism Regulates Interferon-gamma Production by Human Natural Killer Cells

SummaryActivated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-γ (IFN-γ) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-β, an autocrine/negative regulator of IFN-γ. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-γ for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-β signaling by downregulating the expression of the TGF-β type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-β utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-γ and T-BET, a positive regulator of IFN-γ. Indeed, activated NK cells from Smad3−/− mice produce more IFN-γ in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-γ production