A Framework to Control Functional Connectivity in the Human Brain

In this paper, we propose a framework to control brain-wide functional connectivity by selectively acting on the brain's structure and parameters. Functional connectivity, which measures the degree of correlation between neural activities in different brain regions, can be used to distinguish between healthy and certain diseased brain dynamics and, possibly, as a control parameter to restore healthy functions. In this work, we use a collection of interconnected Kuramoto oscillators to model oscillatory neural activity, and show that functional connectivity is essentially regulated by the degree of synchronization between different clusters of oscillators. Then, we propose a minimally invasive method to correct the oscillators' interconnections and frequencies to enforce arbitrary and stable synchronization patterns among the oscillators and, consequently, a desired pattern of functional connectivity. Additionally, we show that our synchronization-based framework is robust to parameter mismatches and numerical inaccuracies, and validate it using a realistic neurovascular model to simulate neural activity and functional connectivity in the human brain.Comment: To appear in the proceedings of the 58th IEEE Conference on Decision and Contro

Development and Role in Therapy of Canakinumab in Adult-Onset Still's Disease

Adult-onset Still's disease (AOSD) is a rare inflammatory disease of unknown etiology typically characterized by episodes of spiking fever, evanescent rash, arthralgia, leukocytosis, and hyperferritinemia. The pivotal role of interleukin (IL)-1 and other pro-inflammatory cytokines gives rise to the development of new targeted therapies. Currently, AOSD patients can benefit from efficient and well tolerated biologic agents, such as IL-1, IL-6, and tumour necrosis factor (TNF)-\u3b1 antagonists. Canakinumab, a human monoclonal anti-IL-1\u3b2 antibody, is indicated for the treatment of different autoinflammatory syndromes in adults, adolescents, and children and it has recently been approved for AOSD treatment. In this article, we summarize the structural and biochemical data describing the molecular interactions between Canakinumab and its target antigen. Some special considerations of the pharmacological properties of Canakinumab are included. We also review the safety, efficacy and tolerability of this drug for the treatment of AOSD

Decoding a Three-Dimensional Conformal Manifold

We study the one-dimensional complex conformal manifold that controls the infrared dynamics of a three-dimensional $\mathcal{N}=2$ supersymmetric theory of three chiral superfields with a cubic superpotential. Two special points on this conformal manifold are the well-known XYZ model and three decoupled copies of the critical Wess-Zumino model. The conformal manifold enjoys a discrete duality group isomorphic to $S_4$ and can be thought of as an orbifold of $\mathbf{CP}^1$. We use the $4-\varepsilon$ expansion and the numerical conformal bootstrap to calculate the spectrum of conformal dimensions of low-lying operators and their OPE coefficients, and find a very good quantitative agreement between the two approaches.Comment: 59 pages, 13 figure

OR14-1PATTERNS AND TRANSITIONS IN SUBSTANCE USE AMONG YOUNG SWISS MEN

Introduction. The stages of involvement in illicit drugs other than cannabis remain vague and few studies focused on the last steps of drug-use trajectories. This study investigated this topic. Methods. We used data from the Swiss Longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) to assess exposure to drug use (alcohol, tobacco, 16 illicit drugs including heroin, and five prescription drugs including opioids) at two times point (N = 5,041). Patterns and trajectories of drug use were studied using latent transition analysis (LTA) and cross-lagged panel models. Results. The LTA identified five classes of drug users showing a pattern involving adding alcohol, tobacco, cannabis, middle-stage drugs (uppers, hallucinogens, inhaled drugs), and final-stage drugs (e.g. heroin, ketamine, crystal meth). The most common transition was to remain in the same latent class. Heroin use predicted later opioid use (b = .071, p = .003) but not the reverse (b = -.005, p = .950). Conclusion. The pattern of drug use displayed the well-known sequence of drug involvement (licit drugs/cannabis/other illicit drugs), but added a distinction between "middle-stage" and "final-stage" drugs. Progression along the whole drug course remained rare among participants in their twenties. For the final stage, heroin appeared as to be a step for opioid us

Recreational Marijuana Laws and Junk Food Consumption: Evidence Using Border Analysis and Retail Sales Data

We use retail scanner data on purchases of high calorie food to study the link between recreational marijuana laws (RMLs) and consumption of high calorie food. To do this we exploit differences in the timing of introduction of marijuana laws among states and find that they are complements. Specifically, in counties located in RML states, monthly sales of high calorie food increased by 3.1 percent for ice cream, 4.1 for cookies, and 5.3 percent for chips. Results are robust to including placebo effective dates for RMLs in treated states as well as when using synthetic control methods as an alternative methodology

An 8-Item Short Form of the Inventory of Dimensions of Emerging Adulthood (IDEA) Among Young Swiss Men.

Emerging adulthood is a period of life transition, in which youths are no longer adolescents but have not yet reached full adulthood. Measuring emerging adulthood is crucial because of its association with psychopathology and risky behaviors such as substance use. Unfortunately, the only validated scale for such measurement has a long format (Inventory of Dimensions of Emerging Adulthood [IDEA]-31 items). This study aimed to test whether a shorter form yields satisfactory results without substantial loss of information among a sample of young Swiss men. Data from the longitudinal Cohort Study on Substance Use Risk Factors were used (N = 5,049). IDEA, adulthood markers (e.g., parenthood or financial independence), and risk factors (i.e., substance use and mental health issues) were assessed. The results showed that an 8-item, short-form scale (IDEA-8) with four factors (experimentation, negativity, identity exploration, and feeling in between) returned satisfactory results, including good psychometric properties, high convergence with the initial scale, and strong empirical validity. This study was a step toward downsizing a measure of emerging adulthood. Indeed, this 8-item short form is a good alternative to the 31-item long form and could be more convenient for surveys with constraints on questionnaire length. Moreover, it should help health care practitioners in identifying at-risk populations to prevent and treat risky behaviors

Subthreshold problem drinkers in DSM-5 alcohol use disorder classification.

The DSM-5 defined alcohol use disorder (AUD) to better cover undiagnosed subthreshold alcohol users, but few studies have investigated this topic. This study aimed to test whether subthreshold problem drinkers were a distinct subgroup of undiagnosed drinkers according to the DSM-5 AUD classification by investigating drinking patterns and longitudinal trajectories. Data were collected in the Cohort Study on Substance Use Risk Factors from young Swiss men in their early twenties (n = 4,630) at two time points. Participants responded to the 11 criteria of the DSM-5 AUD and to variables related to drinking patterns. Among drinkers, 23.2% and 23.5% of the participants were subthreshold problem drinkers at baseline and follow-up, respectively. The trends showed that 29.4% of them remained subthreshold problem drinkers over time. Those who remained subthreshold problem drinkers or progressed to AUD status were likely to meet the same criterion/add a new one. Subthreshold problem drinkers showed concurrent and later drinking patterns that were in between those of symptom-free drinkers and AUD drinkers. Subthreshold problem drinkers were an important subgroup of drinkers with risky drinking patterns, but they did not necessarily progress to later AUD status and did not appear to be a consistent subgroup over time. Subthreshold problem drinkers did not seem to be a subgroup of undiagnosed problem drinkers in the current DSM-5 classification. The results showed that AUD appeared to be a dimensional construct, in which one additional criterion was associated with worse alcohol-related outcomes. (Am J Addict 2016;25:408-415)

Trajectories of drug use among French young people : prototypical stages of involvement in illicit drug use

Aims: This study investigated patterns and trajectories of substance use, with a special focus on illicit drugs other than cannabis. It examined both patterns and trajectories of use among a general population-based sample. Methods: We used data from the 2011 French ESCAPAD survey of French 17-year-olds to assess exposure and age of initiation of 14 licit and illicit drugs (N=23,882). Latent class analysis (LCA) and survival analyses were performed. Results: The results of the LCA showed that patterns of illicit drug use clearly distinguished between two groups of other illicit drugs: 1) amphetamines/speed, cocaine, ecstasy/MDMA, magic mushrooms, poppers, and solvents; 2) crack/freebase, GHB/GBL, heroine, LSD, and ketamine. Survival analyses highlighted that trajectories involved the first group before the second one. Conclusions: Prototypical drug use patterns and trajectories should include a distinction between two groups of illicit drugs. Preventive actions should focus on young people in their early teens, since very young users are more likely to progress to illicit drug use, and further studies should include this distinction instead of aggregating other illicit drugs into a single category