Mind wandering and sleep in daily life: A combined actigraphy and experience sampling study.

Individuals who sleep poorly report spending more time mind wandering during the day. However, past research has relied on self-report measures of sleep or measured mind wandering during laboratory tasks, which prevents generalization to everyday contexts. We used ambulatory assessments to examine the relations between several features of sleep (duration, fragmentation, and disturbances) and mind wandering (task-unrelated, stimulus-independent, and unguided thoughts). Participants wore a wristband device that collected actigraphy and experience-sampling data across 7 days and 8 nights. Contrary to our expectations, task-unrelated and stimulus-independent thoughts were not associated with sleep either within- or between-persons (n = 164). Instead, individual differences in unguided thoughts were associated with sleep disturbances and duration, suggesting that individuals who more often experience unguided train-of-thoughts have greater sleep disturbances and sleep longer. These results highlight the need to consider the context and features of mind wandering when relating it to sleep.

Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design.

BACKGROUND: Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. METHODS: The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. DISCUSSION: The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.

Prospective links between social anxiety and adolescent peer relations.

This study examines bi-directional links between social anxiety and multiple aspects of peer relations (peer acceptance, peer victimization, and relationship quality) in a longitudinal sample of 1528 adolescents assessed twice with one year between (754 females and 774 males; M = 14.7 years of age). Lower levels of peer acceptance predicted increases in social anxiety. Social anxiety predicted decreases in relationship support for males and increases in peer victimization for females. Collectively our findings suggest that peers seem to play a significant role for adolescent mental health and social anxiety seems to interfere with healthy peer relations. Importantly, developmental pathways for social anxiety seem to differ for adolescent females and males.

The contribution of latent factors of executive functioning to mind wandering: an experience sampling study.

Accumulating evidence suggests that individuals with greater executive resources spend less time mind wandering. Independent strands of research further suggest that this association depends on concentration and a guilty-dysphoric daydreaming style. However, it remains unclear whether this association is specific to particular features of executive functioning or certain operationalizations of mind wandering, including task-unrelated thoughts (TUTs, comprising external distractions and mind wandering) and stimulus-independent and task-unrelated thoughts (SITUTs, comprising mind wandering only). This study sought to clarify these associations by using confirmatory factor analysis to compute latent scores for distinct executive functions based on nine cognitive tasks and relating them to experience sampling reports of mind wandering. We expected that individuals with greater executive control (specifically updating) would show a stronger reduction in SITUTs as momentary concentration and guilty-dysphoric style increase. A bifactor model of the cognitive battery indicated a general factor (common executive functioning) and ancillary factors (updating and shifting). A significant interaction between updating and concentration on mind wandering was observed with mind wandering defined as TUTs, but not as SITUTs (N = 187). A post hoc analysis clarified this discrepancy by showing that as concentration increases, both external distractions and mind wandering decrease more strongly among people with greater updating. Moreover, common executive functioning predicted a more negative slope of guilty-dysphoric style on SITUTs, whereas updating and shifting predicted more positive slopes. The opposite slopes of these executive functions on daily life mind wandering may reflect a stability-flexibility trade-off between goal maintenance and goal replacement abilities.

Sad mood and poor sleep are related to task-unrelated thoughts and experience of diminished cognitive control.

Previous studies have indicated that a sad mood and sleep deprivation increase mind wandering, but it is unclear whether these associations reflect reduced effort in concentrating on the task at hand or diminished cognitive control. In an internet-based experiment, participants completed a sleep disturbance questionnaire followed by a complex span task and a 2-back task with thought-sampling probes. Subsequently, participants underwent a positive, neutral, or negative mood induction prior to repeating the 2-back. The results (N = 504) replicated the finding of increased task-unrelated thoughts following sad mood induction, B = 0.56 (SE = 0.14), p < 0.01, d = 0.31. Unguided thoughts were increased following sad mood induction, B = 0.31 (0.13), p = 0.02, but working memory did not significantly moderate this association (p = 0.31). People reported a lower degree of trying to concentrate on the 2-back after the sad mood induction, B = -0.07 (0.04), p = 0.04, but actual performance was not affected (p = 0.46). Sleep disturbances showed small associations with task-unrelated, B = 0.23 (0.08), p < 0.01, and unguided thoughts, B = 0.32 (0.08), p < 0.01. This study strengthens the evidence that a sad mood and poor sleep relate to mind wandering.

Analyses of perch (Perca fluviatilis) bile suggest increasing exposure to PAHs and other pollutants in a reference area on the Swedish Baltic coast.

Kvädöfjärden on the Swedish Baltic coast has been used as a reference station in the Swedish National Marine Monitoring Programme since 1988. During this time an increasing trend in ethoxyresorufin-O-deetylase (EROD) activity and a decreasing trend in gonad size for female perch have been observed. It is known that EROD activity respond to exposure to certain groups of pollutants, including polycyclic aromatic hydrocarbons (PAHs). In the present study, perch bile from two years with high (2006) and low (2003) EROD levels, respectively, were analyzed. The concentration of PAH metabolites in bile was semi-quantified using fixed wavelength fluorescence. Furthermore, toxicity of the bile was tested on Daphnia magna. The total concentration of PAH metabolites and toxicity to D. magna was higher in 2006 than in 2003. Furthermore, there was a higher proportion of combustion-type PAHs in bile from 2006. The concentration of PAH metabolites in bile correlated to the EROD activity of the fish from which the bile was taken. There was no correlation between the concentrations of PAH metabolites and bile toxicity. Therefore, other pollutants than PAHs may also have been elevated in 2006. The results suggest that increasing exposure to PAHs can be causing the time trend in EROD activity. It is known that PAHs can have a negative effect on gonad development. Therefore, the decreasing trend in gonad size may also be caused by increasing exposure to PAHs.

Online validation of combined mood induction procedures.

Film clips, music, and self-referential statements (termed Velten, after their originator) have been successfully used to temporarily induce sadness and happiness. However, there is little research on the effectiveness of these procedures combined, particularly in internet-based settings, and whether Velten statements contribute to alter mood beyond the effect of simple instructions to close one's eyes and enter the targeted mood. In Study 1 (N = 106) we examined the effectiveness 80 Velten statements (positive, negative, neutral-self, neutral-facts) to create brief and effective sets that might be used in future research. In Study 2 (N = 445) we examined the effect size of 8-min combined mood induction procedures, which presented video clips in the first half and music excerpts with Velten statements or closed eyes instructions in the second half. Participants answered questionnaires on social desirability, joviality, and sadness before being randomly assigned to 1 of 7 groups varying in Valence (positive, negative, neutral) and Velten (closed eyes control, self-referential Velten, and, in the case of neutral condition, factual statements). Subsequently, participants completed the joviality and sadness scales a second time. Compared to the neutral conditions, the positive mood inductions increased joviality (Hedges G = 1.35, 95% CI [1.07, 1.63]), whereas the negative mood inductions increased sadness (Hedges G = 1.28, 95% CI [1.01, 1.55]). We did not observe any significant difference between Velten and closed eyes instructions in inducing joviality or sadness, nor did we observe any significant difference between neutral Velten statements referring to self and facts. Although social desirability bias was associated with reports of greater joviality and lower sadness, it could not account for the effects of the positive and negative mood induction procedures. We conclude that these combined mood induction procedures can be used in online research to study happy and sad mood.

Young voices in mental health care: Exploring children's and adolescents' service experiences and preferences.

The development of 'youth-friendly' services has become a priority across a wide range of health-care contexts. However, relatively few studies have specifically examined users' experiences of, and preferences for, child and adolescent mental health care. The current study investigated young service users' views of outpatient and community mental health clinics in Sweden, based on two data sources. First, focus group interviews were conducted with seven children and adolescents (aged 10-18 years) to explore both positive and negative experiences of mental health care. Second, written suggestions about specific service improvements were obtained from 106 children and adolescents. Qualitative content analysis revealed three overarching themes: 'Accessibility', 'Being heard and seen' and 'Usefulness of sessions'. Young people's recommendations for improving practice included more convenient appointment times, offered in welcoming settings; opportunities to communicate more openly with clinical staff, enabling sensitive discussion of mental health and wider personal issues; and more structured treatments that offer greater credibility and relevance to young people's mental health and developmental needs. Young people also discussed being compelled by parents and school professionals to engage in treatment. Attending to young people's preferences must be a priority in order to overcome ambivalence about session attendance, and enhance treatment participation and outcomes.

Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract.

To evaluate whether the organization of glutamatergic fibers systems in the lumbar cord is also evident at other spinal levels, we examined the immunocytochemical distribution of vesicle glutamate transporters 1 and 2 (VGLUT1, VGLUT2) at several different levels of the rat spinal cord. We also examined the expression of VGLUTs in an ascending sensory pathway, the spinocervical tract, and colocalization of VGLUT1 and VGLUT2. Mainly small VGLUT2-immunoreactive varicosities occurred at relatively high densities in most areas, with the highest density in laminae I-II. VGLUT1 immunolabeling, including small and medium-sized to large varicosities, was more differentiated, with the highest density in the deep dorsal horn and in certain nuclei such as the internal basilar nucleus, the central cervical nucleus, and the column of Clarke. Lamina I and IIo displayed a moderate density of small VGLUT1 varicosities at all spinal levels, although in the spinal enlargements a uniform density of such varicosities was evident throughout laminae I-II in the medial half of the dorsal horn. Corticospinal tract axons displayed VGLUT1, indicating that the corticospinal tract is an important source of small VGLUT1 varicosities. VGLUT1 and VGLUT2 were cocontained in small numbers of varicosities in laminae III-IV and IX. Anterogradely labeled spinocervical tract terminals in the lateral cervical nucleus were VGLUT2 immunoreactive. In conclusion, the principal distribution patterns of VGLUT1 and VGLUT2 are essentially similar throughout the rostrocaudal extension of the spinal cord. The mediolateral differences in VGLUT1 distribution in laminae I-II suggest dual origins of VGLUT1-immunoreactive varicosities in this region.

Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33°C vs 36°C After Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

IMPORTANCE: Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. OBJECTIVE: To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. INTERVENTIONS: Targeted temperature management at 33°C vs 36°C. MAIN OUTCOMES AND MEASURES: Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS: In the modified intent-to-treat population, including nonsurvivors, the median MMSE score was 14 in the 33°C group (interquartile range [IQR], 0-28) vs 17 in the 36°C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR, 79-130) vs 115 (IQR, 80-130) (P = .57) in the 33°C and 36°C groups, respectively. The median MMSE score for survivors was within the reference range and similar (33°C group median, 28; IQR, 26-30; vs 36°C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was within the minor deficit range (33°C group median, 79.5; IQR, 78.0-85.9; vs 36°C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs 17.5% of survivors reported needing help with everyday activities (P = .71), and 66.5% in the 33°C group vs 61.8% in the 36°C group reported that they thought they had made a complete mental recovery (P = .32). The mean (SD) mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P = .45), comparable to the population norm. CONCLUSIONS AND RELEVANCE: Quality of life was good and similar in patients with cardiac arrest receiving targeted temperature management at 33°C or 36°C. Cognitive function was similar in both intervention groups, but many patients and observers reported impairment not detected previously by standard outcome scales. TRIAL REGISTRATION: ClinicalTrials.gov NCT01020916.

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial.

BACKGROUND: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1. METHODS: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 10(6) cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. FINDINGS: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23,100 copies per mL Vacc-4x vs 71,800 copies per mL placebo; p=0·025) and week 52 (median 19,550 copies per mL vs 51,000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. INTERPRETATION: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. FUNDING: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.

Retrogradely transported fluorogold accumulates in lysosomes of neurons and is detectable ultrastructurally using post-embedding immuno-gold methods.

For ultrastructural studies, it is of great interest to be able to combine anatomical tracer techniques with sensitive immunohistochemical methods. Fluorogold (FG) is a fluorescent and retrogradely transported anatomical tracer, which is commonly used to label neurons in the brain and spinal cord for light microscopic studies. We here describe a method for detecting FG-labeled somata in the electron microscope using a high resolution post-embedding immuno-gold method. For this purpose, spinal motoneurons were retrogradely labeled by an intraperitoneal injection of FG in the adult rat. The rats were intravascularly perfused with a fixative solution containing 2% paraformaldehyde and 1-2% glutaraldehyde. Vibratome sections of spinal cord tissues were cryo-protected in glycerol, freeze substituted in methanol containing uranyl acetate, and embedded in the Lowicryl HM20 resin at low temperatures. Electron microscopic analysis demonstrated atypical lysosome-like structures in the cytoplasm of FG-labeled motoneurons. Subsequent post-embedding immuno-gold labeling demonstrated prominent accumulation of FG in numerous lysosomes but not in other organelles or cytoplasmic compartments of the labeled neurons. The protocol is versatile and allows for combining anatomical tracing of neurons with, e.g., neuro-transmitter studies in the electron microscope. We suggest that the described method for sensitive detection of FG in the spinal cord may also have broad applicability to other areas of the central nervous system.

Biosensor-based characterization of serum antibodies during development of an anti-IgE immunotherapeutic against allergy and asthma.

Antibody responses, induced in Cynomolgus monkey by recombinant IgE-derived immunotherapeutic protein against atopic allergies and asthma, were characterized using label-free, real-time protein interaction analysis. The effects of two different immunotherapeutic proteins were compared. Active concentrations of specific anti-IgE antibodies formed were determined in sera sampled at multiple time points, using conditions of total mass transport limitation that were proved to exist on the sensor surface. These concentrations varied from about 0.4 to 35 microg/ml among the monkeys and throughout the immunization period. Based on these concentrations, the rate and affinity constants for the binding of antibody populations to the antigen could be determined. The apparent equilibrium dissociation constant decreased during the immunization period, for all the monkeys, by a factor between 6 and 50, ending at values from approximately 2 x 10(-9) to approximately 2 x 10(-11) M among the animals. This affinity maturation was attributable to the changes in both rate constants, although the magnitude of the contribution of each constant depended partly on specimen, but primarily on the immunotherapeutic used. The immunotherapeutic proteins examined showed excellent immunogenic properties, providing the basis for a new and effective treatment for allergy and asthma.

Glutamate, but not aspartate, is enriched in trigeminothalamic tract terminals and associated with their synaptic vesicles in the rat nucleus submedius.

To examine the possible roles of glutamate and aspartate as neurotransmitters in the nucleus submedius (Sm) of rats, the distributions of these amino acids were examined by electron microscopic immunogold labeling. High levels of glutamate were detected in trigeminothalamic tract terminals anterogradely labeled with horseradish peroxidase conjugates. These terminals also displayed a positive correlation between the densities of synaptic vesicles and gold particles signaling glutamate. In contrast, aspartate levels in such terminals were low and displayed no correlation with the density of synaptic vesicles. Terminals of presumed cortical origin contained the highest estimated levels of glutamate, but the positive correlation between glutamate signal and synaptic vesicle density did not reach statistical significance, presumably due to technical factors. The latter terminals also contained relatively high levels of aspartate, though without any correlation to synaptic vesicle density. The present findings provide strong support for glutamate, but not aspartate, as a trigeminothalamic tract neurotransmitter responsible for the fast synaptic transmission of nociceptive signals to neurons in the rat nucleus submedius. Aspartate presumably serves metabolic roles in these terminals. With respect to terminals of presumed cortical origin, our data are not at odds with the notion that also these terminals use glutamate as their neurotransmitter. Our findings do not support a neurotransmitter role for aspartate in the latter terminals, although such a role cannot be entirely refuted.