Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial

BACKGROUND Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders. METHODS Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response. RESULTS Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms. LIMITATIONS This was a pilot feasibility and acceptability trial; results should be interpreted with caution. CONCLUSIONS Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety.This work was supported by a Postdoctoral National Research Service Award from the National Institutes of Health [F32 MH098490] to K. Ellard. (F32 MH098490 - Postdoctoral National Research Service Award from the National Institutes of Health)Accepted manuscrip

Neural correlates of emotion acceptance vs worry or suppression in generalized anxiety disorder

Recent emotion dysregulationmodels of generalized anxiety disorder (GAD) propose chronic worry in GAD functions as a maladaptive attempt to regulate anxiety related to uncertain or unpredictable outcomes. Emotion acceptance is an adaptive emotion regulation strategy increasingly incorporated into newer cognitive behavioral therapy (CBT) approaches to GAD to counter chronic worry. The current study explores themechanisms of emotion acceptance as an alternate emotion regulation strategy to worry or emotion suppression using functionalmagnetic resonance imaging. Twenty-one female participants diagnosed with GAD followed counterbalanced instructions to regulate responses to personally relevant worry statements by engaging in either emotion acceptance, worry or emotion suppression. Emotion acceptance resulted in lower ratings of distress than worry and was associated with increased dorsal anterior cingulate cortex (dACC) activation and increased ventrolateral prefrontal cortex (VLPFC)-amygdala functional connectivity. In contrast, worry showed significantly greater distress ratings than acceptance or suppression and was associated with increased precuneus, VLPFC, amygdala and hippocampal activation. Suppression did not significantly differ fromacceptance in distress ratings or amygdala recruitment, but resulted in significantly greater insula and VLPFC activation and decreased VLPFC-amygdala functional connectivity. Emotion acceptance closely aligned with activation and connectivity patterns reported in studies of contextual extinction learning and mindful awareness.National Institute of Mental Health (U.S.) (Grant F31 MH084422

Disorder Induced Stripes in d-Wave Superconductors

Stripe phases are observed experimentally in several copper-based high-Tc superconductors near 1/8 hole doping. However, the specific characteristics may vary depending on the degree of dopant disorder and the presence or absence of a low- temperature tetragonal phase. On the basis of a Hartree-Fock decoupling scheme for the t-J model we discuss the diverse behavior of stripe phases. In particular the effect of inhomogeneities is investigated in two distinctly different parameter regimes which are characterized by the strength of the interaction. We observe that small concen- trations of impurities or vortices pin the unidirectional density waves, and dopant disorder is capable to stabilize a stripe phase in parameter regimes where homogeneous phases are typically favored in clean systems. The momentum-space results exhibit universal features for all coexisting density-wave solutions, nearly unchanged even in strongly disordered systems. These coexisting solutions feature generically a full energy gap and a particle-hole asymmetry in the density of states.Comment: 28 pages, 8 figure

Timescales of spike-train correlation for neural oscillators with common drive

We examine the effect of the phase-resetting curve (PRC) on the transfer of correlated input signals into correlated output spikes in a class of neural models receiving noisy, super-threshold stimulation. We use linear response theory to approximate the spike correlation coefficient in terms of moments of the associated exit time problem, and contrast the results for Type I vs. Type II models and across the different timescales over which spike correlations can be assessed. We find that, on long timescales, Type I oscillators transfer correlations much more efficiently than Type II oscillators. On short timescales this trend reverses, with the relative efficiency switching at a timescale that depends on the mean and standard deviation of input currents. This switch occurs over timescales that could be exploited by downstream circuits

Estimation of quantitative genetic and stability parameters in maize under high and low N levels

AB It is important to breed maize (Zea mays L) cultivars with high performance under variable N levels. We studied the effect of N levels and estimated quantitative genetic parameters for grain yield, quality, and other traits, and examined stability of performance for grain yield in diverse Chinese maize germplasm. From 2006 to 2008, each year 20 and in total 30 maize hybrids, including commercial hybrids currently grown in this region and other ex¬perimental hybrids as well as high-oil hybrids, were tested using nine environments (location-year combinations) in North China Plain. In each environment, two replicated trials were grown: one under high N application rate (HN, 225 kg N ha-1) and the other under low N application rate (LN, no N fertilization). Compared to HN, grain yield was significantly reduced (35.6%) under LN level, as well as kernel number per ear, 1000-kernel weight, plant and ear heights, and protein concentration. In the analysis over environments under each N level, genotypic variance was significant and heritability was high for all traits. In the analyses across N levels and environments, genotypic variance was significant for all traits and larger than the genotype × N and/or environment interaction variance components except for protein concentration. In stability analyses across N levels, hybrids differed for their linear response to environments, and some showed dissimilar response under HN and LN levels. Our results indicated that breeding maize adapted to variable N levels is feasible with the Chinese germplasm available in the summer breeding programs in North China Plain. Multi-environment tests are required to identify hybrids with high grain yield under variable N conditions, and examining yield stability separately under HN and LN would be useful

The Anatomy of the Facial Vein: Implications for Plastic, Reconstructive, and Aesthetic Procedures

Background: Anatomical knowledge of the facial vasculature is crucial for successful plastic, reconstructive, and minimally invasive procedures of the face. Whereas the majority of previous investigations focused on facial arteries, the precise course, variability, and relationship with adjacent structures of the facial vein have been widely neglected. Methods: Seventy-two fresh frozen human cephalic cadavers (32 male and 40 female cadavers;mean age, 75.2 +/- 10.9 years;mean body mass index, 24.2 +/- 6.6 kg/m(2);99 percent Caucasian ethnicity) were investigated by means of layer-by-layer anatomical dissection. In addition, 10 cephalic specimens were investigated using contrast agent-enhanced computed tomographic imaging. Results: The facial vein displayed a constant course in relation to the adjacent anatomical structures. The vein was identified posterior to the facial artery, anterior to the parotid duct, and deep to the zygomaticus major muscle. The angular vein formed the lateral boundary of the deep medial cheek fat and the premaxillary space, and the medial boundary of the deep lateral cheek fat and the suborbicularis oculi fat. The mean distance of the inferior and superior labial veins, of the deep facial vein, and of the angular vein from the inferior orbital margin was 51.6 +/- 3.1, 42.6 +/- 2.3, 27.4 +/- 3.0, and 4.2 +/- 0.7 mm, respectively. Conclusions: This work provides detailed information on the course of the facial vein in relation to neighboring structures. The presented clinically relevant anatomical observations and descriptions of landmarks will serve as helpful information for plastic, reconstructive, and aesthetic surgeons

Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients

$\textbf {Background:}$ The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0–F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). $\textbf {Methods:}$ MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including $\it n$ = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80% sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV ) was performed. $\textbf {Results:}$ MFAP4 levels were shown to differ between no to moderate fibrosis stages F0–F2 and severe stages (F3 and F4) with high statistical significance ($\it t$ test on log scale, $\it p$ value $<2.2·10^{-16}$). In the LOOCV, the univariate classification resulted in 85.8% sensitivity and 54.9% specificity while the multivariate model yielded 81.3% sensitivity and 61.5% specificity (restricted approaches). $\textbf {Conclusions:}$ We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals

Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

Abstract Background Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. Methods We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. Results and conclusions We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Patterns of cooperation: fairness and coordination in networks of interacting agents

We study the self-assembly of a complex network of collaborations among self-interested agents. The agents can maintain different levels of cooperation with different partners. Further, they continuously, selectively, and independently adapt the amount of resources allocated to each of their collaborations in order to maximize the obtained payoff. We show analytically that the system approaches a state in which the agents make identical investments, and links produce identical benefits. Despite this high degree of social coordination some agents manage to secure privileged topological positions in the network enabling them to extract high payoffs. Our analytical investigations provide a rationale for the emergence of unidirectional non-reciprocal collaborations and different responses to the withdrawal of a partner from an interaction that have been reported in the psychological literature.Comment: 20 pages, 8 figure