Objective: The development and deployment of technology-based assessments of clinical symptoms are increasing. This study used ecological momentary assessment (EMA) to examine clinical symptoms and relates these sampling results to structured clinical ratings. Methods: Three times a day for 30 days, participants with bipolar disorder (n=71; BPI) or schizophrenia (n=102; SCZ) completed surveys assessing five psychosis-related and five mood symptoms, in addition to reporting their location and who they were with at the time of survey completion. Participants also completed Positive and Negative Syndrome Scale (PANSS) interviews with trained raters. Mixed-model repeated-measures (MMRM) analyses examined diagnostic effects and the convergence between clinical ratings and EMA sampling. Results: In total, 12,406 EMA samples were collected, with 80-percent adherence to prompts. EMA-reported psychotic symptoms manifested substantial convergence with equivalent endpoint PANSS items. Patients with SCZ had more severe PANSS and EMA psychotic symptoms. There were no changes in symptom severity scores as a function of the number of previous assessments. Conclusions: EMA surveyed clinical symptoms converged substantially with commonly used clinical rating scales in a large sample, with high adherence. This suggested that remote assessment of clinical symptoms is valid and practical and was not associated with alterations in symptoms as a function of reassessment, with additional benefits of in the moment sampling, such as eliminating recall bias and the need for informant reports.

OBJECTIVES: Disability is common in bipolar disorder (BD) and predicted by persistent sadness. We used ecological momentary assessment (EMA) to examine daily activities in people with BD and schizophrenia. We classified activities as productive, unproductive, or passive recreation, relating them to momentary sadness, location, and social context. METHODS: 71 people with BD and 102 people with schizophrenia were sampled 3 times/day for 30 days with an EMA survey. Each survey asked where they were, with whom, what they were doing, and if they were sad. RESULTS: People with BD were home more than 50% of the time. There were no differences in prevalence of activity types across diagnoses. People with BD were less likely to report only one activity since the prior survey, but the most surveys still reported only one. For both groups, sadness and being home and alone since the last survey was associated with less productive activity and more passive recreation. CONCLUSIONS: Participants with BD and schizophrenia manifested high levels of unproductive and passive activities, predicted by momentary sadness. These activity patterns are consistent with descriptions of avolition and they minimally differentiated people with BD and schizophrenia. Previous reports of negative symptoms in BD may have been identifying these behaviors.

Background

Exercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation.

Methods

Rats were trained in the intravenous self-administration (IVSA) of D-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ∼ 22 h of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design.

Results

Provision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual's decrease in drug intake.

Conclusions

Wheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern.

Ensembles of distributed, heterogeneous resources, or Computational Grids, have emerged as popular platforms for large-scale scientific applications. This paper presents the Virtual Instrument project which targets those platforms. More specifically, the project seeks to provide an integrated application execution environment that enables end-users to run and interact with running scientific simulations on the Grid. This work is performed in the specific context of a computational biology application: MCell. Even though MCell provides the basis for running simulations, its capabilities are currently limited in terms of scale, ease-of-use, and interactivity. Those limitations preclude usage scenarios that are critical for scientific advances. Our goal is to create a scientific ``Virtual Instrument'' from MCell by allowing its users to transparently access Grid resources while being able to steer running simulations. In this paper, we motivate the need for an MCell Virtual Instrument. We then introduce a scheduling strategy that exploits the structure of MCell simulations and uses task priorities to accommodates computational steering. Finally, we describe our innovations and contributions in terms of Grid software design and development.

Pre-2018 CSE ID: CS2002-0707

BACKGROUND: Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans. OBJECTIVE: To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses. METHODS: Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSLs FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures. RESULTS: A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures. CONCLUSION: Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstems role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders.

INTRODUCTION: Performance-based assessments of social skills have detected impairments in people with severe mental illness and are correlated with functional outcomes in people with schizophrenia and bipolar disorder. The most common of these assessments, the Social Skills Performance Assessment (SSPA), has two communication scenarios and items measuring both social competence and appropriateness. As real-world competence and appropriateness appear to have different correlates, we hypothesized that SSPA Items measuring competence and appropriateness would be distinct and have different correlations with other outcomes. METHODS: We aggregated data from 557 people with schizophrenia, 106 with bipolar disorder, and 378 well controls from 4 separate research studies. All participants were assessed with both SSPA scenarios and other performance based and clinician-rated measures. A single expert rated the SSPA interactions for competence and appropriateness while blind to participant diagnoses. RESULTS: Participants with bipolar disorder and schizophrenia performed more poorly on every item of the SSPA than healthy controls. Items measuring social competence and appropriateness in communication were intercorrelated across scenarios, as were elements of socially competent communication, although the items measuring competence did not correlate substantially with appropriateness. Items assessing social competence, but not social appropriateness, correlated with better cognitive and functional performance and residential and financial independence. DISCUSSION: Social competence and social appropriateness were distinct elements of performance-based social skills with potential differences in their functional correlates. As both social competence and appropriateness impact functional outcomes, improvement in the measurement and treatment of appropriate communication seems to be an important goal.

Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients. Continuous CTLA4-Ig treatment was unexpectedly efficacious at inhibiting endogenous graft-reactive T cell expansion but was unable to inhibit late CD4+ and CD8+ T cell infiltration into the allografts, and rejection was observed in 50% of recipients by day 35 after transplantation. When CTLA4-Ig was combined with the sphingosine 1-phosphate receptor-1 (S1PR1) functional antagonist FTY720, alloantibody production was inhibited and donor-specific IFN-γ-producing T cells were reduced to levels approaching nonsensitized tolerant recipients. Late T cell recruitment into the graft was also restrained, and graft survival improved with this combination therapy. These observations suggest that a rational strategy consisting of inhibiting memory T cell expansion and trafficking into the allograft with CTLA4-Ig and FTY720 can promote allograft survival in allosensitized recipients.

Background

Intensive treatment programmes (ITPs) have shown promise for reducing PTSD and depression symptoms. It is still unknown whether treatment gains are maintained following completion.

Objective

This study examined whether veterans were able to maintain treatment gains for up to 12 months after an ITP for PTSD and whether reductions in negative posttrauma cognitions predicted treatment gain maintenance.

Methods

209 veterans (62.7% male, mean age = 40.86 years) completed a 3-week, CPT-based ITP for PTSD. Participants' PTSD (PCL-5) and depression (PHQ-9) symptoms were assessed at pre-treatment, post-treatment, and at 3-, 6-, and 12-month follow-up timepoints.

Results

Despite small symptom increases from post-treatment to 3-month follow-up, significant and clinically meaningful reductions in PTSD and depression symptoms were reported from intake to 12 months follow-up (averaging >18 points on the PCL-5 and >6 points on the PHQ-9; d = 1.28, and d = 1.18, respectively). Greater reductions in negative posttrauma cognitions during treatment were associated with lower PTSD (p <.001) and depression (p =.005) severity at follow-up. Most veterans who completed the aftercare survey followed treatment recommendations and reported seeing a mental health provider at 3-, 6-, and 12-months post-treatment. Aftercare treatment did not significantly predict whether veterans maintained treatment gains at follow-up.

Conclusions

Overall maintenance of treatment gains long-term suggests veterans may be able to apply skills acquired during the ITP following treatment. These findings further support the feasibility and effectiveness of intensive, trauma-focused, evidence-based therapy delivery.

By definition, adhesion/growth-regulatory galectins are known for their ability to bind β-galactosides such as Galβ(1 → 4)Glc (lactose). Indications for affinity of human galectin-1 to α-linked digalactosides pose questions on the interaction profile with such bound ligands and selection of the galactose moiety for CH-π stacking. These issues are resolved by a combination of (15)N-(1)H heteronuclear single quantum coherence (HSQC) chemical shift and saturation transfer difference nuclear magnetic resonance (STD NMR) epitope mappings with docking analysis, using the α(1 → 3/4)-linked digalactosides and also Galα(1 → 6)Glc (melibiose) as test compounds. The experimental part revealed interaction with the canonical lectin site, and this preferentially via the non-reducing-end galactose moiety. Low-energy conformers appear to be selected without notable distortion, as shown by molecular dynamics simulations. With the α(1 → 4) disaccharide, however, the typical CH-π interaction is significantly diminished, yet binding appears to be partially compensated for by hydrogen bonding. Overall, these findings reveal that the type of α-linkage in digalactosides has an impact on maintaining CH-π interactions and the pattern of hydrogen bonding, explaining preference for the α(1 → 3) linkage. Thus, this lectin is able to accommodate both α- and β-linked galactosides at the same site, with major contacts to the non-reducing-end sugar unit.

Visible disruptions of appropriate food distribution for end consumers during the onset of the COVID-19 pandemic prompted calls for an urgent, renewed look at how the U.S. agri-food system is impacted by and responds to pandemics, natural disasters, and human-made crises. Previous studies suggest the COVID-19 pandemic yielded uneven impacts across agri-food supply chain segments and regions. For a rigorously comparable assessment of the impact of COVID-19 on agri-food businesses, a survey was administered from February to April 2021 to five segments of the agri-food supply chain in three study regions (California, Florida, and the two-state region of Minnesota-Wisconsin). Results (N = 870) measuring the self-reported changes in quarterly business revenue in 2020 compared to businesses' typical experience pre-COVID-19 suggest significant differences across supply chain segments and regions. In the Minnesota-Wisconsin region, restaurants took the largest hit and the upstream supply chains were relatively unaffected. In California, however, the negative impacts were felt throughout the supply chain. Two factors likely contributed to regional differences: (1) regional disparities in pandemic evolution and governance and (2) structural differences in regional agri-food systems. Regionalized and localized planning and the development of best-practices will be necessary for the U.S. agri-food system to enhance preparedness for and resilience to future pandemics, natural disasters, and human-made crises.