A measurement of the equation of state of carbon envelopes of white dwarfs.

White dwarfs represent the final state of evolution for most stars1-3. Certain classes of white dwarfs pulsate4,5, leading to observable brightness variations, and analysis of these variations with theoretical stellar models probes their internal structure. Modelling of these pulsating stars provides stringent tests of white dwarf models and a detailed picture of the outcome of the late stages of stellar evolution6. However, the high-energy-density states that exist in white dwarfs are extremely difficult to reach and to measure in the laboratory, so theoretical predictions are largely untested at these conditions. Here we report measurements of the relationship between pressure and density along the principal shock Hugoniot (equations describing the state of the sample material before and after the passage of the shock derived from conservation laws) of hydrocarbon to within five per cent. The observed maximum compressibility is consistent with theoretical models that include detailed electronic structure. This is relevant for the equation of state of matter at pressures ranging from 100 million to 450 million atmospheres, where the understanding of white dwarf physics is sensitive to the equation of state and where models differ considerably. The measurements test these equation-of-state relations that are used in the modelling of white dwarfs and inertial confinement fusion experiments7,8, and we predict an increase in compressibility due to ionization of the inner-core orbitals of carbon. We also find that a detailed treatment of the electronic structure and the electron degeneracy pressure is required to capture the measured shape of the pressure-density evolution for hydrocarbon before peak compression. Our results illuminate the equation of state of the white dwarf envelope (the region surrounding the stellar core that contains partially ionized and partially degenerate non-ideal plasmas), which is a weak link in the constitutive physics informing the structure and evolution of white dwarf stars9.

Attosecond Real-Time Observation of Recolliding Electron Trajectories in Helium at Low Laser Intensities.

Laser-driven recollision physics is typically accessible only at field intensities high enough for tunnel ionization. Using an extreme ultraviolet pulse for ionization and a near-infrared (NIR) pulse for driving of the electron wave packet lifts this limitation. This allows us to study recollisions for a broad range of NIR intensities with transient absorption spectroscopy, making use of the reconstruction of the time-dependent dipole moment. Comparing recollision dynamics with linear vs circular NIR polarization, we find a parameter space, where the latter favors recollisions, providing evidence for the so far only theoretically predicted recolliding periodic orbits.

Characteristics and treatment outcome of suicidal depression: Two large naturalistic cohorts of depressed outpatients.

OBJECTIVE: The emergence of new drugs for managing suicidal ideation (e.g. ketamine) raises the question of whether suicidal depression (i.e. moderate to severe depression with concomitant suicidal ideation) is a specific depression phenotype. Therefore, this study characterized patients with suicidal depression (baseline clinical characteristics, suicidal ideation and depression evolutions, suicide risk) in two large cohorts of outpatients with depression. METHODS: LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with depression (Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria), treated and followed up for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale, and suicidal ideation with the suicidal item of the Montgomery-Åsberg Depression Rating Scale. Patients with moderate or severe depression (Hospital Anxiety and Depression Scale-Depression subscale score >11) were selected and classified as without suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale <2), with moderate suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale [2; 3]) and with severe suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale ⩾4). RESULTS: Baseline clinical features were more severe (e.g. higher anxiety and depression scores) in depressed patients with moderate/severe suicidal ideation. Depression remission after treatment was less frequent among patients with severe suicidal ideation. The risk of suicide attempt during the follow-up was threefold higher in patients with suicidal ideation among those 10% had persistent suicidal ideation. CONCLUSION: Suicidal depression could be a specific depression phenotype with more severe clinical characteristics, less frequent depression remission, suicidal ideation persistence and higher suicide attempt risk, despite antidepressant treatment. It seems that novel therapeutic strategies could be needed.

In vivo hippocampal cornu ammonis 1-3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes.

OBJECTIVE: Previous positron emission tomography (PET) studies using [11 C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [11 C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes. METHODS: We obtained magnetic resonance imaging (MRI) and [11 C]ABP688-PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI-derived anatomical subfields were combined into CA1-3, CA4/dentate gyrus, and Subiculum. Partial volume corrected [11 C]ABP688 nondisplaceable binding potential (BPND ) values were averaged across each subfield, and Z-scores were calculated. Subfield [11 C]ABP688-BPND was compared between seizure-free and non-seizure-free patients. In addition, we also assessed subfield volumes and [18 F]fluorodeoxyglucose (FDG) uptake in each clinical group. RESULTS: MTLE [11 C]ABP688-BPND was reduced in ipsilateral (epileptogenic) CA1-3 and CA4/dentate-gyrus (p < .001, 95% confidence interval [CI] = .29-.51) compared to controls, with no difference in Subiculum. [11 C]ABP688-BPND and subfield volumes were compared between seizure-free (Engel IA, n = 13) and non-seizure-free patients (Engel IC-III, n = 10). In ipsilateral CA1-3 only, [11 C]ABP688-BPND was lower in seizure-free patients than in non-seizure-free patients (p = .012, 95% CI = 1.46-11.0) independently of volume. A subset analysis of 12 patients with [11 C]ABP688-PET+[18 F]FDG-PET showed no between-group significant difference in [18 F]FDG uptake, whereas CA1-3 [11 C]ABP688-BPND remained significantly lower in the seven of 12 seizure-free patients (p = .03, 95% CI = -3.13 to -.21). SIGNIFICANCE: Reduced mGluR5 allosteric site availability in hippocampal CA1-3, measured in vivo by [11 C]ABP688-PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1-3 [11 C]ABP688-PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI-negative/PET-negative MTLE patients.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Characterization of depressed bipolar patients with current suicidal ideation.

OBJECTIVE: Bipolar disorder is one of the most frequent psychiatric disorders among suicidal patients. A large part of patients with bipolar disorder (30-50%) will attempt suicide. Suicidal ideation being a major risk factor of suicidal act, it is crucial to better characterize patients with suicidal bipolar depression (i.e. depression with current suicidal ideation). The aim of this study was to characterize suicidal bipolar depressed patients in comparison with non-suicidal depressed patients in terms of clinical characteristics, evolution of depression and suicidal ideation course over time, and risk of suicide attempt during follow-up. METHODS: Among patients with bipolar disorder recruited from the network of FondaMental expert centres for bipolar disorder between 2009 and 2017, we selected patients with at least mild depression (Montgomery-Åsberg Depression Rating Scale total score >11) and without current manic symptomatology (Young Mania Rating Scale total score <7) at baseline (N = 938). Suicidal depression was defined by a baseline score ⩾2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report (N = 271, 28.9%). Non-suicidal depression was defined by a baseline item 12 of the Quick Inventory of Depressive Symptomatology-Self Report score <2 (N = 667, 71.1%). A subsample of about 300 patients (with or without suicidal ideation at baseline) was followed up for 2 years. RESULTS: Baseline clinical features (e.g. depression severity, childhood trauma, global functioning) were more severe in patients with than without suicidal depression. Suicidal patients tended to remain more suicidal throughout the follow-up than patients without suicidal ideation at baseline (3.4-fold higher risk of persistent suicidal ideation at the 2-year visit despite an improvement in depressive symptomatology). CONCLUSIONS: Depressed bipolar disorder patients reporting suicidal ideation had more severe clinical features at baseline and were more prone to report persistent suicidal ideation during the follow-up, independently of thymic state. Clinicians should closely monitor this subgroup of patients.

Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study.

BACKGROUND: There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. METHODS: This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load <50 copies/mL, and lymphocyte T-CD4 level ≥200 cells/µL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in ≥2 neurocognitive domains were secondary outcomes of NCI. RESULTS: Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/µL, and median nadir T-CD4 lymphocyte level was 176 cells/µL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). CONCLUSIONS: In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications. CLINICAL TRIALS REGISTRATION: NCT02592174.

In vivo metabotropic glutamate receptor type 5 abnormalities localize the epileptogenic zone in mesial temporal lobe epilepsy.

OBJECTIVE: Surgical specimens from patients with mesial temporal lobe epilepsy (MTLE) show abnormalities in tissue concentrations of metabotropic glutamate receptor type 5 (mGluR5). To clarify whether these abnormalities are specific to the epileptogenic zone (EZ), we characterized in vivo whole-brain mGluR5 availability in MTLE patients using positron emission tomography (PET) and [11 C]ABP688, a radioligand that binds specifically to the mGluR5 allosteric site. METHODS: Thirty-one unilateral MTLE patients and 30 healthy controls underwent [11 C]ABP688 PET. We compared partial volume corrected [11 C]ABP688 nondisplaceable binding potentials (BPND ) between groups using region-of-interest and whole-brain voxelwise analyses. [18 F]Fluorodeoxyglucose (FDG) PET was acquired in 15 patients, for whom we calculated asymmetry indices of [11 C]ABP688 BPND and [18 F]FDG uptake to compare lateralization and localization differences. RESULTS: [11 C]ABP688 BPND was focally reduced in the epileptogenic hippocampal head and amygdala (p < 0.001). Patients with hippocampal atrophy showed more extensive abnormalities, including the ipsilateral temporal neocortex (p = 0.006). [11 C]ABP688 BPND showed interhemispheric differences of higher magnitude and discriminated the epileptogenic structures more accurately when compared to [18 F]FDG uptake, which showed more widespread hypometabolism. Among 23 of 25 operated patients with >1 year of follow-up, 13 were seizure-free (Engel Ia) and showed significantly lower [11 C]ABP688 BPND in the ipsilateral entorhinal cortex. INTERPRETATION: [11 C]ABP688 PET provides a focal biomarker for the EZ in MTLE with higher spatial accuracy compared to [18 F]FDG PET. Focally reduced mGluR5 availability in the EZ might reflect receptor internalization or conformational changes in response to excessive extracellular glutamate, supporting a potential role for mGluR5 as therapeutic target in human MTLE. Ann Neurol 2019; 1-11 ANN NEUROL 2019;85:218-228.

High-Fidelity Software-Defined Quantum Logic on a Superconducting Qudit.

We present an efficient approach to achieving arbitrary, high-fidelity control of a multilevel quantum system using optimal control techniques. As an demonstration, we implement a continuous, software-defined microwave pulse to realize a 0↔2 SWAP gate that achieves an average gate fidelity of 99.4%. We describe our procedure for extracting the system Hamiltonian, calibrating the quantum and classical hardware chain, and evaluating the gate fidelity. Our work represents an alternative, fully generalizable route towards achieving universal quantum control by leveraging optimal control techniques.

Onset of a Two-Dimensional Superconducting Phase in a Topological-Insulator-Normal-Metal Bi_{1-x}Sb_{x}/Pt Junction Fabricated by Ion-Beam Techniques.

Inducing superconductivity in a topological insulator can lead to novel quantum effects. However, experimental approaches to turn a topological insulator into a superconductor are limited. Here, we report on superconductivity in topological insulator Bi_{0.91}Sb_{0.09} induced via focused ion-beam deposition of a Pt thin film. The superconducting phase exhibits a Berezinski-Kosterlitz-Thouless transition, demonstrative of its two-dimensional character. From the in-plane upper critical field measurements, we estimate the superconducting thickness to be ∼17 nm for a 5.5-µm-thick sample. Our results provide evidence that the interface superconductivity could originate from the surface states of Bi_{0.91}Sb_{0.09}.

rNAV 2.0: a visualization tool for bacterial sRNA-mediated regulatory networks mining.

BACKGROUND: Bacterial sRNA-mediated regulatory networks has been introduced as a powerful way to analyze the fast rewiring capabilities of a bacteria in response to changing environmental conditions. The identification of mRNA targets of bacterial sRNAs is essential to investigate their functional activities. However, this step remains challenging with the lack of knowledge of the topological and biological constraints behind the formation of sRNA-mRNA duplexes. Even with the most sophisticated bioinformatics target prediction tools, the large proportion of false predictions may be prohibitive for further analyses. To deal with this issue, sRNA target analyses can be carried out from the resulting gene lists given by RNA-SEQ experiments when available. However, the number of resulting target candidates may be still huge and cannot be easily interpreted by domain experts who need to confront various biological features to prioritize the target candidates. Therefore, novel strategies have to be carried out to improve the specificity of computational prediction results, before proposing new candidates for an expensive experimental validation stage. RESULT: To address this issue, we propose a new visualization tool rNAV 2.0, for detecting and filtering bacterial sRNA targets for regulatory networks. rNAV is designed to cope with a variety of biological constraints, including the gene annotations, the conserved regions of interaction or specific patterns of regulation. Depending on the application, these constraints can be variously combined to analyze the target candidates, prioritized for instance by a known conserved interaction region, or because of a common function. CONCLUSION: The standalone application implements a set of known algorithms and interaction techniques, and applies them to the new problem of identifying reasonable sRNA target candidates.

Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.

Characterization of age/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [(11)C]ABP688 PET.

PURPOSE: Metabotropic glutamate receptor type 5 (mGluR5) is a G protein-coupled receptor that has been implicated in several psychiatric and neurological diseases. The radiopharmaceutical [(11)C]ABP688 allows for in vivo quantification of mGluR5 availability using positron emission tomography (PET). In this study, we aimed to detail the regional distribution of [(11)C]ABP688 binding potential (BPND) and the existence of age/sex effects in healthy individuals. METHODS: Thirty-one healthy individuals aged 20 to 77 years (men, n = 18, 45.3 ± 18.2 years; females, n = 13, 41.5 ± 19.6 years) underwent imaging with [(11)C]ABP688 using the high-resolution research tomograph (HRRT). We developed an advanced partial volume correction (PVC) method using surface-based analysis in order to accurately estimate the regional variation of radioactivity. BPND was calculated using the simplified reference tissue model, with the cerebellum as the reference region. Surface-based and volume-based analyses were performed for 39 cortical and subcortical regions of interest per hemisphere. RESULTS: We found the highest [(11)C]ABP688 BPND in the lateral prefrontal and anterior cingulate cortices. The lowest [(11)C]ABP688 BPND was observed in the pre- and post-central gyri as well as the occipital lobes and the thalami. No sex effect was observed. Associations between age and [(11)C]ABP688 BPND without PVC were observed in the right amygdala and left putamen, but were not significant after multiple comparisons correction. CONCLUSIONS: The present results highlight complexities underlying brain adaptations during the aging process, and support the notion that certain aspects of neurotransmission remain stable during the adult life span.

Importance of excitonic effect in charge separation at quantum-dot/organic interface: first-principles many-body calculations.

The staggered alignment of quasiparticle energy levels is widely regarded to be the key criterion necessary for electron-hole charge separation to occur at heterogeneous material interfaces. However, staggered energy levels at nanoscale interfaces, such as those between organic molecules and inorganic quantum dots, do not necessarily imply charge separation across the interface because the excitonic effect is often significant. Using quantum Monte Carlo calculations, we perform a detailed study of the role of the excitonic effects on charge separation across a representative set of interfaces between organic molecules and quantum dots. We find that the exciton binding energy of charge transfer excitons is significantly larger than would be estimated from a simple Coulombic analysis and, at these nanoscale interfaces, can be as significant as that of Frenkel excitons. This implies that charge transfer excitons can act as trap states and facilitate electron-hole recombination instead of charge separation. We conclude that in general, for nanoscale interfaces, high-fidelity quantum many-body calculations are essential for an accurate evaluation of the detailed energetic balance between localized and delocalized excitons and, thus, are crucial for the predictive treatment of interfacial charge separation processes.

Identification of the local sources of paramagnetic noise in superconducting qubit devices fabricated on α-Al2O3 substrates using density-functional calculations.

Effective methods for decoupling superconducting qubits (SQs) from parasitic environmental noise sources are critical for increasing their lifetime and phase fidelity. While considerable progress has been made in this area, the microscopic origin of noise remains largely unknown. In this work, first principles density functional theory calculations are employed to identify the microscopic origins of magnetic noise sources in SQs on an α-Al2O3 substrate. The results indicate that it is unlikely that the existence of intrinsic point defects and defect complexes in the substrate are responsible for low frequency noise in these systems. Rather, a comprehensive analysis of extrinsic defects shows that surface aluminum ions interacting with ambient molecules will form a bath of magnetic moments that can couple to the SQ paramagnetically. The microscopic origin of this magnetic noise source is discussed and strategies for ameliorating the effects of these magnetic defects are proposed.

Path-integral Monte Carlo simulation of the warm dense homogeneous electron gas.

We perform calculations of the 3D finite-temperature homogeneous electron gas in the warm-dense regime (r(s) ≡ (3/4πn)(1/3)a(0)(-1) = 1.0-40.0 and Θ ≡ T/T(F) = 0.0625-8.0) using restricted path-integral Monte Carlo simulations. Precise energies, pair correlation functions, and structure factors are obtained. For all densities, we find a significant discrepancy between the ground state parametrized local density approximation and our results around T(F). These results can be used as a benchmark for developing finite-temperature density functionals, as well as input for orbital-free density function theory formulations.

Sensitivity to ostracism is blunted in suicide attempters only when they report suicidal ideation.

BACKGROUND: Modified pain perception is at the core of many theories on suicide; however, studies on the relationship between pain perception and suicidal behavior (attempt) have produced contradictory results. In this experimental study, we investigated whether physical pain and social pain are concomitantly influenced by suicidal ideation (SI) and past suicidal behavior. METHODS: 155 inpatients with depression (90 with and 65 without past history of suicide attempt) were included. They underwent thermal stimulation of the skin to assess physical pain tolerance and played the Cyberball game to assess their sensitivity to ostracism (social pain). Participants self-assessed current SI through the specific item in the Beck Depression Inventory. RESULTS: Pain tolerance was not associated with history of suicide attempt, current SI, and their interaction. Social pain was associated with the interaction between history of suicide attempt and current SI. Social pain was decreased in suicide attempters, compared with non-attempters, only when they reported current SI. LIMITATIONS: Cyberball game may not be representative of everyday stress and ecological social context. CONCLUSIONS: Unlike what suggested by many theories, pain tolerance does not seem to be necessary to attempt suicide. Suicide attempters with current SI displayed blunted sensitivity to ostracism and could be less willing to restore social affiliation compared with non-attempters.

Mediation effect of anxious attachment on relationship between childhood trauma and suicidal ideation sensitive to psychological pain levels.

BACKGROUND: Childhood trauma (CT), depression, and psychological pain are known predictors of suicidal ideation. Recent literature additionally highlights the importance of the attachment system. METHODS: We aimed to predict suicidal ideation through CT, attachment, and psychological and social pain by using mediation models aiming to predict suicidal ideation through CT (predictor) and attachment (mediator). In the same models, we introduced psychological or social pain as a moderator of the relationship between attachment, CT, and suicidal ideation. We included 161 depressed patients and assessed depression, attachment, CT, suicidal ideation, psychological pain, and social pain. RESULTS: We found (1) a complete mediating effect of anxious attachment (a2b2 = 0.0035, CI95% = [0.0010; 0.0069]) on the relationship between CT on suicidal ideation, and (2) a significant complete conditional mediating effect of anxious attachment and psychological pain (index of moderated mediation VAS: 0.0014; CI95% = [0.0002; 0.0032]) but not social pain on the relationship between CT and suicidal ideation. Both models were controlled for history of suicidal attempt, depression severity, and sex. CONCLUSIONS: Our results suggest a developmental profile of suicidal ideation in mood disorder that is characterized by the presence of CT and insecure attachment, especially anxious attachment, that is sensitive to experiences of psychological pain. Nevertheless, we cannot conclude that avoidantly attached individuals do not present the same mechanism, as they may not disclose those ideas.

A Visual Interpretation Algorithm for Assessing Brain Tauopathy with 18F-MK-6240 PET.

In vivo characterization of pathologic deposition of tau protein in the human brain by PET imaging is a promising tool in drug development trials of Alzheimer disease (AD). 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (18F-MK-6240) is a radiotracer with high selectivity and subnanomolar affinity for neurofibrillary tangles that shows favorable nonspecific brain penetration and excellent kinetic properties. The purpose of the present investigation was to develop a visual assessment method that provides both an overall assessment of brain tauopathy and regional characterization of abnormal tau deposition. Methods: 18F-MK-6240 scans from 102 participants (including cognitively normal volunteers and patients with AD or other neurodegenerative disorders) were reviewed by an expert nuclear medicine physician masked to each participant's diagnosis to identify common patterns of brain uptake. This initial visual read method was field-tested in a separate, nonoverlapping cohort of 102 participants, with 2 additional naïve readers trained on the method. Visual read outcomes were compared with semiquantitative assessments using volume-of-interest SUV ratio. Results: For the visual read, the readers assessed 8 gray-matter regions per hemisphere as negative (no abnormal uptake) or positive (1%-25% of the region involved, 25%-75% involvement, or >75% involvement) and then characterized the tau binding pattern as positive or negative for evidence of tau and, if positive, whether brain uptake was in an AD pattern. The readers demonstrated agreement 94% of the time for overall positivity or negativity. Concordance on the determination of regional binary outcomes (negative or positive) showed agreement of 74.3% and a Fleiss κ of 0.912. Using clinical diagnosis as the ground truth, the readers demonstrated a sensitivity of 73%-79% and specificity of 91%-93%, with a combined reader-concordance sensitivity of 80% and specificity of 93%. The average SUV ratio in cortical regions showed a robust correlation with visually derived ratings of regional involvement (r = 0.73, P < 0.0001). Conclusion: We developed a visual read algorithm for 18F-MK-6240 PET offering determination of both scan positivity and the regional degree of cortical involvement. These cross-sectional results show strong interreader concordance on both binary and regional assessments of tau deposition, as well as good sensitivity and excellent specificity supporting use as a tool for clinical trials.

Preliminary Exploration of Pseudo-CT-Based Attenuation Correction for Simultaneous PET/MRI Brain Imaging in Nonhuman Primates.

This study aimed to develop a template-based attenuation correction (AC) for the nonhuman primate (NHP) brain. We evaluated the effects of AC on positron emission tomography (PET) data quantification with two experimental paradigms by comparing the quantitative outcomes obtained using a segmentation-based AC versus template-based AC. Population-based atlas was generated from ten adult rhesus macaques. Bolus experiments using [18F]PF-06455943 and a bolus-infusion experiment using [11C]OMAR were performed on a 3T Siemens PET/magnetic resonance-imaging (MRI). PET data were reconstructed with either µ map obtained from the segmentation-based AC or template-based AC. The standard uptake value (SUV), volume of distribution (VT), or percentage occupancy of rimonabant were calculated for [18F]PF-06455943 and [11C]OMAR PET, respectively. The leave-one-out cross-validation showed that the absolute percentage differences were 2.54 ± 2.86% for all region of interests. The segmentation-based AC had a lower SUV and VT (∼10%) of [18F]PF-06455943 than the template-based method. The estimated occupancy was higher in the template-based method compared to the segmentation-based AC in the bolus-infusion study. However, future studies may be needed if a different reference tissue is selected for data quantification. Our template-based AC approach was successfully developed and applied to the NHP brain. One limitation of this study was that validation was performed by comparing two different MR-based AC approaches without validating against AC methods based on computed tomography (CT).