Automatic Passenger Counting: Introducing the t-Test Induced Equivalence Test

Automatic passenger counting (APC) in public transport has been introduced in the 1970s and has been rapidly emerging in recent years. Still, real-world applications continue to face events that are difficult to classify. The induced imprecision needs to be handled as statistical noise and thus methods have been defined to ensure that measurement errors do not exceed certain bounds. Various recommendations for such an APC validation have been made to establish criteria that limit the bias and the variability of the measurement errors. In those works, the misinterpretation of non-significance in statistical hypothesis tests for the detection of differences (e.g. Student's t-test) proves to be prevalent, although existing methods which were developed under the term equivalence testing in biostatistics (i.e. bioequivalence trials, Schuirmann in J Pharmacokinet Pharmacodyn 15(6):657-680, 1987) would be appropriate instead. This heavily affects the calibration and validation process of APC systems and has been the reason for unexpected results when the sample sizes were not suitably chosen: Large sample sizes were assumed to improve the assessment of systematic measurement errors of the devices from a user's perspective as well as from a manufacturer's perspective, but the regular t-test fails to achieve that. We introduce a variant of the t-test, the revised t-test, which addresses both type I and type II errors appropriately and allows a comprehensible transition from the long-established t-test in a widely used industrial recommendation. This test is appealing, but still it is susceptible to numerical instability. Finally, we analytically reformulate it as a numerically stable equivalence test, which is thus easier to use. Our results therefore allow to induce an equivalence test from a t-test and increase the comparability of both tests, especially for decision makers.Comment: 15 pages, 2 figures. Transportation (2019

Exact change point detection with improved power in small‐sample binomial sequences

To detect a change in the probability of a sequence of independent binomial random variables, a variety of asymptotic and exact testing procedures have been proposed. Whenever the sample size or the event rate is small, asymptotic approximations of maximally selected test statistics have been shown to be inaccurate. Although exact methods control the type I error rate, they can be overly conservative due to the discreteness of the test statistics in these situations. We extend approaches by Worsley and Halpern to develop a test that is less discrete to increase the power. Building on ideas from binary segmentation, the proposed test utilizes unused information in the binomial sequences to add a new ordering to test statistics that are of equal value. The exact distributions are derived under side conditions that arise in hypothetical segmentation steps and do not depend on the type of test statistic used (e.g., log likelihood ratio, cumulative sum, or Fisher's exact test). Using the proposed exact segmentation procedure, we construct a change point test and prove that it controls the type‐I‐error rate at any given nominal level. Furthermore, we prove that the new test is uniformly at least as powerful as Worsley's exact test. In a Monte Carlo simulation study, the gain in power can be remarkable, especially in scenarios with small sample size. Giving a clinical database example about pin site infections and an example assessing publication bias in neuropsychiatric drug research, we demonstrate the wide‐ranging applicability of the test

The N-Terminal domain of SIRT1 is a positive regulator of endogenous SIRT1-dependent deacetylation and transcriptional outputs

SummaryThe NAD+-dependent protein deacetylase SIRT1 regulates energy metabolism, responses to stress, and aging by deacetylating many different proteins, including histones and transcription factors. The mechanisms controlling SIRT1 enzymatic activity are complex and incompletely characterized, yet essential for understanding how to develop therapeutics that target SIRT1. Here, we demonstrate that the N-terminal domain of SIRT1 (NTERM) can trans-activate deacetylation activity by physically interacting with endogenous SIRT1 and promoting its association with the deacetylation substrate NF-κB p65. Two motifs within the NTERM domain contribute to activation of SIRT1-dependent activities, and expression of one of these motifs in mice is sufficient to lower fasting glucose levels and improve glucose tolerance in a manner similar to overexpression of SIRT1. Our results provide insights into the regulation of SIRT1 activity and a rationale for pharmacological control of SIRT1-dependent activities

Multiomics Longitudinal Modeling of Preeclamptic Pregnancies

Preeclampsia is a complex disease of pregnancy whose physiopathology remains unclear and that poses a threat to both mothers and infants. Specific complex changes in women\u27s physiology precede a diagnosis of preeclampsia. Understanding multiple aspects of such a complex changes at different levels of biology, can be enabled by simultaneous application of multiple assays. We developed prediction models for preeclampsia risk by analyzing six omics datasets from a longitudinal cohort of pregnant women. A machine learning-based multiomics model had high accuracy (area under the receiver operating characteristics curve (AUC) of 0.94, 95% confidence intervals (CI):[0.90, 0.99]). A prediction model using only ten urine metabolites provided an accuracy of the whole metabolomic dataset and was validated using an independent cohort of 16 women (AUC= 0.87, 95% CI:[0.76, 0.99]). Integration with clinical variables further improved prediction accuracy of the urine metabolome model (AUC= 0.90, 95% CI:[0.80, 0.99], urine metabolome, validated). We identified several biological pathways to be associated with preeclampsia. The findings derived from models were integrated with immune system cytometry data, confirming known physiological alterations associated with preeclampsia and suggesting novel associations between the immune and proteomic dynamics. While further validation in larger populations is necessary, these encouraging results will serve as a basis for a simple, early diagnostic test for preeclampsia

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

Synaptic and Intrinsic Activation of GABAergic Neurons in the Cardiorespiratory Brainstem Network

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in close apposition to cardioinhibitory parasympathetic cardiac neurons in the nucleus ambiguus (NA). These neurons fire in synchronization with inspiratory activity. Although they receive excitatory glutamatergic synaptic inputs during inspiration, this excitatory neurotransmission was not altered by blocking nicotinic receptors, and many of these GABAergic neurons continue to fire after synaptic blockade. The spontaneous firing in these GABAergic neurons was not altered by the voltage-gated calcium channel blocker cadmium chloride that blocks both neurotransmission to these neurons and voltage-gated Ca2+ currents, but spontaneous firing was diminished by riluzole, demonstrating a role of persistent sodium channels in the spontaneous firing in these cardiorespiratory GABAergic neurons that possess a pacemaker phenotype. The spontaneously firing GABAergic neurons identified in this study that increase their activity during inspiration would support respiratory rhythm generation if they acted primarily to inhibit post-inspiratory neurons and thereby release inspiration neurons to increase their activity. This population of inspiratory-modulated GABAergic neurons could also play a role in inhibiting neurons that are most active during expiration and provide a framework for respiratory sinus arrhythmia as there is an increase in heart rate during inspiration that occurs via inhibition of premotor parasympathetic cardioinhibitory neurons in the NA during inspiration

Phase 1 Safety and Immunogenicity Evaluation of ADVAX, a Multigenic, DNA-Based Clade C/B' HIV-1 Candidate Vaccine

BACKGROUND: We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers. METHODOLOGY/PRINCIPAL FINDINGS: ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur. CONCLUSIONS/SIGNIFICANCE: ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses. TRIAL REGISTRATION: Clinicaltrials.gov NCT00249106.published_or_final_versio

Psychodynamic Experience Enhances Recognition of Hidden Childhood Trauma

BACKGROUND: Experimental psychology has only recently provided supporting evidence for Freud's and Janet's description of unconscious phenomena. Here, we aimed to assess whether specific abilities, such as personal psychodynamic experience, enhance the ability to recognize unconscious phenomena in peers - in other words, to better detect implicit knowledge related to individual self-experience. METHODOLOGY AND PRINCIPAL FINDINGS: First, we collected 14 videos from seven healthy adults who had experienced a sibling's cancer during childhood and seven matched controls. Subjects and controls were asked to give a 5-minute spontaneous free-associating speech following specific instructions created in order to activate a buffer zone between fantasy and reality. Then, 18 raters (three psychoanalysts, six medical students, three oncologists, three cognitive behavioral therapists and three individuals with the same experience of trauma) were randomly shown the videos and asked to blindly classify them according to whether the speaker had a sibling with cancer using a Likert scale. Using a permutation test, we found a significant association between group and recognition score (ANOVA: p = .0006). Psychoanalysts were able to recognize, above chance levels, healthy adults who had experienced sibling cancer during childhood without explicit knowledge of this history (Power = 88%; p = .002). In contrast, medical students, oncologists, cognitive behavioral therapists and individuals who had the same history of a sibling's cancer were unable to do so. CONCLUSION: This experiment supports the view that implicit recognition of a subject's history depends on the rater's specific abilities. In the case of subjects who did have a sibling with cancer during childhood, psychoanalysts appear better able to recognize this particular history

Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS. METHODS: This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires. RESULTS: Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients. CONCLUSION: CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management