Biased Attentional Processing for Negative Emotion and Youth Internalizing Psychopathology: The Role of Attentional Control Deficits

Biased attention for salient negative emotional stimuli is a proposed cognitive mechanism of internalizing disorders, namely depression and anxiety. Previous studies have demonstrated biases in bottom-up, stimulus-driven attentional systems, as well as top-down, goal-oriented attentional systems, in the context of negative emotion. However, the underlying cognitive mechanisms that drive these biases, such as attentional control deficits, are not well understood. Furthermore, given the high degree of conceptual and empirical overlap between depression and anxiety, it is unclear how biased attention might relate to constructs common across both disorders, such as general distress, versus what is specific to each disorder. The current study utilized an emotional adaptation of the Antisaccade Task with eye-tracking to precisely and accurately tease apart components of attentional control, including inhibition and shifting, in the context of social threat (i.e., anger) in a community sample of youth and young adults (ages 13-22; N = 80). Findings show that difficulty inhibiting attention for social threat is associated with symptoms of general distress, which are shared across depression and anxiety, as well as symptoms of physiological hyperarousal that are specific to anxiety. Overall, findings further clarify what specific components of attentional control deficits underlie biased attentional processing, a well-established cognitive mechanism of internalizing disorders

One-Year Follow-Up of a Randomized Controlled Trial Piloting a Mindfulness-Based Group Intervention for Adolescent Insulin Resistance

IntroductionTo explore if a brief mindfulness-based intervention (MBI) leads to sustained, improved clinical outcomes in adolescents at-risk for type 2 diabetes (T2D).MethodsParticipants were 12–17y girls with overweight/obesity, elevated depression symptoms, and T2D family history participating in a randomized, controlled pilot trial of a six-session MBI vs. cognitive-behavioral therapy (CBT) group. At baseline and 1-year, mindfulness, depression, insulin resistance (IR), and body composition were assessed with validated instruments.ResultsOne-year retention was 71% (n = 12) in MBI; 81% (n = 13) in CBT. At 1-year, depression decreased (Cohen’s d = 0.68) and IR decreased (d = 0.73) in adolescents randomized to MBI compared to those in CBT. There were no significant between-condition differences in mindfulness, adiposity, or BMI.DiscussionOne-year outcomes from this randomized, controlled pilot trial suggest that brief MBI may reduce depression and IR in at-risk adolescents. Replication and exploration of mechanisms within the context of a larger clinical trial are necessary.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02218138

Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences with Age and between Healthy Donors and Cancer Patients not Detected in Analysis of Standard Immune Cell Types

Recent advances in human immunology have led to the identification of novel immune cell subsets and the biological function of many of these subsets has now been identified. The recent US Food and Drug Administration approval of several immunotherapeutics for the treatment of a variety of cancer types and the results of ongoing immunotherapy clinical studies requires a more thorough interrogation of the immune system. We report here the use of flow cytometry-based analyses to identify 123 immune cell subsets of peripheral blood mononuclear cells. The use of these panels defines multiple differences in younger (< 40 years) vs. older (≥ 40 years) individuals and between aged-matched apparently healthy individuals and metastatic cancer patients, aspects not seen in the analysis of the following standard immune cell types: CD8, CD4, natural killer, natural killer-T, regulatory T, myeloid derived suppressor cells, conventional dendritic cells (DCs), plasmacytoid DCs and B cells. The use of these panels identifying 123 immune cell subsets may aid in the identification of patients who may benefit from immunotherapy, either prior to therapy or early in the immunotherapeutic regimen, for the treatment of cancer or other chronic or infectious diseases

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Laboring with Love: The Spirituality of Birth from a Doula’s Perspective

Exploring the spiritual aspects of birth through conversations with practicing doulas in the Western Carolina

Motor Unit Characteristics and Proprioceptive Deficits of the Upper Limb in Patients with Type II Diabetes

Persons with Type II Diabetes (pwT2D) are at risk of developing nerve disorders that result in sensorimotor dysfunction, particularly of the hands and feet. Neuromuscular and proprioceptive dysfunction associated with diabetes are two areas needing more research to determine their contribution to T2D related functional impairments. Most work in these two areas has been focused on deficits in the lower limb. Proprioceptive dysfunction in the upper limb associated with T2D has yet to be characterized. Similarly, evaluation of neuromuscular dysfunction in the upper limb is lacking. Knowing that peripheral neuropathy (PN) affects the hands in addition to the feet and legs, this is an area that should be explored. Thus, the purpose of this study is to examine the neuromuscular and proprioceptive effects on the upper limb in pwT2D. This will be achieved by a) evaluating the effects of T2D on kinematic performance of a reach-to-pinch task; b) characterizing T2D associated motor unit properties in five upper limb muscles; and c) determine if observed alterations to motor unit characteristics are length-dependent in the upper limb. Three groups were recruited: young, healthy controls (group 1, 18-30 years old), T2D group (group 2, 60+ years old with established T2D), and an age- and sex-matched Control group without T2D (group 3, 60+ years old without a history of diabetes). Group 1 underwent sensory evaluation (tactile and vibrotactile sensation) and neuromuscular evaluation (nerve stimulation and motor evaluation) and served as an approach validation. Groups 2 and 3 underwent blood sugar and cholesterol testing, sensory evaluation (tactile and vibrotactile sensation), neuromuscular evaluation (nerve stimulation and motor evaluation), and proprioceptive evaluation (reach-to-pinch task). Overall, sensory thresholds did not differ between T2D and Control participants. CMAP amplitude and MUNIX were significantly reduced in Control participants compared to pwT2D. Additionally, mean pinch location error was significantly worse for pwT2D in addition to differences in wrist extension/flexion (ex/fl), wrist abduction/adduction (ab/ad), CMC1 ab/ad, MCP2 ex/fl, and MCP2 ab/ad angular joint trajectories and index finger and hand transport trajectories between the two groups. These findings suggest proprioception of the upper extremity is altered in pwT2D and they exhibit a unique aperture position and aiming strategy during a reach-to-pinch task. These findings help to understand proprioceptive and neuromuscular function of the upper limb in pwT2D, with implications to early identify patients who may need medical and/or lifestyle intervention.Health and Human Performance, Department o

Associations among Negative Parenting, Attention Bias to Anger, and Social Anxiety among Youth

Theories of affective learning suggest that early experiences contribute to emotional disorders by influencing the development of processing biases for negative emotional stimuli. Although studies show that physically abused children preferentially attend to angry faces, it is unclear whether youth exposed to more typical aspects of negative parenting would exhibit the same type of bias. The current studies extend previous research by linking observed negative parenting styles (e.g. authoritarian) and behaviors (e.g. criticism and negative affect) to attention bias for angry faces in both a psychiatrically enriched (ages 11–17 years; N = 60) and a general community (ages 9–15 years; N = 75) sample of youth. In addition, the association between observed negative parenting (e.g. authoritarian style and negative affect) and youth social anxiety was mediated by attention bias for angry faces in the general community sample. Overall, findings provide preliminary support for theories of affective learning and risk for psychopathology among youth

Improved Method for Simulating Groundwater Inundation Using the MODFLOW 6 Lake Transport Package

Groundwater inundation due to sea level rise can affect island and coastal freshwater resources by exposing water tables to direct, continuous evaporation. Numerical simulations of groundwater inundation effects on coastal and island aquifers have been limited by an inability to simulate solute transport and variable density flow between the aquifer and lakes formed by groundwater inundation. Consequently, we contributed to the development of a new tool, the Lake Transport Package, for MODFLOW 6 that can calculate solute concentrations within lakes and allows for variable density flow between lakes and aquifers. Here we use groundwater inundation as an example application to showcase the functionality of the Lake Transport Package and the advantages of using this tool over past methods of representing groundwater inundation. We developed hypothetical island simulations based on hydrogeological characteristics of the Bahamas. Multiple sea level rise and lake evaporation rates were simulated to evaluate the effects of groundwater inundation on freshwater lens size for different climates. The results demonstrate the ability of the Lake Transport Package to calculate the solute concentration of the lake for transient simulations, including hypersaline concentrations. Higher sea level rise and greater lake evaporation rates lead to a greater loss of the freshwater lens and higher lake salinity. The formation of a lake and corresponding expansion due to groundwater inundation increases the loss of freshwater by 6–36%, depending on the lake evaporation rate. These simulations validate the performance and demonstrate usefulness of the Lake Transport Package as a tool in representing groundwater inundation