The Use of Structured Imagery and Dispositional Measurement to Assess Situational Use of Mindfulness Skills

The recent proliferation of studies on mindfulness produced varying theoretical models, each based in part on how mindfulness is assessed. These models agree, however, that mindfulness encompasses moment-to-moment or situational experiences. Incongruence between dispositional and situational assessment would be problematic for theory and empirical research. In particular, it remains to be established whether situational measurement is an accurate method for mindfulness assessment and whether dispositional measures are able to accurately detect mindfulness skills in various situations. The association between dispositional and situational mindfulness processes (i.e., situational attention awareness and emotion acceptance) was examined in two studies. In Study 1 (N = 148), independent groups who reported high and low levels of dispositional mindfulness skills were compared on a continuous measure of situational mindfulness skills. In Study 2 (N = 317), dispositional mindfulness questionnaires were used to predict situational use of mindfulness skills. Results suggest not only that situational measures accurately detect use of mindfulness skills, but also that dispositional measures can predict one\u27s use of situational mindfulness skills. Findings from both studies were consistent across both positive and negative situations. Moreover, neither neuroticism nor extraversion was shown to have a moderating effect on the relationship between dispositional and situational use of mindfulness skills. The implications of these findings for clinical practice and future investigations pertaining to measurement validity in this area are discussed

Processes That Contribute to Decreased Dimethyl Sulfide Production in Response to Ocean Acidification in Subtropical Waters

Long-term time series data show that ocean acidification is occurring in the subtropical oceans. As a component of an in situ mesocosm experiment carried out offGran Canaria in the subtropical North Atlantic, we examined the influence of ocean acidification on the net production of dimethylsulfide (DMS). Over 23 days under oligotrophic conditions, time-integrated DMS concentrations showed an inverse relationship of -0.21 ± 0.02 nmol DMS nmol-1 H+ across the gradient of H+ concentration of 8.8-23.3 nmol l-1, equivalent to a range of pCO2 of 400-1,252 atm. Proportionally similar decreases in the concentrations of both dissolved and particulate dimethylsulfoniopropionate (DMSP) were observed in relation to increasing H+ concentration between the mesocosms. The reduced net production of DMSP with increased acidity appeared to result from a decrease in abundance of a DMSP-rich nanophytoplankton population. A 35S-DMSP tracer approach was used to determine rates of dissolved DMSP catabolism, including DMS production, across the mesocosm treatments. Over a phase of increasing DMS concentrations during the experiment, the specific rates of DMS production were significantly reduced at elevated H+ concentration. These rates were closely correlated to the rates of net DMS production indicating that transformation of dissolved DMSP to DMS by bacteria was a major component of DMS production. It was not possible to resolve whether catabolism of DMSP was directly influenced by H+ concentrations or was an indirect response in the bacterial community composition associated with reduced DMSP availability. There is a pressing need to understand how subtropical planktonic communities respond to the predicted gradual prolonged ocean acidification, as alterations in the emission of DMS from the vast subtropical oceans could influence atmospheric chemistry and potentially climate, over a large proportion of the Earth's surface

Veliparib in Combination with Carboplatin and Etoposide in Patients with Treatment-Naive Extensive-Stage Small Cell Lung Cancer:A Phase 2 Randomized Study

Purpose: This study investigated the efficacy and safety of oral PARP inhibitor veliparib, plus carboplatin and etoposide in patients with treatment-naive, extensive-stage small cell lung cancer (ED-SCLC). Patients and Methods: Patients were randomized 1:1:1 to veliparib [240 mg twice daily (BID) for 14 days] plus chemotherapy followed by veliparib maintenance (400 mg BID; veliparib throughout), veliparib plus chemotherapy followed by placebo (veliparib combination only), or placebo plus chemotherapy followed by placebo (control). Patients received 4-6 cycles of combination therapy, then maintenance until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) with veliparib throughout versus control. Results: Overall (N = 181), PFS was improved with veliparib throughout versus control [hazard ratio (HR), 0.67; 80% confidence interval (CI), 0.50-0.88; P = 0.059]; median PFS was 5.8 and 5.6 months, respectively. There was a trend toward improved PFS with veliparib throughout versus control in SLFN11-positive patients (HR, 0.6; 80% CI, 0.36-0.97). Median overall survival (OS) was 10.1 versus 12.4 months in the veliparib throughout and control arms, respectively (HR, 1.43; 80% CI, 1.09-1.88). Grade 3/4 adverse events were experienced by 82%, 88%, and 68% of patients in the veliparib throughout, veliparib combination-only and control arms, most commonly hematologic. Conclusions: Veliparib plus platinum chemotherapy followed by veliparib maintenance demonstrated improved PFS as first-line treatment for ED-SCLC with an acceptable safety profile, but there was no corresponding benefit in OS. Further investigation is warranted to define the role of biomarkers in this setting

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Systemic Toll-Like Receptor Stimulation Suppresses Experimental Allergic Asthma and Autoimmune Diabetes in NOD Mice

BackgroundInfections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR) stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. Methods and Findings Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA)-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD) that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. Conclusions/Significance These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses. They provide a plausible explanation for the hygiene hypothesis. They also open new therapeutic perspectives for the prevention of these pathologies

Impaired neural processing of dynamic faces in left-onset Parkinson's disease

Parkinson's disease (PD) affects patients beyond the motor domain. According to previous evidence, one mechanism that may be impaired in the disease is face processing. However, few studies have investigated this process at the neural level in PD. Moreover, research using dynamic facial displays rather than static pictures is scarce, but highly warranted due to the higher ecological validity of dynamic stimuli. In the present study we aimed to investigate how PD patients process emotional and non-emotional dynamic face stimuli at the neural level using event-related potentials. Since the literature has revealed a predominantly right-lateralized network for dynamic face processing, we divided the group into patients with left (LPD) and right (RPD) motor symptom onset (right versus left cerebral hemisphere predominantly affected, respectively). Participants watched short video clips of happy, angry, and neutral expressions and engaged in a shallow gender decision task in order to avoid confounds of task difficulty in the data. In line with our expectations, the LPD group showed significant face processing deficits compared to controls. While there were no group differences in early, sensory-driven processing (fronto-central N1 and posterior P1), the vertex positive potential, which is considered the fronto-central counterpart of the face-specific posterior N170 component, had a reduced amplitude and delayed latency in the LPD group. This may indicate disturbances of structural face processing in LPD. Furthermore, the effect was independent of the emotional content of the videos. In contrast, static facial identity recognition performance in LPD was not significantly different from controls, and comprehensive testing of cognitive functions did not reveal any deficits in this group. We therefore conclude that PD, and more specifically the predominant right-hemispheric affection in left-onset PD, is associated with impaired processing of dynamic facial expressions, which could be one of the mechanisms behind the often reported problems of PD patients in their social lives

Measuring self-regulation in everyday life: reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Measuring self-regulation in everyday life: Reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one's goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test-retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures' construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Peptide Bβ15-42 Preserves Endothelial Barrier Function in Shock

Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn−/− mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock

Reconstruction versus conservative treatment after rupture of the anterior cruciate ligament: cost effectiveness analysis

BACKGROUND: The decision whether to treat conservatively or reconstruct surgically a torn anterior cruciate ligament (ACL) is an ongoing subject of debate. The high prevalence and associated public health burden of torn ACL has led to continuous efforts to determine the best therapeutic approach. A critical evaluation of benefits and expenditures of both treatment options as in a cost effectiveness analysis seems well-suited to provide valuable information for treating physicians and healthcare policymakers. METHODS: A literature review identified four of 7410 searched articles providing sufficient outcome probabilities for the two treatment options for modeling. A transformation key based on the expert opinions of 25 orthopedic surgeons was used to derive utilities from available evidence. The cost data for both treatment strategies were based on average figures compiled by Orthopaedic University Hospital Balgrist and reinforced by Swiss national statistics. A decision tree was constructed to derive the cost-effectiveness of each strategy, which was then tested for robustness using Monte Carlo simulation. RESULTS: Decision tree analysis revealed a cost effectiveness of 16,038 USD/0.78 QALY for ACL reconstruction and 15,466 USD/0.66 QALY for conservative treatment, implying an incremental cost effectiveness of 4,890 USD/QALY for ACL reconstruction. Sensitivity analysis of utilities did not change the trend. CONCLUSION: ACL reconstruction for reestablishment of knee stability seems cost effective in the Swiss setting based on currently available evidence. This, however, should be reinforced with randomized controlled trials comparing the two treatment strategies