Algorithm-Driven Substance Use Disorder Treatment for Inner-City Clients With Serious Mental Illness and Multiple Impairments.

ABSTRACT: Mental health clients with serious mental illness in urban settings experience multiple chronic stresses related to poverty, unemployment, discrimination, homelessness, incarceration, hospitalization, posttraumatic stress disorder, pain syndromes, traumatic brain injury, and other problems. Substance use disorder exacerbates these difficulties. This study examined the efficacy of algorithm-driven substance use disorder treatments for 305 inner-city mental health clients with multiple challenges. Researchers assessed substance use quarterly using a combination of standardized self-reports and case manager ratings. Of the 305 multiply impaired clients who began treatment, 200 (66%) completed 2 years of treatment. One fourth (n = 53) of the completers were responders who developed abstinence and improved community function; one half (n = 97) were partial responders, who reduced substance use but did not become abstinent; and one fourth (n = 50) were nonresponders. Evidence-based interventions for substance use disorder can be effective for multiply impaired, inner-city clients, but numerous complications may hinder recovery.

Novel Approaches To Kill Toxoplasma gondii by Exploiting the Uncontrolled Uptake of Unsaturated Fatty Acids and Vulnerability to Lipid Storage Inhibition of the Parasite.

Toxoplasma gondii, an obligate intracellular parasite replicating in mammalian cells within a parasitophorous vacuole (PV), is an avid scavenger of lipids retrieved from the host cell. Following lipid uptake, this parasite stores excess lipids in lipid droplets (LD). Here, we examined the lipid storage capacities of Toxoplasma upon supplementation of the culture medium with various fatty acids at physiological concentrations. Supplemental unsaturated fatty acids (oleate [OA], palmitoleate, linoleate) accumulate in large LD and impair parasite replication, whereas saturated fatty acids (palmitate, stearate) neither stimulate LD formation nor impact growth. Examination of parasite growth defects with 0.4 mM OA revealed massive lipid deposits outside LD, indicating enzymatic inadequacies for storing neutral lipids in LD in response to the copious salvage of OA. Toxoplasma exposure to 0.5 mM OA led to irreversible growth arrest and lipid-induced damage, confirming a major disconnect between fatty acid uptake and the parasite's cellular lipid requirements. The importance of neutral lipid synthesis and storage to avoid lipotoxicity was further highlighted by the selective vulnerability of Toxoplasma, both the proliferative and the encysted forms, to subtoxic concentrations of the acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) pharmacological inhibitor T863. T863-treated parasites did not form LD but instead built up large membranous structures within the cytoplasm, which suggests improper channeling and management of the excess lipid. Dual addition of OA and T863 to infected cells intensified the deterioration of the parasite. Overall, our data pinpoint Toxoplasma DGAT as a promising drug target for the treatment of toxoplasmosis that would not incur the risk of toxicity for mammalian cells.

Conversion table for running on lower body positive pressure treadmills.

Lower body positive pressure (LBPP) or antigravity treadmills are becoming increasingly popular in sports and rehabilitation settings. Running at a decreased body weight (BW) reduces metabolic cost, which can be offset by running at faster speeds. To date, however, little is known about how much faster someone must run to offset the reduced metabolic cost. This study aimed to develop a user-friendly conversion table showing the speeds required on an LBPP treadmill to match the equivalent metabolic output on a regular, non-LBPP, treadmill across a range of body weight supports. A total of 20 recreational runners (11 males, 9 females) ran multiple 3-minute intervals on a regular treadmill and then on an LBPP treadmill at 6 different BWs (50-100%, 10% increments). Metabolic outputs were recorded and matched between the regular and LBPP treadmill sessions. Using regression analyses, a conversion table was successfully created for the speeds from 6.4 to 16.1 km·h (4 to 10 mph) in 0.8 km·h (0.5 mph) increments on the regular treadmill and BW proportions of 50, 60, 70, 80, 90, and 100% on an LBPP treadmill. The table showed that a greater increase in speed on the LBPP treadmill was needed with more support (p < 0.001) but that the proportion increase was smaller at higher speeds (p < 0.001). This research has implications for coaches or practitioners using or prescribing training on an LBPP treadmill.

Oxygen consumption of elite distance runners on an anti-gravity treadmill®.

Lower body positive pressure (LBPP), or 'anti-gravity' treadmills® have become increasingly popular among elite distance runners. However, to date, few studies have assessed the effect of body weight support (BWS) on the metabolic cost of running among elite runners. This study evaluated how BWS influenced the relationship between velocity and metabolic cost among 6 elite male distance runners. Participants ran three- 16 minute tests consisting of 4 stages of 4 minutes at 8, 7, 6 and 5 min·mile(-1) pace (3.35, 3.84, 4.47 and 5.36 m·s(-1)), while maintaining an aerobic effort (Respiratory Exchange Ratio ≤1.00). One test was run on a regular treadmill, one on an anti-gravity treadmill with 40% BWS and one with 20% BWS being provided. Expired gas data were collected and regression equations used to determine and compare slopes. Significant decreases in oxygen uptake (V̇O2) were found with each increase in BWS (p < 0.001). At 20% BWS, the average decrease in net VO2 was greater than proportional (34%), while at 40% BWS, the average net reduction in VO2 was close to proportional (38%). Across velocities, the slope of the relationship between VO2 and velocity (ΔV̇O2/Δv) was steeper with less support. The slopes at both the 20% and 40% BWS conditions were similar, especially when compared to the regular treadmill. Variability in VO2 between athletes was much greater on the LBPP treadmill and was greater with increased levels of BWS. In this study we evaluated the effect of body weight support on V̇O2 among elite distance runners. We have shown that oxygen uptake decreased with support, but not in direct proportion to that support. Further, because of the high variability in oxygen uptake between athletes on the LBPP treadmill, prediction equations may not be reliable and other indicators (heart rate, perceived exertion or directly measured oxygen uptake) should be used to guide training intensity when training on the LBPP treadmill. Key pointsWith increasing amounts of body weight-support (BWS), the slope of the relationship between velocity and oxygen consumption (ΔVO2/Δv) decreases significantly. This means the change in oxygen consumption (VO2) is significantly smaller over a given change in velocity at higher amounts of BWS.There is a non-linear decrease in VO2 with increasing BWS. As such, with each increment in the amount of BWS provided, the reduction in VO2 becomes increasingly smaller.This paper provides first of its kind data on the effects of BWS on the cost of running among highly trained, elite runners. The outcomes of this study are in line with previous findings among non-elite runners.

Neural network for 3D inertial confinement fusion shell reconstruction from single radiographs.

In inertial confinement fusion (ICF), x-ray radiography is a critical diagnostic for measuring implosion dynamics, which contain rich three-dimensional (3D) information. Traditional methods for reconstructing 3D volumes from 2D radiographs, such as filtered backprojection, require radiographs from at least two different angles or lines of sight (LOS). In ICF experiments, the space for diagnostics is limited, and cameras that can operate on fast timescales are expensive to implement, limiting the number of projections that can be acquired. To improve the imaging quality as a result of this limitation, convolutional neural networks (CNNs) have recently been shown to be capable of producing 3D models from visible light images or medical x-ray images rendered by volumetric computed tomography. We propose a CNN to reconstruct 3D ICF spherical shells from single radiographs. We also examine the sensitivity of the 3D reconstruction to different illumination models using preprocessing techniques such as pseudo-flatfielding. To resolve the issue of the lack of 3D supervision, we show that training the CNN utilizing synthetic radiographs produced by known simulation methods allows for reconstruction of experimental data as long as the experimental data are similar to the synthetic data. We also show that the CNN allows for 3D reconstruction of shells that possess low mode asymmetries. Further comparisons of the 3D reconstructions with direct multiple LOS measurements are justified.

The failed repressor: EEG asymmetry as a moderator of the relation between defensiveness and depressive symptoms.

This study assessed the joint effects of defensiveness and frontal asymmetry in predicting symptoms of depression and anxiety. Depression symptoms were measured with the Beck Depression Inventory (BDI) and anxiety symptoms with the Taylor Manifest Anxiety Scale (TMAS). Defensiveness was assessed with both the Marlowe Crowne Social Desirability Scale (MCSD) and the Eysenck Personality Questionnaire L scale (EPQL). Participants completed two EEG recording sessions 3 weeks apart. Six baselines, three eyes open and three eyes closed, were recorded in each session. Alpha power (8-13 Hz) was computed and log transformed. R-L asymmetry was computed at eight pairs of homologous sites for aggregated data. Defensiveness (EPQL and MCSD scores) and depression symptoms (BDI) were assessed at the beginning of the first session. L and MCSD correlated positively with anterior R-L asymmetries. For both scales, the highest correlations were observed at F8-F7. L interacted with F8-F7 asymmetry to predict depressive symptoms. Among left frontally active individuals, there was trend toward a negative correlation between L and BDI. Among the right frontally active individuals, the correlation between L and the BDI was positive. MCSD did not moderate the relation between F8-F7 asymmetry and BDI. The results are consistent with the hypothesis that defensiveness protects against symptoms of depression in the context of left frontal activity, and serves as a diathesis for depression in the context of right frontal activity. High-defensive individuals who are right frontally active may represent "failed repressors," i.e. individuals for whom defensiveness does not protect against depression, and may even exacerbate it.

Interpersonal defensiveness and diminished perceptual acuity for the odor of a putative pheromone: androstenone.

This study assessed the relationship of repressive coping and defensiveness to the perception of androstenone, which is a putative human pheromone with relevance to social perception. In Experiment 1, 34 men and 34 women between the ages of 16-28 sniffed pairs of bottles containing silicone (the solvent control) paired with either isoamyl acetate (IAA) or androstenone in an eight trial, two-alternative forced-choice task. Participants chose which hand they believed the odor was in, and rated the odor's intensity and their confidence in their response on a 0-10 scale. Defensiveness was measured with the Eysenck Personality Questionnaire (EPQ) L scale. As predicted, defensiveness was associated with decreased perception of androstenone, but not IAA. Decreased detection accuracies, confidence, and intensity ratings for androstenone were associated with high defensiveness. The effect was stronger among women. None of the IAA detection variables correlated with the L scale for either women or men. In Experiment 2, 22 women and 18 men between the ages of 18 and 27 were given 4 concentrations of IAA ranging from subthreshold to suprathreshold, and a blank-blank control. Detection accuracies, confidence ratings, and intensity ratings for IAA were not related to defensiveness for any of the concentrations, for either men or for women. The results are discussed in terms of motives to seek social approval and avoid social disapproval as they may relate to diminished awareness of androstenone.

Anterior EEG asymmetries and opponent process theory.

The opponent process theory of emotion [Solomon, R.L., and Corbit, J.D. (1974). An opponent-process theory of motivation: I. Temporal dynamics of affect. Psychological Review, 81, 119-143.] predicts a temporary reversal of emotional valence during the recovery from emotional stimulation. We hypothesized that this affective contrast would be apparent in asymmetrical activity patterns in the frontal lobes, and would be more apparent for left frontally active individuals. The present study tested this prediction by examining EEG asymmetries during and after blocked presentations of aversive pictures selected from the International Affective Picture System (IAPS). 12 neutral images, 12 aversive images, and 24 neutral images were presented in blocks. Participants who were right frontally active at baseline did not show changes in EEG asymmetry while viewing aversive slides or after cessation. Participants left frontally active at baseline, however, exhibited greater relative left frontal activity after aversive stimulation than before stimulation. Asymmetrical activity patterns in the frontal lobes may relate to affect regulatory processes, including contrasting opponent after-reactions to aversive stimuli.

Can EEG asymmetry patterns predict future development of anxiety and depression? A preliminary study.

Previous research has shown that those reporting symptoms of depression and anxiety tend to exhibit greater relative right frontal electroencephalographic (EEG) activity. Thus, Davidson [Davidson, R.J., 1995. Cerebral asymmetry, emotion, and affective style. In: Davidson, R.J., Hugdahl, K. (Eds.), Brain Asymmetry. MIT, Cambridge, pp. 361-387] has suggested that greater relative right anterior activity may act as a vulnerability marker for the development of depression and anxiety disorders. This study therefore examined whether anterior and posterior EEG asymmetry patterns predicted anxiety and depressive symptoms one year later. At time 1, participants completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) and had baseline EEG activity recorded. Participants then completed the BDI and STAI one year later. Those with relatively greater EEG activity in the right anterior region reported greater trait anxiety one year later. These preliminary results suggest that relative right frontal EEG activity may predict future development of anxiety symptoms.

Personality correlates of startle habituation.

This study investigated the relationship between extraversion and rates of acoustic startle habituation, a potential biological marker for individual differences. Personality was measured using the Eysenck Personality Questionnaire (EPQ), the Sensation Seeking Scale (SSS), and Tellegen's Multidimensional Personality Questionnaire (MPQ). Higher EPQ Extraversion and higher SSS scores were associated with faster, more rapid startle habituation. Moreover, the relationship between extraversion and faster startle habituation was replicated in a second, follow-up sample. Within the initial study sample, lower scores on the Constraint (CON) factor of the MPQ (reflecting greater impulsiveness, risk-taking, and nonconformity) were also associated with faster startle habituation. Follow-up analyses revealed relationships between EPQ Extraversion, SSS, and low MPQ CON. These results suggest that faster habituation within the CNS may be associated tendencies toward impulsivity and behavioral disinhibition.

Heart rate, heart rate variability, and heartbeat detection with the method of constant stimuli: slow and steady wins the race.

The literature on heartbeat detection is fraught with disagreement about appropriate methods. Some laboratories advocate the heartbeat counting method, whereas others advocate the method of constant (MCS) stimuli task. Advocates of the MCS task argue that the heartbeat counting task is confounded by expectancies of heart rate, whereas the MCS task has the virtue of assessing individual heartbeat sensations. In this paper, we present preliminary evidence that heart rate information may also influence performance on the MCS task. Heartbeat detection was predicted by decreased heart rate variability and decreased heart rate. The results suggest that the temporal patterning of heartbeats may influence performance on the MCS task.

Relative left-frontal activity is associated with increased depression in high reassurance-seekers.

Excessive reassurance-seeking, which has been associated with depression in many studies, can be defined as the relatively stable tendency to seek assurance perseveratively from others. We hypothesized that although depression has been associated with left-frontal EEG hypoactivity, reassurance-seekers may possess a unique diathesis that is more likely to be associated with increased left-frontal activity. Data were collected from 12 volunteers who were receiving therapeutic services from a University Clinic. EEG asymmetry scores were averaged over two measurement occasions at least 3 weeks apart. As predicted, stable relative right-frontal activity was associated with increased depression in those who were low on reassurance-seeking, while stable relative left-frontal activity was associated with increased depression among high reassurance-seekers. Perhaps those who seek reassurance excessively do so because of their inability to alter their behavior even when environmental cues are no longer reinforcing, which can maintain or exacerbate their depressive symptoms.

NIF unconverted light and its influence on DANTE measurements.

NIF laser facility produces 1053 nm light and a fundamental requirement for NIF is to give up to 1.8 MJ of 351 nm light for target physics experiments. The 351 nm light is provided by frequency tripling the 1053 nm light in nonlinear crystals in the final optics assembly, just before the laser light enters the target chamber. Since this tripling process is not 100% efficient, unconverted light from the conversion process also enters the chamber. This unconverted light does not directly hit the target but it can strike target support structures at average intensities of few TW/cm2 where it can generate unwanted, background soft x-rays that are measured by the soft x-ray diagnostic DANTE installed on the NIF target chamber. This diagnostic quantifies the x-radiation intensity inside the hohlraum by measuring the x-ray flux coming from the target's laser entrance hole. Due to its centimeter wide field of view, it integrates x-ray emission from both the flux exiting a hohlraum laser entrance hole and from the target support structure irradiated by residual 1omega and 2omega unconverted light. This work gives quantitative evaluations of the unconverted light for the first time and the effects on DANTE measurements for the future NIF tuning experiment called "Shock timing." Emission spectra are significantly modified leading to an overestimation of radiative temperature during the foot of the laser pulse since background x-rays are predominant in first two DANTE channel measurements. Mitigations of these effects by coating silicon paddle with plastic, using a smaller collimator to reduce DANTE field of view or eliminating DANTE channels in the analysis have been investigated.