The LHC Olympics 2020 a community challenge for anomaly detection in high energy physics.

A new paradigm for data-driven, model-agnostic new physics searches at colliders is emerging, and aims to leverage recent breakthroughs in anomaly detection and machine learning. In order to develop and benchmark new anomaly detection methods within this framework, it is essential to have standard datasets. To this end, we have created the LHC Olympics 2020, a community challenge accompanied by a set of simulated collider events. Participants in these Olympics have developed their methods using an R&D dataset and then tested them on black boxes: datasets with an unknown anomaly (or not). Methods made use of modern machine learning tools and were based on unsupervised learning (autoencoders, generative adversarial networks, normalizing flows), weakly supervised learning, and semi-supervised learning. This paper will review the LHC Olympics 2020 challenge, including an overview of the competition, a description of methods deployed in the competition, lessons learned from the experience, and implications for data analyses with future datasets as well as future colliders.

Serotonin transporter occupancy and the functional neuroanatomic effects of citalopram in geriatric depression.

OBJECTIVES: The functional neuroanatomic changes associated with selective serotonin reuptake inhibitor (SSRI) treatment have been the focus of positron emission tomography (PET) studies of cerebral glucose metabolism in geriatric depression. DESIGN: To evaluate the underlying neurochemical mechanisms, both cerebral glucose metabolism and serotonin transporter (SERT) availability were measured before and during treatment with the SSRI, citalopram. It was hypothesized that SERT occupancy would be observed in cortical and limbic brain regions that have shown metabolic effects, as well as striatal and thalamic regions that have been implicated in prior studies in midlife patients. SETTING: Psychiatric outpatient clinic. PARTICIPANTS: Seven depressed patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for current major depressive episode were enrolled. INTERVENTION: Patients underwent a 12-week open-label trial of the SSRI, citalopram. MEASUREMENTS: Patients underwent high-resolution research tomography PET scans to measure changes in cerebral glucose metabolism and SERT occupancy by citalopram treatment (after 8-10 weeks of treatment). RESULTS: Three different tracer kinetic models were applied to the [¹¹C]-DASB region-of-interest data and yielded similar results of an average of greater than 70% SERT occupancy in the striatum and thalamus during citalopram treatment. Voxel-wise analyses showed significant SERT occupancy in these regions, as well as cortical (e.g., anterior cingulate, superior and middle frontal, precuneus, and limbic (parahippocampal gyrus) areas that also showed reductions in glucose metabolism. CONCLUSION: The findings suggest that cortical and limbic SERT occupancy may be an underlying mechanism for the regional cerebral metabolic effects of citalopram in geriatric depression.

Translocator Protein Distribution Volume Predicts Reduction of Symptoms During Open-Label Trial of Celecoxib in Major Depressive Disorder.

BACKGROUND: Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis and response to therapeutics targeting effects of gliosis is largely unknown. Translocator protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction of depressive symptoms following open-label celecoxib administration in treatment-resistant major depressive disorder. METHODS: A total of 41 subjects with treatment-resistant major depressive disorder underwent one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS). RESULTS: Cumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively. CONCLUSIONS: Celecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO VT on symptom reduction, this personalized medicine approach of matching a marker of gliosis to medication targeting effects of gliosis should be applied in early development of novel therapeutics, in particular for treatment-resistant major depressive disorder.

Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder.

Importance: For a small percentage of obsessive-compulsive disorder (OCD) cases exhibiting additional neuropsychiatric symptoms, it was proposed that neuroinflammation occurs in the basal ganglia as an autoimmune response to infections. However, it is possible that elevated neuroinflammation, inducible by a diverse range of mechanisms, is important throughout the cortico-striato-thalamo-cortical circuit of OCD. Identifying brain inflammation is possible with the recent advance in positron emission tomography (PET) radioligands that bind to the translocator protein (TSPO). Translocator protein density increases when microglia are activated during neuroinflammation and the TSPO distribution volume (VT) is an index of TSPO density. Objective: To determine whether TSPO VT is elevated in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex in OCD. Design, Setting, and Participants: This case-control study was conducted at a tertiary care psychiatric hospital from May 1, 2010, to November 30, 2016. Participants with OCD (n = 20) and age-matched healthy control individuals (n = 20) underwent a fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET scan. It is a high-quality second-generation TSPO-binding PET radiotracer. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures: The TSPO VT was measured in the dorsal caudate, orbitofrontal cortex, thalamus, ventral striatum, dorsal putamen, and anterior cingulate cortex. Compulsions were assessed with the Yale-Brown Obsessive Compulsive Scale. Results: In the OCD and healthy groups, the mean (SD) ages were 27.4 (7.1) years and 27.6 (6.6) years, respectively, and 11 (55%) and 8 (40%) were women, respectively. In OCD, TSPO VT was significantly elevated in these brain regions (mean, 32%; range, 31%-36% except anterior cingulate cortex, 24%; analysis of variance, effect of diagnosis: P < .001 to P = .004). Slightly lower elevations in TSPO VT (22%-29%) were present in other gray matter regions. The Yale-Brown Obsessive Compulsive Scale measure of distress associated with preventing compulsive behaviors significantly correlated with TSPO VT in the orbitofrontal cortex (uncorrected Pearson correlation r = 0.62; P = .005). Conclusions and Relevance: To our knowledge, this is the first study demonstrating inflammation within the neurocircuitry of OCD. The regional distribution of elevated TSPO VT argues that the autoimmune/neuroinflammatory theories of OCD should extend beyond the basal ganglia to include the cortico-striato-thalamo-cortical circuit. Immunomodulatory therapies should be investigated in adult OCD, rather than solely childhood OCD, particularly in cases with prominent distress when preventing compulsions.

A polymeric membrane dressing with antinociceptive properties: analysis with a rodent model of stab wound secondary hyperalgesia.

UNLABELLED: The putative antinociceptive properties of a commercially available polymeric membrane dressing were tested by using a hind limb penetrating stab wound model in which secondary hyperalgesia could be evaluated from the hind paw. We examined the responses to mechanical and thermal stimuli applied to the hind paw remote to 2 small penetrating stab wounds of the calf. Application of the polymeric membrane dressing, but not gauze dressing, significantly reduced the development of both mechanical and thermal hyperalgesia induced by the penetrating stab wounds. In addition, animals with stab wounds showed a significant decrease in cage activity, and this decrease was prevented by application of the polymeric dressing. Analysis of spinal cord Fos expression demonstrated that the polymeric membrane, but not gauze, dressing significantly decreased stab wound-induced Fos expression in laminae I to VI of the ipsilateral L3-L5 cord segments. In addition, application of the polymeric membrane, but not gauze, dressing to the hind limb of naïve animals elicited Fos expression in laminae III and IV of the lumbar spinal cord. The data indicate that this model might be useful for evaluation of the mechanisms underlying deep tissue injury-induced secondary hyperalgesia, but they also demonstrate that the polymeric membrane dressing tested is capable of significantly reducing secondary hyperalgesia. PERSPECTIVE: Surgery and other types of penetrating wounds cause pain that is not always relieved by opioids and/or less potent analgesics. The present results suggest that the polymeric membrane dressing tested here may be used alone or in conjunction with analgesics to relieve pain caused by penetrating tissue injury.

Narrowband auscultatory blood pressure measurement.

Auscultatory blood pressure measurement uses the presence and absence of acoustic pulses generated by an artery (i.e., Korotkoff sound), detected with a stethoscope or a sensitive microphone, to noninvasively estimate systolic and diastolic pressures. Unfortunately, in high noise situations, such as ambulatory environments or when the patient moves moderately, the current auscultatory blood pressure method is unreliable, if at all possible. Empirical evidence suggests that the pulse beneath an artery occlusion travels relatively slow compared with the speed of sound. By placing two microphones along the bicep muscle near the brachial artery under the occlusion cuff, a similar blood pressure pulse appears in the two microphones with a relative time delay. The acoustic noise, on the other hand, appears in both microphones simultaneously. The contribution of this paper is to utilize this phenomenon by filtering the microphone waveforms to create spatially narrowband information signals. With a narrowband signal, the microphone signal phasing information is adequate for distinguishing between acoustic noise and the blood pressure pulse. By choosing the microphone spacing correctly, subtraction of the two signals will enhance the information signal and cancel the noise signal. The general spacing problem is also presented.